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E. Brown-Myrie, Pharm. D. E. Brown-Myrie, Pharm. D. 1 CLINICAL PHARMACY CLINICAL PHARMACY AND THERAPEUTICS AND THERAPEUTICS HYPERTENSION HYPERTENSION
| Date post: | 28-Jan-2015 |
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Health & Medicine |
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E Brown-Myrie Pharm DE Brown-Myrie Pharm D 11
CLINICAL PHARMACY CLINICAL PHARMACY AND THERAPEUTICS AND THERAPEUTICS
HYPERTENSION HYPERTENSION
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 22
Introduction Introduction DefinitionDefinition An elevation of either the systolic blood pressure the diastolic An elevation of either the systolic blood pressure the diastolic
blood pressure or bothblood pressure or both
BP = CO x PVRBP = CO x PVR Hypertension is a sign of many underlying disease processes Hypertension is a sign of many underlying disease processes
the majority of which cause no symptomsthe majority of which cause no symptoms It is a major risk factor for the development of stroke renal It is a major risk factor for the development of stroke renal failure myocardial infarction and coronary artery diseasefailure myocardial infarction and coronary artery diseaseIt affects 10 ndash 15 of the worldrsquos population and often coexists It affects 10 ndash 15 of the worldrsquos population and often coexists with other disease conditions diabetes being the most with other disease conditions diabetes being the most
prevalentprevalent
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Blood Pressure Measurement and Clinical Blood Pressure Measurement and Clinical
EvaluationEvaluation (JNC VII)(JNC VII)
Classification and Management of Blood Pressure for Adults Classification and Management of Blood Pressure for Adults
BP ClassificationBP Classification Systolic (mm Hg)Systolic (mm Hg) Diastolic (mm Hg)Diastolic (mm Hg)
Normal Normal lt120lt120 and and lt80lt80
Prehypertension Prehypertension 120-139120-139 or or 80-8980-89
Hypertension Hypertension DaggerDagger
Stage 1Stage 1 140-159140-159 or or 90-9990-99
Stage 2Stage 2 gt gt 160160 or or gtgt 100 100
JNC7 = JNC7 = Seventh Report of the Joint National Committee on PreventionSeventh Report of the Joint National Committee on Prevention
Detection Evaluation and Treatment of High Blood PressureDetection Evaluation and Treatment of High Blood Pressure
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
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Recommendations for Follow-up Based on Initial Blood Recommendations for Follow-up Based on Initial Blood Pressure Measurements for Adults Pressure Measurements for Adults
Initial Blood Pressure (mm Hg)Initial Blood Pressure (mm Hg)
Systolic Systolic DiasstolicDiasstolic Follow-up Recommended Follow-up Recommended daggerdagger
lt130lt130 lt85lt85 Recheck in 2 yearsRecheck in 2 years
130-139130-139 85 ndash 8985 ndash 89 Recheck in 1 yearDaggerRecheck in 1 yearDagger
140-159140-159 90-9990-99 Confirm within 2 months DaggerConfirm within 2 months Dagger
160-179160-179 100-109100-109 Evaluate or refer to source of care Evaluate or refer to source of care within 1 monthwithin 1 month
gtgt180 180 gtgt 110 110 Evaluate or refer to source of care Evaluate or refer to source of care immediately or within 1 weekimmediately or within 1 week depending on clinical situation depending on clinical situation
If systolic and diastolic categories are different follow recommendations for shorter If systolic and diastolic categories are different follow recommendations for shorter time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care within 1 month)within 1 month)
dagger dagger Modify the scheduling of follow-up according to reliable information about past Modify the scheduling of follow-up according to reliable information about past blood pressure measurements other cardiovascular risk factors or target organ blood pressure measurements other cardiovascular risk factors or target organ disease disease
Dagger Dagger Provide advice about lifestyle modificationsProvide advice about lifestyle modifications
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Components of Cardiovascular Risk Stratification Components of Cardiovascular Risk Stratification in Patients with Hypertensionin Patients with Hypertension
Major Risk Factors Major Risk Factors SmokingSmoking Cigarette SmokingCigarette SmokingDyslipidemiaDyslipidemia Obesity (BMI gt 30 kgmObesity (BMI gt 30 kgm22
Diabetes MellitusDiabetes Mellitus Microalbuminuria or GFR lt 60 mLminMicroalbuminuria or GFR lt 60 mLminAge older than 55 for men 65 for womenAge older than 55 for men 65 for womenSex (men and postmenopausal women)Sex (men and postmenopausal women)Family history of cardiovascular disease women under age 65 or men Family history of cardiovascular disease women under age 65 or men under age 55under age 55
Target Organ DamageClinical Cardiovascular DiseaseTarget Organ DamageClinical Cardiovascular Disease
Heart DiseaseHeart DiseaseLeft ventricular hypertrophyLeft ventricular hypertrophy Nephropathy (CKD)Nephropathy (CKD)Anginaprior myocardial infarctionAnginaprior myocardial infarction Stroke or transient ischemic Stroke or transient ischemic
attackattackPrior coronary revascularizationPrior coronary revascularization Peripheral Arterial diseasePeripheral Arterial diseaseHeart failureHeart failure RetinopathyRetinopathy
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
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Risk Stratification and TreatmentRisk Stratification and Treatment
Blood Pressure Blood Pressure Lifestyle ModificationLifestyle Modification Drug therapy Drug therapy
Normal (lt12080)Normal (lt12080) EncourageEncourage Without Without With compellingWith compellingCompellingCompelling IndicationsIndicationsIndicationsIndications
Pre-hypertensionPre-hypertension YesYes No drug therapyNo drug therapy Drugs to treat com-Drugs to treat com-120-13980-89) 120-13980-89) pelling indicationspelling indications
Stage 1Stage 1 YesYes Thiazide-typeThiazide-type Drugs for the com-Drugs for the com-(140-15990-99)(140-15990-99) diuretics for mostdiuretics for most pelling indications pelling indications DaggerDagger
May use ACEIMay use ACEI Other agents (diureticsOther agents (diureticsARB BB CCBARB BB CCB ACE ARB BB CCBACE ARB BB CCBor combinationor combination as neededas needed
Stage 2 Stage 2 YesYes Two drugTwo drug As AboveAs Above((gtgt 160 160gtgt100)100) combinationcombination
for mostfor mostdaggerdagger
daggerdagger Initial combined therapy should be used cautiously in those at risk for orthostatic Initial combined therapy should be used cautiously in those at risk for orthostatic hypotensionhypotensionDaggerDagger Treat patients with chronic renal disease or diabetes to BP goal of lt13080Treat patients with chronic renal disease or diabetes to BP goal of lt13080
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
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EVALUATION amp EVALUATION amp DIAGNOSISDIAGNOSIS
Blood Pressure MeasurementBlood Pressure MeasurementComplete Medical HistoryComplete Medical HistoryPhysical ExaminationPhysical ExaminationLaboratory MeasurementsLaboratory Measurements
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BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
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COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
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LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
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MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
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Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
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Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
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Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
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Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
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Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
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Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
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E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
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Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
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Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
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Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
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Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
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Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
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Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 22
Introduction Introduction DefinitionDefinition An elevation of either the systolic blood pressure the diastolic An elevation of either the systolic blood pressure the diastolic
blood pressure or bothblood pressure or both
BP = CO x PVRBP = CO x PVR Hypertension is a sign of many underlying disease processes Hypertension is a sign of many underlying disease processes
the majority of which cause no symptomsthe majority of which cause no symptoms It is a major risk factor for the development of stroke renal It is a major risk factor for the development of stroke renal failure myocardial infarction and coronary artery diseasefailure myocardial infarction and coronary artery diseaseIt affects 10 ndash 15 of the worldrsquos population and often coexists It affects 10 ndash 15 of the worldrsquos population and often coexists with other disease conditions diabetes being the most with other disease conditions diabetes being the most
prevalentprevalent
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 33
Blood Pressure Measurement and Clinical Blood Pressure Measurement and Clinical
EvaluationEvaluation (JNC VII)(JNC VII)
Classification and Management of Blood Pressure for Adults Classification and Management of Blood Pressure for Adults
BP ClassificationBP Classification Systolic (mm Hg)Systolic (mm Hg) Diastolic (mm Hg)Diastolic (mm Hg)
Normal Normal lt120lt120 and and lt80lt80
Prehypertension Prehypertension 120-139120-139 or or 80-8980-89
Hypertension Hypertension DaggerDagger
Stage 1Stage 1 140-159140-159 or or 90-9990-99
Stage 2Stage 2 gt gt 160160 or or gtgt 100 100
JNC7 = JNC7 = Seventh Report of the Joint National Committee on PreventionSeventh Report of the Joint National Committee on Prevention
Detection Evaluation and Treatment of High Blood PressureDetection Evaluation and Treatment of High Blood Pressure
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 44
Recommendations for Follow-up Based on Initial Blood Recommendations for Follow-up Based on Initial Blood Pressure Measurements for Adults Pressure Measurements for Adults
Initial Blood Pressure (mm Hg)Initial Blood Pressure (mm Hg)
Systolic Systolic DiasstolicDiasstolic Follow-up Recommended Follow-up Recommended daggerdagger
lt130lt130 lt85lt85 Recheck in 2 yearsRecheck in 2 years
130-139130-139 85 ndash 8985 ndash 89 Recheck in 1 yearDaggerRecheck in 1 yearDagger
140-159140-159 90-9990-99 Confirm within 2 months DaggerConfirm within 2 months Dagger
160-179160-179 100-109100-109 Evaluate or refer to source of care Evaluate or refer to source of care within 1 monthwithin 1 month
gtgt180 180 gtgt 110 110 Evaluate or refer to source of care Evaluate or refer to source of care immediately or within 1 weekimmediately or within 1 week depending on clinical situation depending on clinical situation
If systolic and diastolic categories are different follow recommendations for shorter If systolic and diastolic categories are different follow recommendations for shorter time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care within 1 month)within 1 month)
dagger dagger Modify the scheduling of follow-up according to reliable information about past Modify the scheduling of follow-up according to reliable information about past blood pressure measurements other cardiovascular risk factors or target organ blood pressure measurements other cardiovascular risk factors or target organ disease disease
Dagger Dagger Provide advice about lifestyle modificationsProvide advice about lifestyle modifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 55
Components of Cardiovascular Risk Stratification Components of Cardiovascular Risk Stratification in Patients with Hypertensionin Patients with Hypertension
Major Risk Factors Major Risk Factors SmokingSmoking Cigarette SmokingCigarette SmokingDyslipidemiaDyslipidemia Obesity (BMI gt 30 kgmObesity (BMI gt 30 kgm22
Diabetes MellitusDiabetes Mellitus Microalbuminuria or GFR lt 60 mLminMicroalbuminuria or GFR lt 60 mLminAge older than 55 for men 65 for womenAge older than 55 for men 65 for womenSex (men and postmenopausal women)Sex (men and postmenopausal women)Family history of cardiovascular disease women under age 65 or men Family history of cardiovascular disease women under age 65 or men under age 55under age 55
Target Organ DamageClinical Cardiovascular DiseaseTarget Organ DamageClinical Cardiovascular Disease
Heart DiseaseHeart DiseaseLeft ventricular hypertrophyLeft ventricular hypertrophy Nephropathy (CKD)Nephropathy (CKD)Anginaprior myocardial infarctionAnginaprior myocardial infarction Stroke or transient ischemic Stroke or transient ischemic
attackattackPrior coronary revascularizationPrior coronary revascularization Peripheral Arterial diseasePeripheral Arterial diseaseHeart failureHeart failure RetinopathyRetinopathy
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D66
Risk Stratification and TreatmentRisk Stratification and Treatment
Blood Pressure Blood Pressure Lifestyle ModificationLifestyle Modification Drug therapy Drug therapy
Normal (lt12080)Normal (lt12080) EncourageEncourage Without Without With compellingWith compellingCompellingCompelling IndicationsIndicationsIndicationsIndications
Pre-hypertensionPre-hypertension YesYes No drug therapyNo drug therapy Drugs to treat com-Drugs to treat com-120-13980-89) 120-13980-89) pelling indicationspelling indications
Stage 1Stage 1 YesYes Thiazide-typeThiazide-type Drugs for the com-Drugs for the com-(140-15990-99)(140-15990-99) diuretics for mostdiuretics for most pelling indications pelling indications DaggerDagger
May use ACEIMay use ACEI Other agents (diureticsOther agents (diureticsARB BB CCBARB BB CCB ACE ARB BB CCBACE ARB BB CCBor combinationor combination as neededas needed
Stage 2 Stage 2 YesYes Two drugTwo drug As AboveAs Above((gtgt 160 160gtgt100)100) combinationcombination
for mostfor mostdaggerdagger
daggerdagger Initial combined therapy should be used cautiously in those at risk for orthostatic Initial combined therapy should be used cautiously in those at risk for orthostatic hypotensionhypotensionDaggerDagger Treat patients with chronic renal disease or diabetes to BP goal of lt13080Treat patients with chronic renal disease or diabetes to BP goal of lt13080
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 77
EVALUATION amp EVALUATION amp DIAGNOSISDIAGNOSIS
Blood Pressure MeasurementBlood Pressure MeasurementComplete Medical HistoryComplete Medical HistoryPhysical ExaminationPhysical ExaminationLaboratory MeasurementsLaboratory Measurements
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 88
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 33
Blood Pressure Measurement and Clinical Blood Pressure Measurement and Clinical
EvaluationEvaluation (JNC VII)(JNC VII)
Classification and Management of Blood Pressure for Adults Classification and Management of Blood Pressure for Adults
BP ClassificationBP Classification Systolic (mm Hg)Systolic (mm Hg) Diastolic (mm Hg)Diastolic (mm Hg)
Normal Normal lt120lt120 and and lt80lt80
Prehypertension Prehypertension 120-139120-139 or or 80-8980-89
Hypertension Hypertension DaggerDagger
Stage 1Stage 1 140-159140-159 or or 90-9990-99
Stage 2Stage 2 gt gt 160160 or or gtgt 100 100
JNC7 = JNC7 = Seventh Report of the Joint National Committee on PreventionSeventh Report of the Joint National Committee on Prevention
Detection Evaluation and Treatment of High Blood PressureDetection Evaluation and Treatment of High Blood Pressure
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 44
Recommendations for Follow-up Based on Initial Blood Recommendations for Follow-up Based on Initial Blood Pressure Measurements for Adults Pressure Measurements for Adults
Initial Blood Pressure (mm Hg)Initial Blood Pressure (mm Hg)
Systolic Systolic DiasstolicDiasstolic Follow-up Recommended Follow-up Recommended daggerdagger
lt130lt130 lt85lt85 Recheck in 2 yearsRecheck in 2 years
130-139130-139 85 ndash 8985 ndash 89 Recheck in 1 yearDaggerRecheck in 1 yearDagger
140-159140-159 90-9990-99 Confirm within 2 months DaggerConfirm within 2 months Dagger
160-179160-179 100-109100-109 Evaluate or refer to source of care Evaluate or refer to source of care within 1 monthwithin 1 month
gtgt180 180 gtgt 110 110 Evaluate or refer to source of care Evaluate or refer to source of care immediately or within 1 weekimmediately or within 1 week depending on clinical situation depending on clinical situation
If systolic and diastolic categories are different follow recommendations for shorter If systolic and diastolic categories are different follow recommendations for shorter time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care within 1 month)within 1 month)
dagger dagger Modify the scheduling of follow-up according to reliable information about past Modify the scheduling of follow-up according to reliable information about past blood pressure measurements other cardiovascular risk factors or target organ blood pressure measurements other cardiovascular risk factors or target organ disease disease
Dagger Dagger Provide advice about lifestyle modificationsProvide advice about lifestyle modifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 55
Components of Cardiovascular Risk Stratification Components of Cardiovascular Risk Stratification in Patients with Hypertensionin Patients with Hypertension
Major Risk Factors Major Risk Factors SmokingSmoking Cigarette SmokingCigarette SmokingDyslipidemiaDyslipidemia Obesity (BMI gt 30 kgmObesity (BMI gt 30 kgm22
Diabetes MellitusDiabetes Mellitus Microalbuminuria or GFR lt 60 mLminMicroalbuminuria or GFR lt 60 mLminAge older than 55 for men 65 for womenAge older than 55 for men 65 for womenSex (men and postmenopausal women)Sex (men and postmenopausal women)Family history of cardiovascular disease women under age 65 or men Family history of cardiovascular disease women under age 65 or men under age 55under age 55
Target Organ DamageClinical Cardiovascular DiseaseTarget Organ DamageClinical Cardiovascular Disease
Heart DiseaseHeart DiseaseLeft ventricular hypertrophyLeft ventricular hypertrophy Nephropathy (CKD)Nephropathy (CKD)Anginaprior myocardial infarctionAnginaprior myocardial infarction Stroke or transient ischemic Stroke or transient ischemic
attackattackPrior coronary revascularizationPrior coronary revascularization Peripheral Arterial diseasePeripheral Arterial diseaseHeart failureHeart failure RetinopathyRetinopathy
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D66
Risk Stratification and TreatmentRisk Stratification and Treatment
Blood Pressure Blood Pressure Lifestyle ModificationLifestyle Modification Drug therapy Drug therapy
Normal (lt12080)Normal (lt12080) EncourageEncourage Without Without With compellingWith compellingCompellingCompelling IndicationsIndicationsIndicationsIndications
Pre-hypertensionPre-hypertension YesYes No drug therapyNo drug therapy Drugs to treat com-Drugs to treat com-120-13980-89) 120-13980-89) pelling indicationspelling indications
Stage 1Stage 1 YesYes Thiazide-typeThiazide-type Drugs for the com-Drugs for the com-(140-15990-99)(140-15990-99) diuretics for mostdiuretics for most pelling indications pelling indications DaggerDagger
May use ACEIMay use ACEI Other agents (diureticsOther agents (diureticsARB BB CCBARB BB CCB ACE ARB BB CCBACE ARB BB CCBor combinationor combination as neededas needed
Stage 2 Stage 2 YesYes Two drugTwo drug As AboveAs Above((gtgt 160 160gtgt100)100) combinationcombination
for mostfor mostdaggerdagger
daggerdagger Initial combined therapy should be used cautiously in those at risk for orthostatic Initial combined therapy should be used cautiously in those at risk for orthostatic hypotensionhypotensionDaggerDagger Treat patients with chronic renal disease or diabetes to BP goal of lt13080Treat patients with chronic renal disease or diabetes to BP goal of lt13080
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 77
EVALUATION amp EVALUATION amp DIAGNOSISDIAGNOSIS
Blood Pressure MeasurementBlood Pressure MeasurementComplete Medical HistoryComplete Medical HistoryPhysical ExaminationPhysical ExaminationLaboratory MeasurementsLaboratory Measurements
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 88
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 44
Recommendations for Follow-up Based on Initial Blood Recommendations for Follow-up Based on Initial Blood Pressure Measurements for Adults Pressure Measurements for Adults
Initial Blood Pressure (mm Hg)Initial Blood Pressure (mm Hg)
Systolic Systolic DiasstolicDiasstolic Follow-up Recommended Follow-up Recommended daggerdagger
lt130lt130 lt85lt85 Recheck in 2 yearsRecheck in 2 years
130-139130-139 85 ndash 8985 ndash 89 Recheck in 1 yearDaggerRecheck in 1 yearDagger
140-159140-159 90-9990-99 Confirm within 2 months DaggerConfirm within 2 months Dagger
160-179160-179 100-109100-109 Evaluate or refer to source of care Evaluate or refer to source of care within 1 monthwithin 1 month
gtgt180 180 gtgt 110 110 Evaluate or refer to source of care Evaluate or refer to source of care immediately or within 1 weekimmediately or within 1 week depending on clinical situation depending on clinical situation
If systolic and diastolic categories are different follow recommendations for shorter If systolic and diastolic categories are different follow recommendations for shorter time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care time follow-up (eg 16086 mm Hg should be evaluated or referred to source of care within 1 month)within 1 month)
dagger dagger Modify the scheduling of follow-up according to reliable information about past Modify the scheduling of follow-up according to reliable information about past blood pressure measurements other cardiovascular risk factors or target organ blood pressure measurements other cardiovascular risk factors or target organ disease disease
Dagger Dagger Provide advice about lifestyle modificationsProvide advice about lifestyle modifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 55
Components of Cardiovascular Risk Stratification Components of Cardiovascular Risk Stratification in Patients with Hypertensionin Patients with Hypertension
Major Risk Factors Major Risk Factors SmokingSmoking Cigarette SmokingCigarette SmokingDyslipidemiaDyslipidemia Obesity (BMI gt 30 kgmObesity (BMI gt 30 kgm22
Diabetes MellitusDiabetes Mellitus Microalbuminuria or GFR lt 60 mLminMicroalbuminuria or GFR lt 60 mLminAge older than 55 for men 65 for womenAge older than 55 for men 65 for womenSex (men and postmenopausal women)Sex (men and postmenopausal women)Family history of cardiovascular disease women under age 65 or men Family history of cardiovascular disease women under age 65 or men under age 55under age 55
Target Organ DamageClinical Cardiovascular DiseaseTarget Organ DamageClinical Cardiovascular Disease
Heart DiseaseHeart DiseaseLeft ventricular hypertrophyLeft ventricular hypertrophy Nephropathy (CKD)Nephropathy (CKD)Anginaprior myocardial infarctionAnginaprior myocardial infarction Stroke or transient ischemic Stroke or transient ischemic
attackattackPrior coronary revascularizationPrior coronary revascularization Peripheral Arterial diseasePeripheral Arterial diseaseHeart failureHeart failure RetinopathyRetinopathy
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D66
Risk Stratification and TreatmentRisk Stratification and Treatment
Blood Pressure Blood Pressure Lifestyle ModificationLifestyle Modification Drug therapy Drug therapy
Normal (lt12080)Normal (lt12080) EncourageEncourage Without Without With compellingWith compellingCompellingCompelling IndicationsIndicationsIndicationsIndications
Pre-hypertensionPre-hypertension YesYes No drug therapyNo drug therapy Drugs to treat com-Drugs to treat com-120-13980-89) 120-13980-89) pelling indicationspelling indications
Stage 1Stage 1 YesYes Thiazide-typeThiazide-type Drugs for the com-Drugs for the com-(140-15990-99)(140-15990-99) diuretics for mostdiuretics for most pelling indications pelling indications DaggerDagger
May use ACEIMay use ACEI Other agents (diureticsOther agents (diureticsARB BB CCBARB BB CCB ACE ARB BB CCBACE ARB BB CCBor combinationor combination as neededas needed
Stage 2 Stage 2 YesYes Two drugTwo drug As AboveAs Above((gtgt 160 160gtgt100)100) combinationcombination
for mostfor mostdaggerdagger
daggerdagger Initial combined therapy should be used cautiously in those at risk for orthostatic Initial combined therapy should be used cautiously in those at risk for orthostatic hypotensionhypotensionDaggerDagger Treat patients with chronic renal disease or diabetes to BP goal of lt13080Treat patients with chronic renal disease or diabetes to BP goal of lt13080
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
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EVALUATION amp EVALUATION amp DIAGNOSISDIAGNOSIS
Blood Pressure MeasurementBlood Pressure MeasurementComplete Medical HistoryComplete Medical HistoryPhysical ExaminationPhysical ExaminationLaboratory MeasurementsLaboratory Measurements
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 88
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
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Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
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Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 55
Components of Cardiovascular Risk Stratification Components of Cardiovascular Risk Stratification in Patients with Hypertensionin Patients with Hypertension
Major Risk Factors Major Risk Factors SmokingSmoking Cigarette SmokingCigarette SmokingDyslipidemiaDyslipidemia Obesity (BMI gt 30 kgmObesity (BMI gt 30 kgm22
Diabetes MellitusDiabetes Mellitus Microalbuminuria or GFR lt 60 mLminMicroalbuminuria or GFR lt 60 mLminAge older than 55 for men 65 for womenAge older than 55 for men 65 for womenSex (men and postmenopausal women)Sex (men and postmenopausal women)Family history of cardiovascular disease women under age 65 or men Family history of cardiovascular disease women under age 65 or men under age 55under age 55
Target Organ DamageClinical Cardiovascular DiseaseTarget Organ DamageClinical Cardiovascular Disease
Heart DiseaseHeart DiseaseLeft ventricular hypertrophyLeft ventricular hypertrophy Nephropathy (CKD)Nephropathy (CKD)Anginaprior myocardial infarctionAnginaprior myocardial infarction Stroke or transient ischemic Stroke or transient ischemic
attackattackPrior coronary revascularizationPrior coronary revascularization Peripheral Arterial diseasePeripheral Arterial diseaseHeart failureHeart failure RetinopathyRetinopathy
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D66
Risk Stratification and TreatmentRisk Stratification and Treatment
Blood Pressure Blood Pressure Lifestyle ModificationLifestyle Modification Drug therapy Drug therapy
Normal (lt12080)Normal (lt12080) EncourageEncourage Without Without With compellingWith compellingCompellingCompelling IndicationsIndicationsIndicationsIndications
Pre-hypertensionPre-hypertension YesYes No drug therapyNo drug therapy Drugs to treat com-Drugs to treat com-120-13980-89) 120-13980-89) pelling indicationspelling indications
Stage 1Stage 1 YesYes Thiazide-typeThiazide-type Drugs for the com-Drugs for the com-(140-15990-99)(140-15990-99) diuretics for mostdiuretics for most pelling indications pelling indications DaggerDagger
May use ACEIMay use ACEI Other agents (diureticsOther agents (diureticsARB BB CCBARB BB CCB ACE ARB BB CCBACE ARB BB CCBor combinationor combination as neededas needed
Stage 2 Stage 2 YesYes Two drugTwo drug As AboveAs Above((gtgt 160 160gtgt100)100) combinationcombination
for mostfor mostdaggerdagger
daggerdagger Initial combined therapy should be used cautiously in those at risk for orthostatic Initial combined therapy should be used cautiously in those at risk for orthostatic hypotensionhypotensionDaggerDagger Treat patients with chronic renal disease or diabetes to BP goal of lt13080Treat patients with chronic renal disease or diabetes to BP goal of lt13080
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 77
EVALUATION amp EVALUATION amp DIAGNOSISDIAGNOSIS
Blood Pressure MeasurementBlood Pressure MeasurementComplete Medical HistoryComplete Medical HistoryPhysical ExaminationPhysical ExaminationLaboratory MeasurementsLaboratory Measurements
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 88
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D66
Risk Stratification and TreatmentRisk Stratification and Treatment
Blood Pressure Blood Pressure Lifestyle ModificationLifestyle Modification Drug therapy Drug therapy
Normal (lt12080)Normal (lt12080) EncourageEncourage Without Without With compellingWith compellingCompellingCompelling IndicationsIndicationsIndicationsIndications
Pre-hypertensionPre-hypertension YesYes No drug therapyNo drug therapy Drugs to treat com-Drugs to treat com-120-13980-89) 120-13980-89) pelling indicationspelling indications
Stage 1Stage 1 YesYes Thiazide-typeThiazide-type Drugs for the com-Drugs for the com-(140-15990-99)(140-15990-99) diuretics for mostdiuretics for most pelling indications pelling indications DaggerDagger
May use ACEIMay use ACEI Other agents (diureticsOther agents (diureticsARB BB CCBARB BB CCB ACE ARB BB CCBACE ARB BB CCBor combinationor combination as neededas needed
Stage 2 Stage 2 YesYes Two drugTwo drug As AboveAs Above((gtgt 160 160gtgt100)100) combinationcombination
for mostfor mostdaggerdagger
daggerdagger Initial combined therapy should be used cautiously in those at risk for orthostatic Initial combined therapy should be used cautiously in those at risk for orthostatic hypotensionhypotensionDaggerDagger Treat patients with chronic renal disease or diabetes to BP goal of lt13080Treat patients with chronic renal disease or diabetes to BP goal of lt13080
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 77
EVALUATION amp EVALUATION amp DIAGNOSISDIAGNOSIS
Blood Pressure MeasurementBlood Pressure MeasurementComplete Medical HistoryComplete Medical HistoryPhysical ExaminationPhysical ExaminationLaboratory MeasurementsLaboratory Measurements
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 88
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 77
EVALUATION amp EVALUATION amp DIAGNOSISDIAGNOSIS
Blood Pressure MeasurementBlood Pressure MeasurementComplete Medical HistoryComplete Medical HistoryPhysical ExaminationPhysical ExaminationLaboratory MeasurementsLaboratory Measurements
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 88
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 88
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTSMEASUREMENTS
Use properly calibrated and validated Use properly calibrated and validated instrumentinstrument
Patient should be seated quietly for at least 5 Patient should be seated quietly for at least 5 minutesminutes
Use appropriate size cuff (cuff bladder encircles Use appropriate size cuff (cuff bladder encircles at least 80 of arm)at least 80 of arm)
At least two measurements should be madeAt least two measurements should be made SBP is the first sound heard DBP is the point SBP is the first sound heard DBP is the point
before disappearance of soundsbefore disappearance of sounds
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 99
COMPLETE MEDICAL HISTORYCOMPLETE MEDICAL HISTORY
Known duration and level of elevated BPKnown duration and level of elevated BP History or symptoms of CHD HF CVA History or symptoms of CHD HF CVA
peripheral vascular disease DM dyslipidemia peripheral vascular disease DM dyslipidemia renal diseaserenal disease
Family history of CV disease DM etcFamily history of CV disease DM etc History of recent changes in weightHistory of recent changes in weight Dietary assessment- Na alcohol intakeDietary assessment- Na alcohol intake History of prescribed and over-the-counter History of prescribed and over-the-counter
drugsdrugs
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
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E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1010
PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
Fundoscopic examination (arteriolar narrowing focal Fundoscopic examination (arteriolar narrowing focal arteriolar constrictions AV nicking hemorrhages exudates arteriolar constrictions AV nicking hemorrhages exudates and disc edema)and disc edema)Neck examination (carotid bruits distended veins enlarged Neck examination (carotid bruits distended veins enlarged thyroid)thyroid)Heart (abnormal rates amp rhythms increased size murmurs Heart (abnormal rates amp rhythms increased size murmurs third and fourth sounds)third and fourth sounds)Lung (rales evidence of bronchospasm)Lung (rales evidence of bronchospasm)Abdomen (bruits enlarged kidneys masses abnormal Abdomen (bruits enlarged kidneys masses abnormal aortic pulses)aortic pulses)Extremities (diminished or absent peripheral pulsesbruits Extremities (diminished or absent peripheral pulsesbruits and edema)and edema)
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LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
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MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
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Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
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Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
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Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
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Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
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E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
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Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
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VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1111
LABORATORY MEASUREMENTSLABORATORY MEASUREMENTS
UrinalysisUrinalysis Complete Blood CountComplete Blood Count Blood chemistryBlood chemistry ElectrocardiogramElectrocardiogram
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
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Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
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VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
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Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
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RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1212
MANAGEMENT OF MANAGEMENT OF HYPERTENSIONHYPERTENSION
Goals of TherapyGoals of Therapy
Lifestyle ModificationsLifestyle Modifications
Pharmacologic TreatmentPharmacologic Treatment
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
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Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
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Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
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Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
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E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
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Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1313
Goals of TherapyGoals of Therapy
Reduce cardiovascular and renal Reduce cardiovascular and renal morbidity and mortalitymorbidity and mortality
Achieve and maintain SBP below 140 mm Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm HgHg and DBP below 90 mm Hg DiabetesDiabetes lt13080lt13080 RFHFRFHF lt13080lt13080
Control modifiable risk factors for CV Control modifiable risk factors for CV diseasedisease
Hypertension 2003421206ndash1252Hypertension 2003421206ndash1252
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target(mm Hg)
General CADPrevention
lt14090
High CAD risk lt13080
CAD
LVD
lt13080
lt12080
Circulation 20071152761-2788E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1414
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
2007 ndash AHA Scientific 2007 ndash AHA Scientific StatementStatement
AREA BP Target (mm Hg) Specific Drug Indications
General CADPrevention
lt14090 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
High CAD risk
lt13080 Monotherapy or combination therapybull ACEI (or ARB) CCB or thiazidediuretic first-line
CAD
LVD
lt13080
lt12080
β-blocker and ACEI or ARB
ACEI or ARB and β-blocker andaldosterone antagonist and diuretic
Circulation 20071152761-2788
1515
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1616
Lifestyle Modifications to Manage Lifestyle Modifications to Manage HypertensionHypertension
Weight Reduction (BMI 185 ndash 249 kgmWeight Reduction (BMI 185 ndash 249 kgm22)) Adopt DASH (Dietary Approaches to Stop Adopt DASH (Dietary Approaches to Stop
Hypertension) Eating PlanHypertension) Eating Plan Increase Aerobic ExerciseIncrease Aerobic Exercise Reduce Sodium intake to no more than 100 Reduce Sodium intake to no more than 100
mmolday (24 g sodium or 6 grams NaCl)mmolday (24 g sodium or 6 grams NaCl) Limit consumption of alcohol to 1 oz or 30 mL Limit consumption of alcohol to 1 oz or 30 mL
ethanol (24 oz beer10 oz wineetc)ethanol (24 oz beer10 oz wineetc) Stop smokingStop smoking
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
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Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1717
PHARMACOLOGIC TREATMENTPHARMACOLOGIC TREATMENT
General GuidelinesGeneral Guidelines Use low dose of antihypertensive and Use low dose of antihypertensive and
titrate up slowlytitrate up slowly Optimal formulation should provide 24 Optimal formulation should provide 24
hour efficacy with once daily dosehour efficacy with once daily dose Long acting formulations are preferredLong acting formulations are preferred Low dose combinations provide additional Low dose combinations provide additional
antihypertensive efficacyantihypertensive efficacy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1818
Treatment - Special ConsiderationsTreatment - Special Considerations
Demographics ndash Blacks respond better to Demographics ndash Blacks respond better to diuretics amp CCBsdiuretics amp CCBs
Concomitant Diseases and Therapies ndash Concomitant Diseases and Therapies ndash antihypertensives may worsen or improve antihypertensives may worsen or improve coexisting conditioncoexisting condition
Quality of Life ndash antihypertensives used should Quality of Life ndash antihypertensives used should improve quality of life (watch adverse effects)improve quality of life (watch adverse effects)
Cost ndash cost may be a barrier to BP control Cost ndash cost may be a barrier to BP control (consider generics)(consider generics)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 1919
Treatment RecommendationsTreatment Recommendations
Several classes of drugs (ACEIs ARBs BBs Several classes of drugs (ACEIs ARBs BBs CCBs and thiazide-type diuretics will reduce CCBs and thiazide-type diuretics will reduce complications of hypertensioncomplications of hypertension
Thiazide-type diuretics have been supported in Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTNpreventing cardiovascular complications of HTN
Thiazide-type diuretics should be used as initial Thiazide-type diuretics should be used as initial therapy for most patients with hypertension therapy for most patients with hypertension (either alone or in combination)(either alone or in combination)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2020
Treatment Recommendations contTreatment Recommendations cont
Concomittant diseases (compelling Concomittant diseases (compelling indications) may require use of other indications) may require use of other antihypertensives as initial therapyantihypertensives as initial therapy
Where a drug is contraindicated or not Where a drug is contraindicated or not tolerated another class with proven tolerated another class with proven efficacy should be usedefficacy should be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2121
Clinical Trial amp Guideline Basis for Clinical Trial amp Guideline Basis for compelling Indications for Drug Therapycompelling Indications for Drug Therapy
Compelling Compelling IndicationIndication
DiurDiureticetic
BBBB ACACEIEI
ARBARB CCBCCB Aldo Aldo ANTANT
Clinical Trials BasisClinical Trials Basis
Heart FailureHeart Failure bullbull bullbull bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines MERIT-HF Guidelines MERIT-HF COPERNICUSCIBIS COPERNICUSCIBIS SOLVDAIRE TRACE SOLVDAIRE TRACE ValHEFTRALESValHEFTRALES
Post MIPost MI bullbull bullbull bullbull ACCAHA Heart Failure ACCAHA Heart Failure Guidelines BHAT SAVE Guidelines BHAT SAVE Capricorn EPHESUSCapricorn EPHESUS
High Coronary High Coronary disease riskdisease risk
bullbull bullbull bullbull bullbull ALLHAT HOPE ANBP2 ALLHAT HOPE ANBP2 LIFECONVINCELIFECONVINCE
DiabetesDiabetes bullbull bullbull bullbull bullbull bullbull NKF-ADA Guideline UKPDS NKF-ADA Guideline UKPDS ALLHAT ALLHAT
Chronic Kidney Chronic Kidney diseasedisease
bullbull bullbull NKF Guideline Captopril Trial NKF Guideline Captopril Trial RENAALIDNTREIN AASKRENAALIDNTREIN AASK
Recurrent stroke Recurrent stroke prevention prevention
bullbull bullbull PROGRESSPROGRESS
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
Study AbbreviationsStudy Abbreviations AASKAASK African American Study of Kidney Disease amp African American Study of Kidney Disease amp
HypertensionHypertension ACCAHA ACCAHA American College of CardiologyAmerican American College of CardiologyAmerican
Heart Heart AssociationAssociation AIREAIRE Acute Infarction Ramipril EfficacyAcute Infarction Ramipril Efficacy ALLHATALLHAT Antihypertensive and Lipid Lowering Antihypertensive and Lipid Lowering
Treatment Treatment to Prevent Heart Attack Trialto Prevent Heart Attack Trial ANBP2 ANBP2 Second Australian National Blood Second Australian National Blood
Pressure StudyPressure Study BHATBHAT Beta Blocker Haert Attack TrialBeta Blocker Haert Attack Trial CIBISCIBIS Cardiac Insufficiency Bisoprolol StudyCardiac Insufficiency Bisoprolol Study CONVINCE Controlled Onset Verapamil Investigation CONVINCE Controlled Onset Verapamil Investigation
of Cardiovascular Endpoints of Cardiovascular EndpointsE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2222
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
Study AbbreviationsStudy Abbreviations
COPERNICUS ndashCarvedilol Prospective COPERNICUS ndashCarvedilol Prospective Randomized Randomized Cumulative Cumulative Survival StudySurvival Study
EPHESUSEPHESUS Eplerenone Post-Acute Myocardial Eplerenone Post-Acute Myocardial Infarction Heart Failure Infarction Heart Failure
Efficacy and Efficacy and Survival StudySurvival Study HOPEHOPE Heart Outcomes Prevention Heart Outcomes Prevention
Evaluation Evaluation StudyStudy IDNTIDNT Irbesartan Diabetic Nephropathy TrialIrbesartan Diabetic Nephropathy Trial LIFELIFE Losartan Intervention for Endpoint Losartan Intervention for Endpoint
Reduction in Hypertension StudyReduction in Hypertension StudyE Brown-Myrie Pharm DE Brown-Myrie Pharm D 2323
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
Study AbbreviationsStudy Abbreviations MERIT-HFMERIT-HF Metoprolol CRXL Randomized Metoprolol CRXL Randomized
Intervention Trial in Congestive Intervention Trial in Congestive Heart FailureHeart Failure
NKF-ADANKF-ADA National Kidney Foundation-National Kidney Foundation-AmericReduction an AmericReduction an
Diabetes AssociationDiabetes Association PROGRESSPROGRESS Perindopril Protection Against Perindopril Protection Against
Recurrent Stroke StudyRecurrent Stroke Study RALESRALES Randomized Aldactone Evaluation StudyRandomized Aldactone Evaluation Study REINREIN RamiprilEfficacy in Nephropathy Study RamiprilEfficacy in Nephropathy Study RENAALRENAAL of Endpoints in Non Insulin of Endpoints in Non Insulin
Dependent Dependent Diabetes Mellitus With the Diabetes Mellitus With the Angiotensin II Angiotensin II Antagonist Losartan Antagonist Losartan StudyStudy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2424
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
Study AbbreviationsStudy Abbreviations
SAVESAVE Survival and Ventricular Enlargement Survival and Ventricular Enlargement StudyStudy
SOLVDSOLVD Studies of Left Ventricular Studies of Left Ventricular DysfunctionDysfunction
TRACETRACE Trandolapril Cardiac Evaluation Trandolapril Cardiac Evaluation StudyStudy
UKPDSUKPDS United Kingdom Prospective United Kingdom Prospective Diabetes Diabetes StudyStudy
ValHEFT Valsartan Heart Failure TrialValHEFT Valsartan Heart Failure Trial
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2525
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2626
Special Considerations- Black Special Considerations- Black PatientsPatients
There is increased prevalence severity and There is increased prevalence severity and impact of HTN in black patientsimpact of HTN in black patients
Blacks show reduced responsiveness to ACEIs Blacks show reduced responsiveness to ACEIs BBs and ARBs compared to diuretics and CCBsBBs and ARBs compared to diuretics and CCBs
Reduced responsiveness may be improved with Reduced responsiveness may be improved with drug combinations especially those including drug combinations especially those including diureticsdiuretics
ACEI ndash induced angio-edema may be more ACEI ndash induced angio-edema may be more common in blacks than any other groupcommon in blacks than any other group
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2727
Special Considerations ndash Elderly Special Considerations ndash Elderly PatientsPatients
HTN is very common in elderly SBP is better HTN is very common in elderly SBP is better predictor of CV events and all cause mortalitypredictor of CV events and all cause mortality
Some older patients exhibit pseudo-Some older patients exhibit pseudo-hypertension due to excessive vascular hypertension due to excessive vascular stiffnessstiffness
HTN therapy should begin with lifestyle HTN therapy should begin with lifestyle modificationsmodifications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2828
Special Considerations ndash Elderly Special Considerations ndash Elderly Patients contPatients cont
When pharmacologic treatment is used the When pharmacologic treatment is used the dose should be reduced by halfdose should be reduced by half
Thiazide diuretics or BBs in combination with Thiazide diuretics or BBs in combination with thiazides are recommended initial therapythiazides are recommended initial therapy
Diuretics are preferred in isolated systolic Diuretics are preferred in isolated systolic hypertensionhypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 2929
Special Considerations- Young Special Considerations- Young PatientsPatients
Lifestyle modification should be first Lifestyle modification should be first recommendationrecommendation
Recommendations for choice of drugs are Recommendations for choice of drugs are the same as for adults but dosages the same as for adults but dosages should be smaller and adjusted should be smaller and adjusted appropriatelyappropriately
ACEIs and ARBs should not be used in ACEIs and ARBs should not be used in pregnant or sexually active girlspregnant or sexually active girls
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3030
Special Considerations ndash Pregnant Special Considerations ndash Pregnant PatientsPatients
Therapy should minimize risks to mother but should also Therapy should minimize risks to mother but should also not compromise well-being of fetusnot compromise well-being of fetus
Antihypertensives taken before pregnancy (except Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued ACEIs and ARBs) may be continued
Methyldopa and hydralazine are most extensively Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first evaluated so should be the recommended when first diagnoseddiagnosed
BBs compare favourably with methyldopa but use in BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth early pregnancy may be associated with growth retardation of fetusretardation of fetus
ACEIs and ARBS cause serious neonatal problemsACEIs and ARBS cause serious neonatal problems
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3131
Special Considerations ndash Special Considerations ndash Cerebrovascular DiseaseCerebrovascular Disease
Antihypertensive medications are indicated in Antihypertensive medications are indicated in CVAs however it is appropriate to withhold CVAs however it is appropriate to withhold treatment immediately after an event unless BP treatment immediately after an event unless BP is very highis very high
Control BP at 160110 mm Hg until condition Control BP at 160110 mm Hg until condition stabilizes stabilizes
Recurrent stroke are lowered by combination of Recurrent stroke are lowered by combination of an ACEI and thiazide diuretican ACEI and thiazide diuretic
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3232
Special Considerations ndash CAD Special Considerations ndash CAD PatientsPatients
These patients are at high risk for CV morbidity and These patients are at high risk for CV morbidity and mortalitymortality
Avoid rapid lowering of BP esp when reflex tachycardia Avoid rapid lowering of BP esp when reflex tachycardia and sympathetic stimulation occursand sympathetic stimulation occurs
CCBs and BBs are useful where angina is present with CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBsHTN but avoid short-acting CCBs
After MI ACEIs BBs and aldosterone antagonists have After MI ACEIs BBs and aldosterone antagonists have proven to be most beneficialproven to be most beneficial
ACEIs are useful after an MI esp in LV dysfunction ACEIs are useful after an MI esp in LV dysfunction Intensive lipid management and ASA therapy are also Intensive lipid management and ASA therapy are also
indicatedindicated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3333
Special Considerations ndash CHF Special Considerations ndash CHF PatientsPatients
Control of elevated BP improves Control of elevated BP improves myocardial function and prevents or myocardial function and prevents or reduces heart failurereduces heart failure
ACEIs administered after an MI prevents ACEIs administered after an MI prevents subsequent heart failure and reduces subsequent heart failure and reduces morbidity and mortalitymorbidity and mortality
In CHF alone ACEIs used alone or in In CHF alone ACEIs used alone or in combination with digoxin or diuretics combination with digoxin or diuretics reduce morbidity and mortalityreduce morbidity and mortality
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3434
Special Considerations ndash CHF Special Considerations ndash CHF Patients contPatients cont
ACEIs BBs ARBs and aldosterone ACEIs BBs ARBs and aldosterone inhibitors are recommended along with inhibitors are recommended along with diureticsdiuretics
Dihydropyridine CCBs eg amlodipine and Dihydropyridine CCBs eg amlodipine and felodipine have been demonstrated to be felodipine have been demonstrated to be safe in patients with angina HTN and LV safe in patients with angina HTN and LV dysfunctiondysfunction
Hydralazine and ISDN can be used when Hydralazine and ISDN can be used when ACEIs are not toleratedACEIs are not tolerated
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3535
Special Considerations ndash LV Special Considerations ndash LV HypertrophyHypertrophy
LVH is a major risk factor for sudden LVH is a major risk factor for sudden cardiac death MI stroke and other CV cardiac death MI stroke and other CV eventsevents
All antihypertensive agents (except direct All antihypertensive agents (except direct vasodilators) weight reduction and salt vasodilators) weight reduction and salt reduction reduce LV mass and wall reduction reduce LV mass and wall thicknessthickness
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3636
Special Considerations ndash Special Considerations ndash Peripheral Arterial DiseasePeripheral Arterial Disease
Data not available to determine if anti-Data not available to determine if anti-hypertensive treatment alters the course hypertensive treatment alters the course of the diseaseof the disease
Any class of drug may be usedAny class of drug may be used
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3737
Special Considerations ndash DM Special Considerations ndash DM PatientsPatients
Antihypertensive therapy should be initiated Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal with lifestyle modification to achieve target goal of 13080 mm Hgof 13080 mm Hg
Thiazide diuretics ACEIs alpha blockers CCBs Thiazide diuretics ACEIs alpha blockers CCBs and ARBs are beneficial in reducing CVD and and ARBs are beneficial in reducing CVD and strokes in DM patientsstrokes in DM patients
ACEIs and ARBs are preferred in patients with ACEIs and ARBs are preferred in patients with diabetic nephropathydiabetic nephropathy
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3838
Special Considerations ndash COPD or Special Considerations ndash COPD or Asthma PatientsAsthma Patients
BBs and alpha-beta blockers may BBs and alpha-beta blockers may exacerbate asthmaexacerbate asthma
If asthma patient on ACEIs develop a If asthma patient on ACEIs develop a cough treat with ARBscough treat with ARBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 3939
Special Considerations ndash Patients Special Considerations ndash Patients with Hyperlipidemiawith Hyperlipidemia
Lifestyle modifications should be employedLifestyle modifications should be employed In high doses thiazides and loop diuretics may In high doses thiazides and loop diuretics may
produce increases in total cholesterol TGs and produce increases in total cholesterol TGs and LDL cholesterolLDL cholesterol
BBs may increase TGs transiently and increase BBs may increase TGs transiently and increase HDLHDL
ACEIs ARBs CCBs and alpha agonists have ACEIs ARBs CCBs and alpha agonists have clinically neutral effects on lipids and clinically neutral effects on lipids and lipoproteinslipoproteins
Aggressive treatment with statins provide Aggressive treatment with statins provide protection against CHDprotection against CHD
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4040
Special Considerations - GoutSpecial Considerations - Gout All diuretics can increase serum uric acid All diuretics can increase serum uric acid
levels rarely cause goutlevels rarely cause gout Diuretic-induced hyper-uricemia does not Diuretic-induced hyper-uricemia does not
require treatment in the absence of goutrequire treatment in the absence of gout
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4141
Special Considerations ndash Special Considerations ndash Patients with Renal DiseasePatients with Renal Disease
Aggressive management is desired to achieve Aggressive management is desired to achieve target BP goal of 13080target BP goal of 13080
Three or more drugs may be required to reach Three or more drugs may be required to reach target BPtarget BP
ACEIs and ARBs heve favorable effects on ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal progression of diabetic and non-diabetic renal diseasedisease
Loop diuretics are usually required along with Loop diuretics are usually required along with other drugs when GFR lt 30 mlminother drugs when GFR lt 30 mlmin
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4242
Hypertensive Urgencies amp Hypertensive Urgencies amp EmergenciesEmergencies
Associated with marked BP elevations (greater Associated with marked BP elevations (greater that 200120 andor evidence of optic disc that 200120 andor evidence of optic disc edema and target organ complicationsedema and target organ complications
Urgencies ndash situations where BP is marked Urgencies ndash situations where BP is marked elevated but without acute target organ damage elevated but without acute target organ damage and reduction should take place within a few and reduction should take place within a few hourshours
Can be managed with oral doses of drugs which Can be managed with oral doses of drugs which have fast onset of actionhave fast onset of action
Examples include loop diuretics BBs ACEIs Examples include loop diuretics BBs ACEIs alpha agonists or CCBsalpha agonists or CCBs
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4343
Hypertensive EmergenciesHypertensive Emergencies Require immediate blood pressure reduction to prevent or limit Require immediate blood pressure reduction to prevent or limit
target organ damagetarget organ damage
Examples include hypertensive encephalopathy intracranial Examples include hypertensive encephalopathy intracranial hemorrhage unstable angina pectoris AMI aortic aneurysm and hemorrhage unstable angina pectoris AMI aortic aneurysm and eclampsiaeclampsia
Initial treatment is usually with parenteral drugs eg Nitroprusside Initial treatment is usually with parenteral drugs eg Nitroprusside hydralazine enalaprilathydralazine enalaprilat
Goal is to reduce BP by 25 within minutes to 2 hours then Goal is to reduce BP by 25 within minutes to 2 hours then towards 160100 within 2 to six hourstowards 160100 within 2 to six hours
Use of sublingual nifedipine though widely practised is associated Use of sublingual nifedipine though widely practised is associated with serious side effects and is unacceptablewith serious side effects and is unacceptable
BP should be monitored at 15 to 30 minute intervalsBP should be monitored at 15 to 30 minute intervals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4444
Resistant HypertensionResistant Hypertension
Failure to achieve target BP goal despite Failure to achieve target BP goal despite adherence to appropriate therapyadherence to appropriate therapy
Should explore reasons for failure (drug-Should explore reasons for failure (drug-induced causes primary aldosteronism induced causes primary aldosteronism renovascular disease CRF chronic steroid renovascular disease CRF chronic steroid therapytherapy
Consultation with hypertensive specialist should Consultation with hypertensive specialist should be consideredbe considered
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4545
Medications used in HypertensionMedications used in Hypertension
Diuretics ndash mainstay of therapy in most Diuretics ndash mainstay of therapy in most trialstrials
3 types ndash thiazides loop and potassium ndash3 types ndash thiazides loop and potassium ndashsparingsparing
Thiazides- effective in small doses (eg Thiazides- effective in small doses (eg HCTZ125 to 25 mg)HCTZ125 to 25 mg)
All thiazide diuretics are equally effective All thiazide diuretics are equally effective in lowering BPin lowering BP
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4646
Loop DiureticsLoop Diuretics
Bumetanide 05 ndash 4 mg qd or bidBumetanide 05 ndash 4 mg qd or bid
FurosemideFurosemide 40 ndash 240mg qd or bid40 ndash 240mg qd or bid
TorsemideTorsemide 5 ndash 100mg qd or bid 5 ndash 100mg qd or bid
Ethacrynic acid 25 ndash 100mg bid or tidEthacrynic acid 25 ndash 100mg bid or tid
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4747
Potassium-sparing DiureticsPotassium-sparing Diuretics
Amiloride ndashAmiloride ndashmay be used in combination productsmay be used in combination products
Eplerenone ndash Eplerenone ndash shown very good efficacy particularly shown very good efficacy particularly in blacksin blacks
Spironolactone ndash Spironolactone ndash rarely used as antihypertensiverarely used as antihypertensive
Triamterene - Triamterene - may be used in combination productsmay be used in combination products
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4848
Alpha-1 receptor blockersAlpha-1 receptor blockers
DoxazosinDoxazosin PrazosinPrazosin TerazosinTerazosin A beneficial effect of selective A beneficial effect of selective αα11-receptor -receptor
is that they provide symptomatic benefit to is that they provide symptomatic benefit to patients with benign prostatic hypertrophypatients with benign prostatic hypertrophy
A potentially severe side effect is the first A potentially severe side effect is the first dose phenomenondose phenomenon
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 4949
Alpha agonistsAlpha agonists
ClonidineClonidine MethyldopaMethyldopa Chronic use results in sodium and water Chronic use results in sodium and water
retention especially with methyldoparetention especially with methyldopa Sedation and dry mouth are common side Sedation and dry mouth are common side
effectseffects These agents may cause depression These agents may cause depression
orthostatic hypotension and dizziness and orthostatic hypotension and dizziness and rebound hypertensionrebound hypertension
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5050
Beta BlockersBeta Blockers
MOAMOA reduce BP by reducing cardiac reduce BP by reducing cardiac output output
Propranolol is the prototypePropranolol is the prototype Pindolol and acebutalol have ISAPindolol and acebutalol have ISA Carvedilol has Carvedilol has α and β blocking propertiesα and β blocking properties Atenolol and nadolol have long half-life and are Atenolol and nadolol have long half-life and are
excreted renallyexcreted renally Adv EffectsAdv Effects bradycardia bronchospasm bradycardia bronchospasm
AV conduction abnormalitiesAV conduction abnormalities
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5151
ACE InhibitorsACE Inhibitors
Captopril enalapril lisinopril Fosinopril Captopril enalapril lisinopril Fosinopril Quinapril Prinivil Ramipril BenazeprilQuinapril Prinivil Ramipril Benazepril
MOA block production of angiotensin II a MOA block production of angiotensin II a potent vasoconstrictorpotent vasoconstrictor
Captopril absorption is decreased 30 ndash 40 by Captopril absorption is decreased 30 ndash 40 by foodfood
Adv Effects cough dysgeusia hyperkalemia Adv Effects cough dysgeusia hyperkalemia skin rash angioedema proteinuriaskin rash angioedema proteinuria
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5252
Calcium Channel BlockersCalcium Channel Blockers
Verapamil Diltiazem Nifedipine Isradipine Verapamil Diltiazem Nifedipine Isradipine Nicardipine Felodipine AmlodipineNicardipine Felodipine Amlodipine
MOAMOA inhibit influx of extracellular calcium inhibit influx of extracellular calcium into smooth muscle cells and cause smooth into smooth muscle cells and cause smooth muscle relaxation and vasodilationmuscle relaxation and vasodilation
Nifedipine cause greatest peripheral Nifedipine cause greatest peripheral vasodilation cause reflex tachycardiavasodilation cause reflex tachycardia
Verapamil slows HR and AV conduction Verapamil slows HR and AV conduction diltiazem to a lesser extentdiltiazem to a lesser extent
Other AdvEffects dizziness flushing HA Other AdvEffects dizziness flushing HA (Nif) constipation is common with verapamil(Nif) constipation is common with verapamil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5353
Angiotensin II-Receptor Angiotensin II-Receptor AntagonistsAntagonists
Losartan valsartan irbesartan Losartan valsartan irbesartan candesartan telmisartancandesartan telmisartan
MOAMOA Block the effects of angiotensin II Block the effects of angiotensin II at the receptor siteat the receptor site
ARBs are well tolerated and are as ARBs are well tolerated and are as effective as ACEIs in decreasing BPeffective as ACEIs in decreasing BP
Adv Effects dizziness HA GI Adv Effects dizziness HA GI disturbancesdisturbances
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5454
VasodilatorsVasodilators
Hydralazine MinoxidilHydralazine Minoxidil Cause direct arteriolar smooth muscle Cause direct arteriolar smooth muscle
relaxation and vasodilationrelaxation and vasodilation Direct vasodilation can precipitate angina in Direct vasodilation can precipitate angina in
patients with CAD therefore use BBspatients with CAD therefore use BBs Use with BB and diureticUse with BB and diuretic AdvEffects SLE-like syndrome HA dermatitis AdvEffects SLE-like syndrome HA dermatitis
peripheral neuropathy (hydralazine) peripheral neuropathy (hydralazine) hypertrichosis from minoxidilhypertrichosis from minoxidil
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5555
Postganglionic Sympathetic Postganglionic Sympathetic Inhibitors Inhibitors
Guanethidine guanadrelGuanethidine guanadrel MOA deplete NE from PGS nerve MOA deplete NE from PGS nerve
terminals and inhibit NE release leading to terminals and inhibit NE release leading to decreased CO and TPRdecreased CO and TPR
Adv Effects postural hypotension Adv Effects postural hypotension impotence weight gain GI complaintsimpotence weight gain GI complaints
Restricted to use in refractory HTNRestricted to use in refractory HTN
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5656
RESERPINERESERPINE
MOA depletes NE from sympathetic nerve MOA depletes NE from sympathetic nerve endings and blocks transport into storage endings and blocks transport into storage granulesgranules
Takes 2- 6 weeks for maximal effectTakes 2- 6 weeks for maximal effect Causes significant Na and water retentionCauses significant Na and water retention Unopposed parasympathetic activity results in Unopposed parasympathetic activity results in
nasal stuffiness GI effects and bradycardianasal stuffiness GI effects and bradycardia Other Adv EffectsOther Adv Effects depression impotencedepression impotence
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5757
Imidazoline receptor binding drugsImidazoline receptor binding drugs
Example is Relminidine (HyperiumExample is Relminidine (HyperiumRR)) II11imidazoline selective agonist imidazoline selective agonist acts by reducing sympathetic overactivity and acts by reducing sympathetic overactivity and
inhibits renal sodium absorptioninhibits renal sodium absorption Selectivity for ISelectivity for I11 receptors over alpha receptors over alpha11 receptors receptors
provides the advantage of less central side provides the advantage of less central side effects (drowsiness dry mouth)effects (drowsiness dry mouth)
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5858
COMBINATION PRODUCTSCOMBINATION PRODUCTS
ACEIs and CCBs ACEIs and CCBs eg amlodipine and benazepril (Lotrel)eg amlodipine and benazepril (Lotrel)
ACEIs and Diuretics ACEIs and Diuretics eg enalapril + HCTZ ( Vaseretic)eg enalapril + HCTZ ( Vaseretic)
ARBs and DiureticsARBs and Diuretics egLosartan + HCTZ (Hyzaar) egLosartan + HCTZ (Hyzaar)
BBs and Diuretics BBs and Diuretics egAtenolol + Chlorthalidone (Tenoretic)egAtenolol + Chlorthalidone (Tenoretic)
Centrally acting drugs and Diuretics Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril)(methyldopa + HCTZ (Aldoril)
Diuretic and Diuretic Diuretic and Diuretic eg amiloride + HCTZ (Moduretic)eg amiloride + HCTZ (Moduretic)
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
New and Emerging Treatments New and Emerging Treatments for Hypertensionfor Hypertension
Aliskiren ‐ a direct renin inhibitorAliskiren ‐ a direct renin inhibitor Effective and safe but better than existing Effective and safe but better than existing
methods of RAAS inhibitionmethods of RAAS inhibition Outcome studies neededOutcome studies needed
Nebivolol ‐ a 3rd generation szlig‐blockerNebivolol ‐ a 3rd generation szlig‐blocker Effective and safe but better than other szlig‐Effective and safe but better than other szlig‐
blockersblockers Initial outcome study was positive but Initial outcome study was positive but
more aremore are needed in patients with compelling needed in patients with compelling
indicationsindications
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 5959
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
AliskirenAliskiren A highly specific direct renin inhibitor that reduces A highly specific direct renin inhibitor that reduces
plasma renin activity (PRA) by 80 despite plasma renin activity (PRA) by 80 despite compensatory increases in plasma renin compensatory increases in plasma renin concentrations (PRC)concentrations (PRC)
Poor oral bioavailability (asymp 25) and food reduces Poor oral bioavailability (asymp 25) and food reduces AUC by 70 or moreAUC by 70 or more
Half‐life = 24 to 36 hoursHalf‐life = 24 to 36 hours Metabolized by CYP 3A4 and 25 is excreted Metabolized by CYP 3A4 and 25 is excreted
unchanged in urineunchanged in urine No dosing adjustments needed based on age No dosing adjustments needed based on age
hepatic or renal insufficiencyhepatic or renal insufficiencyGradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP Gradman AH J Am Coll Cardiol 2008 51 519‐28 Daughtery KK AJHP
2008651323-322008651323-32E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6060
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
What is NebivololWhat is Nebivolol
Brand name BystolicregBrand name Bystolicreg ldquoldquo3rd generationrdquo highly selective szlig1‐blocker with 3rd generationrdquo highly selective szlig1‐blocker with
vasodilation induced by release of nitrous oxidevasodilation induced by release of nitrous oxide Does NOT have alpha blocking OR intrinsic Does NOT have alpha blocking OR intrinsic
sympathomimetic activity (ISA)sympathomimetic activity (ISA) Racemic mixtureRacemic mixture
l‐isomer szlig‐blocking activityl‐isomer szlig‐blocking activity d‐isomer nitrous oxide released‐isomer nitrous oxide release
1048698 1048698 Extensive first pass metabolismExtensive first pass metabolism
Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33Veverka A Ann Pharmacother 2006401353‐60 Gray C AJHP 2008 65 1125‐33
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6161
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
E Brown-Myrie Pharm DE Brown-Myrie Pharm D 6262
Summary of JNC V11 ReportSummary of JNC V11 Report
Normal BP is lt 12080Normal BP is lt 12080 Prehypertension is 120-13980-89Prehypertension is 120-13980-89 Stage I is similar to JNC VI ReportStage I is similar to JNC VI Report Stage 2 incorporates stages 2 and 3 of Sixth Stage 2 incorporates stages 2 and 3 of Sixth
ReportReport Treatment should consider presence or Treatment should consider presence or
absence of compelling indicationsabsence of compelling indications Encourage healthy lifestyle for all individualsEncourage healthy lifestyle for all individuals
