Chapter 15: Cardiovascular Drugs Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All...

Chapter 15:Chapter 15:

Cardiovascular DrugsCardiovascular Drugs

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

22Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 15 OutlineChapter 15 Outline

Cardiovascular DrugsCardiovascular Drugs Dental implications of cardiovascular diseaseDental implications of cardiovascular disease Cardiac glycosidesCardiac glycosides Antiarrhythmic agentsAntiarrhythmic agents Antianginal drugsAntianginal drugs Antihypertensive agentsAntihypertensive agents Antihyperlipidemic agentsAntihyperlipidemic agents Drugs that affect blood coagulationDrugs that affect blood coagulation


Cardiovascular DrugsCardiovascular Drugs

Haveles (p. 186)Haveles (p. 186) Cardiovascular diseaseCardiovascular disease refers to diseases of refers to diseases of

the heart and blood vesselsthe heart and blood vessels Includes hypertension, angina pectoris, Includes hypertension, angina pectoris,

coronary artery disease, cerebrovascular coronary artery disease, cerebrovascular accident, and congestive heart failure (CHF)accident, and congestive heart failure (CHF)

A leading cause of death in the United StatesA leading cause of death in the United States 25% of the top 200 drugs are in this group25% of the top 200 drugs are in this group


Dental Implications of Dental Implications of Cardiovascular DiseaseCardiovascular Disease

Haveles (p. 187) Haveles (p. 187) Contraindications to treatmentContraindications to treatment Vasoconstrictor limitVasoconstrictor limit Infective endocarditisInfective endocarditis Cardiac pacemakersCardiac pacemakers Periodontal disease and cardiovascular diseasePeriodontal disease and cardiovascular disease


Contraindications to TreatmentContraindications to Treatment

Haveles (p. 187) (Box 15-1)Haveles (p. 187) (Box 15-1) Acute or recent myocardial infarction (MI) Acute or recent myocardial infarction (MI)

(within the preceding 3 to 6 months)(within the preceding 3 to 6 months) Unstable or recent onset of angina pectorisUnstable or recent onset of angina pectoris Uncontrolled CHFUncontrolled CHF Uncontrolled arrhythmiasUncontrolled arrhythmias Significant, uncontrolled hypertensionSignificant, uncontrolled hypertension


Vasoconstrictor LimitVasoconstrictor Limit

Haveles (p. 187)Haveles (p. 187) The majority of cardiovascular patients should The majority of cardiovascular patients should

benefit from the use of epinephrine in the local benefit from the use of epinephrine in the local anesthetic agentanesthetic agent The amount and effect of epinephrine administered The amount and effect of epinephrine administered

must be weighed against the fact that discomfort must be weighed against the fact that discomfort can cause the release of endogenous epinephrinecan cause the release of endogenous epinephrine

Limiting the dose to the cardiac dose (0.04 mg) may Limiting the dose to the cardiac dose (0.04 mg) may be warranted in a few severely affected patientsbe warranted in a few severely affected patients


Infective EndocarditisInfective Endocarditis

Haveles (p. 187)Haveles (p. 187) When a risk of producing infective endocarditis When a risk of producing infective endocarditis

exists, prophylactic antibiotics should be exists, prophylactic antibiotics should be prescribed, if warranted by the dental prescribed, if warranted by the dental procedure being performedprocedure being performed


Cardiac PacemakersCardiac Pacemakers

Haveles (p. 187)Haveles (p. 187) A cardiac pacemaker is an electrical device A cardiac pacemaker is an electrical device

implanted in a patient’s chest to regulate the implanted in a patient’s chest to regulate the heart rhythmheart rhythm If not appropriately shielded, some electrical devices If not appropriately shielded, some electrical devices

used in dentistry may interfere with pacemaker used in dentistry may interfere with pacemaker activityactivity

Consult with physician may be appropriate before Consult with physician may be appropriate before treatmenttreatment


Periodontal Disease and Periodontal Disease and Cardiovascular DiseaseCardiovascular Disease

Haveles (p. 187)Haveles (p. 187) Research has found a relationship between Research has found a relationship between

periodontal disease and both cardiovascular periodontal disease and both cardiovascular disease and strokedisease and stroke An inherited phenotype, An inherited phenotype, MO,MO, is under both genetic is under both genetic

and environmental influences, placing the patient and environmental influences, placing the patient at increased risk for severe periodontal disease, at increased risk for severe periodontal disease, insulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, atherosclerosis, and emboli productionatherosclerosis, and emboli production

cont’d…cont’d…


Periodontal Disease and Periodontal Disease and Cardiovascular DiseaseCardiovascular Disease

Monocytes in these patients secrete Monocytes in these patients secrete abnormally high levels of cytokines, including abnormally high levels of cytokines, including prostaglandin (PG)Eprostaglandin (PG)E22, interleukin (IL)-1, interleukin (IL)-1ββ, and , and

tumor necrosis factor (TNF)-tumor necrosis factor (TNF)-αα, all of which , all of which are associated with both periodontal and are associated with both periodontal and cardiovascular diseasecardiovascular disease

An increase in dietary intake of fat leads to an An increase in dietary intake of fat leads to an increase in low-density lipoproteins (LDL, bad increase in low-density lipoproteins (LDL, bad cholesterol), which are known to upregulate cholesterol), which are known to upregulate the destructive monocyte responsethe destructive monocyte response


Cardiac GlycosidesCardiac Glycosides

Haveles (pp. 187-189)Haveles (pp. 187-189) CHFCHF Digitalis glycosidesDigitalis glycosides


Heart Failure Heart Failure

Haveles (pp. 187-188) (Fig. 15-1)Haveles (pp. 187-188) (Fig. 15-1) In CHF, the heart does not provide adequate In CHF, the heart does not provide adequate

cardiac output cardiac output Blood accumulates in the failing ventricle(s), the Blood accumulates in the failing ventricle(s), the

ventricle(s) enlarges and finally becomes ventricle(s) enlarges and finally becomes ineffective as a pumpineffective as a pump• Left side failure backs into pulmonary circulation (lungs) Left side failure backs into pulmonary circulation (lungs)

leading to edema, leading to edema, dyspneadyspnea and and orthopneaorthopnea

• Right side failure causes systemic congestion, leading to Right side failure causes systemic congestion, leading to peripheral edema with fluid accumulation evidenced by peripheral edema with fluid accumulation evidenced by pitting edema (pitting edema (pedal pedal edema)edema)


Digitalis GlycosidesDigitalis Glycosides

Haveles (pp. 188-189)Haveles (pp. 188-189) Pharmacologic effectsPharmacologic effects UsesUses Adverse reactionsAdverse reactions Management of the dental patient taking Management of the dental patient taking

digoxindigoxin Other drugsOther drugs



Digitalis GlycosidesDigitalis Glycosides

Haveles (p. 188)Haveles (p. 188) The most common type of drug used in the The most common type of drug used in the

treatment of CHFtreatment of CHF Not considered first-line therapyNot considered first-line therapy

digoxin (Lanoxin) is used as the prototypedigoxin (Lanoxin) is used as the prototype


Pharmacologic Effects of Digitalis Pharmacologic Effects of Digitalis GlycosidesGlycosides

Haveles (p. 188)Haveles (p. 188) Increases force and strength of contraction of Increases force and strength of contraction of

the myocardium (positive inotropic effect)the myocardium (positive inotropic effect) Allows the heart to do more work without Allows the heart to do more work without

increasing the use of oxygenincreasing the use of oxygen The heart becomes more efficient, and cardiac The heart becomes more efficient, and cardiac

output increasesoutput increases



Pharmacologic Effects of Digitalis Pharmacologic Effects of Digitalis GlycosidesGlycosides

In CHF, the heart rate is increased due to increased In CHF, the heart rate is increased due to increased sympathetic action resulting from decreased carbon sympathetic action resulting from decreased carbon monoxide (CO)monoxide (CO) As digoxin increases CO, sympathetic tone is decreased, As digoxin increases CO, sympathetic tone is decreased,

with a decrease in heart ratewith a decrease in heart rate Digoxin also reduces edema that occurs with CHFDigoxin also reduces edema that occurs with CHF

The size of the heart is reduced as excess blood The size of the heart is reduced as excess blood volume is removed via the kidneysvolume is removed via the kidneys

Digoxin can affect automaticity, conduction velocity, Digoxin can affect automaticity, conduction velocity, and refractory periods of different parts of the heart and refractory periods of different parts of the heart in different waysin different ways


Uses of Digitalis GlycosidesUses of Digitalis Glycosides

Haveles (p. 188)Haveles (p. 188) Most common usage is treatment of CHFMost common usage is treatment of CHF

Also used for atrial arrhythmias, including atrial Also used for atrial arrhythmias, including atrial fibrillation (AF) and paroxysmal atrial tachycardia fibrillation (AF) and paroxysmal atrial tachycardia (PAT)(PAT)

A recent trial found digoxin did not reduce A recent trial found digoxin did not reduce mortality; for this reason use of digoxin is mortality; for this reason use of digoxin is decreasingdecreasing Angiotensin-converting enzyme inhibitors (ACEIs), Angiotensin-converting enzyme inhibitors (ACEIs),

angiotensin receptor blockers (ARBs) and angiotensin receptor blockers (ARBs) and ββ--adrenergic blockers are used more oftenadrenergic blockers are used more often


Adverse Reactions of Digitalis Adverse Reactions of Digitalis GlycosidesGlycosides

Haveles (pp. 188-189)Haveles (pp. 188-189) Narrow therapeutic index: slight changes in Narrow therapeutic index: slight changes in

dose, absorption, or metabolism can trigger toxic dose, absorption, or metabolism can trigger toxic symptomssymptoms

Gastrointestinal (GI): signs of toxicity include Gastrointestinal (GI): signs of toxicity include anorexia,anorexia, nausea, vomiting, copious salivation nausea, vomiting, copious salivation

Arrhythmias: if sufficient overdose is given (note: Arrhythmias: if sufficient overdose is given (note: digitalis is used to treat arrhythmias, its toxicity digitalis is used to treat arrhythmias, its toxicity can cause them)can cause them)

Neurologic: signs of toxicity include headache, Neurologic: signs of toxicity include headache, drowsiness, and visual disturbancesdrowsiness, and visual disturbances



Adverse Reactions of Digitalis Adverse Reactions of Digitalis GlycosidesGlycosides

Oral: increased salivation is associated with Oral: increased salivation is associated with digoxin toxicitydigoxin toxicity

Dental drug interactions: interaction with Dental drug interactions: interaction with sympathomimetics can increase chances of sympathomimetics can increase chances of arrhythmias; in severe cardiac disease, the arrhythmias; in severe cardiac disease, the epinephrine dose may be limited to the epinephrine dose may be limited to the cardiac dose (0.04 mg) cardiac dose (0.04 mg) Erythromycin and tetracycline can increase toxicity Erythromycin and tetracycline can increase toxicity

of digoxin in some patientsof digoxin in some patients


Management of the Dental Management of the Dental Patient Taking Digoxin Patient Taking Digoxin

Haveles (p. 189) (Box 15-2)Haveles (p. 189) (Box 15-2) Watch for overdose side effects such as Watch for overdose side effects such as

nausea, vision changes, and copious salivationnausea, vision changes, and copious salivation Use epinephrine with caution to minimize Use epinephrine with caution to minimize

arrhythmiasarrhythmias Monitor pulse to check for bradycardiaMonitor pulse to check for bradycardia Tetracycline and erythromycin can increase Tetracycline and erythromycin can increase

digoxin levels (in digoxin levels (in approximatelyapproximately 10% of 10% of patients)patients)


Other Drugs Other Drugs

Haveles (p. 189) (Note: these are not cardiac Haveles (p. 189) (Note: these are not cardiac glycosides)glycosides)

ACEIs: now first-line therapy for CHFACEIs: now first-line therapy for CHF ARBs: for patients who cannot tolerate ACEIs; ARBs: for patients who cannot tolerate ACEIs;

also first-line therapyalso first-line therapy ββ-Adrenergic blockers-Adrenergic blockers Vasodilators: hydralazine and isosorbide Vasodilators: hydralazine and isosorbide

dinitratedinitrate Diuretics: to relieve edemaDiuretics: to relieve edema Aldosterone antagonistsAldosterone antagonists


Antiarrhythmic AgentsAntiarrhythmic Agents

Haveles (pp. 189-191)Haveles (pp. 189-191) AutomaticityAutomaticity Action potentialAction potential ArrhythmiasArrhythmias Antiarrhythmic agentsAntiarrhythmic agents Adverse reactionsAdverse reactions Dental implicationsDental implications




Haveles (p. 189) Haveles (p. 189) Arrhythmias may result from abnormal Arrhythmias may result from abnormal

impulse generation or abnormal impulse impulse generation or abnormal impulse conductionconduction Cardiac diseases such as myocardial anorexia, Cardiac diseases such as myocardial anorexia,

arteriosclerosis, and heart block can produce arteriosclerosis, and heart block can produce arrhythmiasarrhythmias

Antiarrhythmic agents are used to prevent Antiarrhythmic agents are used to prevent arrhythmiasarrhythmias


Automaticity Automaticity

Haveles (pp. 189-190) (Fig. 15-2)Haveles (pp. 189-190) (Fig. 15-2) Cells of cardiac muscles have an intrinsic Cells of cardiac muscles have an intrinsic

rhythm called rhythm called automaticityautomaticity The sinoatrial (SA) node in right atrium has the The sinoatrial (SA) node in right atrium has the

fastest rate of depolarization and directs other cells fastest rate of depolarization and directs other cells of the heartof the heart• It is innervated by both the parasympathetic and It is innervated by both the parasympathetic and

sympathetic nervous systemsympathetic nervous system

It signals the atrioventricular (AV) node, which It signals the atrioventricular (AV) node, which sends signals through the bundle of His to Purkinje sends signals through the bundle of His to Purkinje fibers and ventriclesfibers and ventricles


Action PotentialAction Potential

Haveles (p. 190) (Fig. 15-2)Haveles (p. 190) (Fig. 15-2) Electrical excitation from the nerve produces Electrical excitation from the nerve produces

movement of ions across the membrane, movement of ions across the membrane, generating an action potentialgenerating an action potential Visualized as an electrocardiogram (ECG)Visualized as an electrocardiogram (ECG)

A relationship exists between the action A relationship exists between the action potential and the ECG tracing potential and the ECG tracing


ArrhythmiasArrhythmias

Haveles (p. 190)Haveles (p. 190) Arrhythmias are divided into supraventricular Arrhythmias are divided into supraventricular

(atrial) and ventricular types(atrial) and ventricular types May result in tachycardia or bradycardia of May result in tachycardia or bradycardia of

supraventricular or ventricular parts of the heartsupraventricular or ventricular parts of the heart May result from ectopic foci “emergent May result from ectopic foci “emergent

leaders” that preempt the SA or AV nodal rateleaders” that preempt the SA or AV nodal rate



Haveles (pp. 190-191) (Tables 15-1, 15-2)Haveles (pp. 190-191) (Tables 15-1, 15-2) Placed in four groups designated by numeral Placed in four groups designated by numeral

I through IV according to mechanism of I through IV according to mechanism of actionaction Subsets of these Roman numerals use capital Subsets of these Roman numerals use capital

letters (A, B, C)letters (A, B, C)




Antiarrhythmic agents work by depressing Antiarrhythmic agents work by depressing parts of the heart that are beating abnormallyparts of the heart that are beating abnormally They may decrease the velocity of depolarization, They may decrease the velocity of depolarization,

decrease impulse propagation, and inhibit decrease impulse propagation, and inhibit aberrant impulse propagationaberrant impulse propagation




Haveles (p. 191)Haveles (p. 191) Digoxin: although digoxin is not included in Digoxin: although digoxin is not included in

the other groups of antiarrhythmics, it is used the other groups of antiarrhythmics, it is used to treat some arrhythmiasto treat some arrhythmias Shortens the refractory period of atrial and Shortens the refractory period of atrial and

ventricular tissues while prolonging the refractory ventricular tissues while prolonging the refractory period and diminishing the conduction velocity in period and diminishing the conduction velocity in the Purkinje fibersthe Purkinje fibers


Adverse Reactions of Adverse Reactions of Antiarrhythmic AgentsAntiarrhythmic Agents

Haveles (p. 191)Haveles (p. 191) Antiarrhythmic agents have a narrow Antiarrhythmic agents have a narrow

therapeutic index and are difficult to managetherapeutic index and are difficult to manage Only used for patients with arrhythmias that Only used for patients with arrhythmias that

prevent the proper functioning of the heartprevent the proper functioning of the heart


Classification and Mechanism of Classification and Mechanism of Action of the Antiarrhythmic AgentsAction of the Antiarrhythmic Agents

Haveles (p. 191) (Table 15-1)Haveles (p. 191) (Table 15-1) Class IA sodium (NaClass IA sodium (Na++) channel blocker ) channel blocker

(medium)(medium) Quinidine, procainamide, disopyramideQuinidine, procainamide, disopyramide

Class IB NaClass IB Na+ + channel blocker (fast)channel blocker (fast) lidocaine lidocaine

Class IC NaClass IC Na+ + channel blocker (slow)channel blocker (slow) Flecainide, encainide, propafenoneFlecainide, encainide, propafenone



Classification and Mechanism of Classification and Mechanism of Action of Antiarrhythmic AgentsAction of Antiarrhythmic Agents

Class II Class II ββ-blockers-blockers Propranolol, esmolol, acebutolol, sotalolPropranolol, esmolol, acebutolol, sotalol

Class III potassium (KClass III potassium (K++)) channel blockers channel blockers Bretylium and Bretylium and dd-sotalol (non–-sotalol (non–ββ-blocking -blocking

enantiomer)enantiomer) Class IV calcium channel blockers (CCBs)Class IV calcium channel blockers (CCBs)

Verapamil, diltiazem Verapamil, diltiazem


Management of Dental Patients Management of Dental Patients Taking Antiarrhythmic AgentsTaking Antiarrhythmic Agents

Haveles (p. 191) (Table 15-2)Haveles (p. 191) (Table 15-2) All: Check for abnormal or extra beats when taking blood All: Check for abnormal or extra beats when taking blood

pressure and pulsepressure and pulse AF: pt. on warfarin-check international normalized ratio (INR)AF: pt. on warfarin-check international normalized ratio (INR) Amiodarone: liver toxicity, blue skin, photosensitivityAmiodarone: liver toxicity, blue skin, photosensitivity CCBs: gingival enlargementCCBs: gingival enlargement Disopyramide: anticholinergic xerostomiaDisopyramide: anticholinergic xerostomia Procainamide: reversible lupus-like syndrome, 25%-30%, Procainamide: reversible lupus-like syndrome, 25%-30%,

central nervous system (CNS) depression xerostomiacentral nervous system (CNS) depression xerostomia Quinidine: nausea, vomiting, diarrhea; cinchonism with large Quinidine: nausea, vomiting, diarrhea; cinchonism with large

doses; atropine-like effect, xerostomiadoses; atropine-like effect, xerostomia Phenytoin: gingival enlargementPhenytoin: gingival enlargement ββ-Blockers, nonspecific: interaction with epinephrine-Blockers, nonspecific: interaction with epinephrine


Antianginal DrugsAntianginal Drugs

Haveles (pp. 191-194)Haveles (pp. 191-194) Angina pectorisAngina pectoris Nitroglycerin (NTG)-like compoundsNitroglycerin (NTG)-like compounds CCBsCCBs ββ-Adrenergic blocking agents-Adrenergic blocking agents RanolazineRanolazine Dental implicationsDental implications Prevention of an anginal attackPrevention of an anginal attack MIMI


Angina PectorisAngina Pectoris

Haveles (pp. 191-192)Haveles (pp. 191-192) Characterized by pain or discomfort in the Characterized by pain or discomfort in the

chest radiating to the left arm and shoulderchest radiating to the left arm and shoulder Pain can also radiate to neck, back, and lower jawPain can also radiate to neck, back, and lower jaw Jaw pain may be confused with a toothacheJaw pain may be confused with a toothache

Occurs when coronary arteries do not supply Occurs when coronary arteries do not supply enough oxygen to the myocardiumenough oxygen to the myocardium



Angina PectorisAngina Pectoris

Haveles (pp. 191-192) (Table 15-3)Haveles (pp. 191-192) (Table 15-3) At one time, NTG-like compounds were the At one time, NTG-like compounds were the

only drugs that could relieve the symptomsonly drugs that could relieve the symptoms Today, Today, ββ-adrenergic blockers and CCBs have -adrenergic blockers and CCBs have

added a new dimensionadded a new dimension The effect of these drugs is to reduce the The effect of these drugs is to reduce the

workload of the heartworkload of the heart Oxygen requirement of myocardium is reduced, Oxygen requirement of myocardium is reduced,

relieving painful symptomsrelieving painful symptoms


Nitroglycerin-Like CompoundsNitroglycerin-Like Compounds

Haveles (pp. 191-192) (Box 15-3)Haveles (pp. 191-192) (Box 15-3) NTG is by far the most often used nitrate for NTG is by far the most often used nitrate for

management of acute anginal episodesmanagement of acute anginal episodes Also to prevent anginal attacks induced by stress Also to prevent anginal attacks induced by stress

or exerciseor exercise


Mechanism of Nitroglycerin-Like Mechanism of Nitroglycerin-Like CompoundsCompounds

Haveles (p. 192)Haveles (p. 192) NTG is a vasodilator NTG is a vasodilator

Releases free nitrite ion and nitric oxideReleases free nitrite ion and nitric oxide• Nitric oxide activates guanylyl cyclase and increases Nitric oxide activates guanylyl cyclase and increases

cyclic guanosine monophosphate (cGMP), producing cyclic guanosine monophosphate (cGMP), producing relaxation of vascular smooth muscle throughout the relaxation of vascular smooth muscle throughout the bodybody

By reducing workload on the heart, NTG By reducing workload on the heart, NTG decreases the oxygen demanddecreases the oxygen demand



Mechanism of Nitroglycerin-Like Mechanism of Nitroglycerin-Like CompoundsCompounds

Amyl nitrite is a volatile agent in a closed Amyl nitrite is a volatile agent in a closed containercontainer It is administered by crushing the container and It is administered by crushing the container and

inhaling the fumesinhaling the fumes Sublingual (SL) NTG is available as an SL tablet Sublingual (SL) NTG is available as an SL tablet

(Nitrostat) or spray used sublingually (Nitrostat) or spray used sublingually (Nitroingual)(Nitroingual) SL isosorbide dinitrate is also effective for an acute SL isosorbide dinitrate is also effective for an acute

anginal attackanginal attack One of the NTG products should be in the dental One of the NTG products should be in the dental

office emergency kit; the patient should bring office emergency kit; the patient should bring their NTG to each appointmenttheir NTG to each appointment


Adverse Reactions of Adverse Reactions of Nitroglycerin-Like CompoundsNitroglycerin-Like Compounds Haveles (p. 193)Haveles (p. 193)

Most reactions are caused its effect on Most reactions are caused its effect on vascular smooth musclevascular smooth muscle Severe headaches are often reportedSevere headaches are often reported Flushing, hypotension, light-headedness, and Flushing, hypotension, light-headedness, and

syncope can also resultsyncope can also result SL NTG can produce a localized burning or SL NTG can produce a localized burning or

tinglingtingling


Significant Drug Interactions and Significant Drug Interactions and ContraindicationsContraindications

Haveles (p. 193)Haveles (p. 193) Phosphodiesterase 5 (PDE5) inhibitors Phosphodiesterase 5 (PDE5) inhibitors

include sildenafil (Viagra), vardenafil (Levitra), include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)and tadalafil (Cialis) The administration of any of these drugs with The administration of any of these drugs with

doses of any nitrate is contraindicateddoses of any nitrate is contraindicated The combination can cause dangerously low blood The combination can cause dangerously low blood

pressurepressure


Storage of Nitroglycerin-Like Storage of Nitroglycerin-Like CompoundsCompounds

Haveles (p. 193)Haveles (p. 193) NTG is degraded by heat and moisture but not NTG is degraded by heat and moisture but not

by lightby light Tablets should be stored in the original dark-brown Tablets should be stored in the original dark-brown

glass containerglass container• If opened it should be discarded between 3 and 6 months If opened it should be discarded between 3 and 6 months

NTG spray is effective until its expiration dateNTG spray is effective until its expiration date Long-acting NTG-like products are available for Long-acting NTG-like products are available for

long-term prophylaxis of anginal attackslong-term prophylaxis of anginal attacks Dose forms include tablets and topical productsDose forms include tablets and topical products



Storage of Nitroglycerin-Like Storage of Nitroglycerin-Like CompoundsCompounds

With long-term regular use, tolerance developsWith long-term regular use, tolerance develops Prophylactic nitrates should be given with an 8- to Prophylactic nitrates should be given with an 8- to

12- hour “vacation” every day12- hour “vacation” every day The mononitrate dose form requires a 7-hour The mononitrate dose form requires a 7-hour

“vacation” daily“vacation” daily


Examples of Antianginal Examples of Antianginal PreparationsPreparations

Haveles (pp. 192-193) (Table 15-3)Haveles (pp. 192-193) (Table 15-3) Acute attacksAcute attacks

NitritesNitrites• Amyl nitriteAmyl nitrite

Short-acting nitratesShort-acting nitrates• NTG (Nitrostat) (Nitrolingual)NTG (Nitrostat) (Nitrolingual)

• isosorbide dinitrate isosorbide dinitrate



Examples of Antianginal Examples of Antianginal PreparationsPreparations

Prophylactic useProphylactic use Long-acting nitratesLong-acting nitrates

• NTG (Nitro-Bid) (Nitro Dur, Minitran)NTG (Nitro-Bid) (Nitro Dur, Minitran)

• isosorbide dinitrate (Isordil, Sorbitrate-DSC)isosorbide dinitrate (Isordil, Sorbitrate-DSC)

• isosorbide mononitrate (Imdur, Ismo, Monoket)isosorbide mononitrate (Imdur, Ismo, Monoket)

• pentaerythritol tetranitrate (Peritrate)pentaerythritol tetranitrate (Peritrate)

ββ--BlockersBlockers• Propranolol Propranolol

CCBs* (See Box 15-4)CCBs* (See Box 15-4)• verapamil (Calan, Isoptin)verapamil (Calan, Isoptin)• nifedipine (Procardia)nifedipine (Procardia)


Calcium Channel Blocking Calcium Channel Blocking AgentsAgents

Haveles (pp. 193-194) (Table 15-4)Haveles (pp. 193-194) (Table 15-4) Mechanism of action of CCBs for treatment of Mechanism of action of CCBs for treatment of

angina is related to inhibition of movement of angina is related to inhibition of movement of calcium during the contraction of cardiac and calcium during the contraction of cardiac and vascular smooth musclevascular smooth muscle Vasodilation and a decrease in peripheral resistance Vasodilation and a decrease in peripheral resistance

results, decreasing the work of the heartresults, decreasing the work of the heart CCBs are also used in treatment of cardiac CCBs are also used in treatment of cardiac

arrhythmias and hypertensionarrhythmias and hypertension Adverse effects include dizziness, weakness, Adverse effects include dizziness, weakness,

constipation, and hypotensionconstipation, and hypotension Nifedipine is associated with gingival enlargement and Nifedipine is associated with gingival enlargement and

dysgeusiadysgeusia


ββ--Adrenergic Blocking Agents Adrenergic Blocking Agents

Haveles (p. 194)Haveles (p. 194) Used in the treatment of angina (as well as Used in the treatment of angina (as well as

hypertension)hypertension) Block the Block the betabeta response to catecholamine response to catecholamine

stimulation reducing both chronotropic and inotropic stimulation reducing both chronotropic and inotropic effectseffects

Net result is a reduced myocardial oxygen demandNet result is a reduced myocardial oxygen demand Adverse effects include bradycardia, CHF, Adverse effects include bradycardia, CHF,

headache, dry mouth, blurred vision, and headache, dry mouth, blurred vision, and unpleasant dreamsunpleasant dreams


ranolazineranolazine(Ranexa)(Ranexa)

Haveles (p. 194)Haveles (p. 194) A new drug for treatment of chronic anginaA new drug for treatment of chronic angina

Exact mechanism of action is unknownExact mechanism of action is unknown Should only be used in patients that have not Should only be used in patients that have not

responded to long-acting nitrates, CCBs, and responded to long-acting nitrates, CCBs, and ββ--blockersblockers


Dental ImplicationsDental Implications

Haveles (p. 194)Haveles (p. 194) Treatment of an acute anginal attackTreatment of an acute anginal attack Prevention of anginal attackPrevention of anginal attack MIMI


Treatment of an Acute Anginal Treatment of an Acute Anginal AttackAttack

Before administering NTG, the dental team Before administering NTG, the dental team should make sure the patient has not used a should make sure the patient has not used a PDE5 inhibitor within the past 24 hours; if PDE5 inhibitor within the past 24 hours; if such is the case, call 911such is the case, call 911

The patient’s personal NTG tablets or spray The patient’s personal NTG tablets or spray should be availableshould be available Long-acting nitrates and topical products are not Long-acting nitrates and topical products are not

useful for the treatment of an acute anginal attackuseful for the treatment of an acute anginal attackcont’d…cont’d…


Treatment of an Acute Anginal Treatment of an Acute Anginal AttackAttack

For acute emergencies, the office should For acute emergencies, the office should have a supply of SL NTGhave a supply of SL NTG The patient should be seatedThe patient should be seated Three tablets or doses of spray, each 5 minutes Three tablets or doses of spray, each 5 minutes

apart apart • If the anginal attack is not stopped, the patient should be If the anginal attack is not stopped, the patient should be

taken to the emergency roomtaken to the emergency room


Prevention of Anginal AttackPrevention of Anginal Attack

Haveles (p. 194)Haveles (p. 194) Two methods to prevent an acute anginal Two methods to prevent an acute anginal

attack include pretreatment with either an attack include pretreatment with either an anxiolytic agent or SL NTGanxiolytic agent or SL NTG Anxiolytics: an antianxiety agent, or anxiolytic Anxiolytics: an antianxiety agent, or anxiolytic

(benzodiazepine) may be prescribed to allay (benzodiazepine) may be prescribed to allay anxiety and prevent an acute anginal attackanxiety and prevent an acute anginal attack

NTG: premedicating an anxious patient with SL NTG: premedicating an anxious patient with SL NTG can reduce the chance of an attackNTG can reduce the chance of an attack


Myocardial InfarctionMyocardial Infarction

Haveles (p. 194) Haveles (p. 194) An anginal attack not relieved by three doses An anginal attack not relieved by three doses

of SL NTG may be experiencing an MIof SL NTG may be experiencing an MI If the patient who has not been previously If the patient who has not been previously

diagnosed as having angina experiences chest diagnosed as having angina experiences chest pain, he or she should be taken to an emergency pain, he or she should be taken to an emergency room for diagnosisroom for diagnosis

Any patient with an anginal attack not relieved by Any patient with an anginal attack not relieved by NTG should go to the hospital emergency roomNTG should go to the hospital emergency room


Antihypertensive AgentsAntihypertensive Agents Haveles (pp. 194-205)Haveles (pp. 194-205)

Patient evaluationPatient evaluation Treatment of hypertensionTreatment of hypertension Diuretic agentsDiuretic agents ββ--Adrenergic blocking agentsAdrenergic blocking agents CCBsCCBs Angiotensin-related agentsAngiotensin-related agents Renin inhibitorsRenin inhibitors αα11-Adrenergic blocking agents-Adrenergic blocking agents Other antihypertensive agentsOther antihypertensive agents Management of the dental patient taking Management of the dental patient taking

antihypertensive agentsantihypertensive agentscont’d…cont’d…


Antihypertensive AgentsAntihypertensive Agents

Haveles (pp. 194-196) (Box 15-4)Haveles (pp. 194-196) (Box 15-4) Hypertension is the most common Hypertension is the most common

cardiovascular disease (28.6% of Americans)cardiovascular disease (28.6% of Americans) Even blood pressure within the formerly “normal” Even blood pressure within the formerly “normal”

range is associated with an increase in morbidity range is associated with an increase in morbidity and mortalityand mortality

Eventually, elevated blood pressure damages Eventually, elevated blood pressure damages internal organsinternal organs

More likely to have kidney and heart disease and More likely to have kidney and heart disease and cardiovascular problemscardiovascular problems



Antihypertensive Agents Antihypertensive Agents

Haveles (pp. 195, 197) (Table 15-5)Haveles (pp. 195, 197) (Table 15-5) Hypertension is divided into categories based Hypertension is divided into categories based

on the cause or progression of the diseaseon the cause or progression of the disease Essential (idiopathic, primary): from an unknown Essential (idiopathic, primary): from an unknown

cause, 85% to 90% of patientscause, 85% to 90% of patients Secondary: cause can be identified and Secondary: cause can be identified and

associated to a disease process of endocrine or associated to a disease process of endocrine or renal system (10% of patients)renal system (10% of patients)

Malignant: high or rapidly rising blood pressure, Malignant: high or rapidly rising blood pressure, develops in about 5% of patients with primary or develops in about 5% of patients with primary or secondary hypertensionsecondary hypertension


Patient EvaluationPatient Evaluation

Haveles (p. 195)Haveles (p. 195) Three objectivesThree objectives

To assess lifestyle and identify other To assess lifestyle and identify other cardiovascular risk factors or concomitant cardiovascular risk factors or concomitant disorders that may affect prognosis and treatmentdisorders that may affect prognosis and treatment

To reveal identifiable causes of hypertensionTo reveal identifiable causes of hypertension To assess for the presence or absence of target-To assess for the presence or absence of target-

organ damage or cardiovascular diseaseorgan damage or cardiovascular disease


Treatment of HypertensionTreatment of Hypertension Haveles (pp. 195, 197) (Fig. 15-4; Table 15-6)Haveles (pp. 195, 197) (Fig. 15-4; Table 15-6)

A stepped-care approach as blood pressures A stepped-care approach as blood pressures become greater than 140/90 or less than 130/80 mm become greater than 140/90 or less than 130/80 mm Hg in patients with diabetes or chronic kidney Hg in patients with diabetes or chronic kidney disease disease

Lifestyle modification: stage 1 or stage 2 and Lifestyle modification: stage 1 or stage 2 and everyoneeveryone Weight reduction, physical activity, a diet rich in fruits and Weight reduction, physical activity, a diet rich in fruits and

vegetables, reduced contents of saturated and total fats, vegetables, reduced contents of saturated and total fats, sodium restrictionsodium restriction

Initial drug choices: once diagnosed with stage 1 or Initial drug choices: once diagnosed with stage 1 or stage 2 hypertensionstage 2 hypertension Sex, race, presence of diabetes or hyperlipidemia, and Sex, race, presence of diabetes or hyperlipidemia, and

renin activity are taken into considerationrenin activity are taken into considerationcont’d…cont’d…


Treatment of Hypertension Treatment of Hypertension

Haveles (pp. 195, 199) (Box 15-5)Haveles (pp. 195, 199) (Box 15-5) The Big Five antihypertensive groupsThe Big Five antihypertensive groups

DiureticsDiuretics ββ-Blockers-Blockers CCBsCCBs ACEIsACEIs ARBsARBs


Diuretic Agents for Hypertension Diuretic Agents for Hypertension

Haveles (pp. 197-200) (Fig. 15-6)Haveles (pp. 197-200) (Fig. 15-6) The three major types of diuretics are foundThe three major types of diuretics are found

Thiazides (-like) diureticsThiazides (-like) diuretics Loop diureticsLoop diuretics Potassium-sparing diureticsPotassium-sparing diuretics


Thiazide DiureticsThiazide Diuretics

Haveles (pp. 197, 199-200)Haveles (pp. 197, 199-200) Among the most common agents for Among the most common agents for

treatment of hypertensiontreatment of hypertension hydrochlorothiazide (HCTZ) is the most commonly hydrochlorothiazide (HCTZ) is the most commonly

used thiazideused thiazide Many patients with stage 1 hypertension are Many patients with stage 1 hypertension are

treated solely with HCTZtreated solely with HCTZ


Mechanism of Action of Thiazide Mechanism of Action of Thiazide DiureticsDiuretics

Haveles (pp. 197, 199) (Table 15-8)Haveles (pp. 197, 199) (Table 15-8) The exact mechanism by which thiazide The exact mechanism by which thiazide

diuretics lower blood pressure has not been diuretics lower blood pressure has not been determineddetermined Initially inhibit sodium reabsorption from the distal Initially inhibit sodium reabsorption from the distal

convoluted tubule and part of the ascending loop convoluted tubule and part of the ascending loop of Henle of the kidneyof Henle of the kidney

Water and chloride ions passively accompany the Water and chloride ions passively accompany the sodium, producing diuresissodium, producing diuresis

Potassium excretion is also increasedPotassium excretion is also increased


Adverse Reactions of Thiazide Adverse Reactions of Thiazide DiureticsDiuretics

Haveles (pp. 199-200) (Table 15-9)Haveles (pp. 199-200) (Table 15-9) Common adverse reactions include Common adverse reactions include

hypokalemia (secondary to sodium-potassium hypokalemia (secondary to sodium-potassium exchange) and hyperuricemia (inhibits uric exchange) and hyperuricemia (inhibits uric acid secretion)acid secretion) Hyperglycemia, hyperlipidemia, hypercalcemia, and Hyperglycemia, hyperlipidemia, hypercalcemia, and

anorexia are other side effectsanorexia are other side effects Hyperuricemia is of special concern if the patient Hyperuricemia is of special concern if the patient

has gouthas gout



Adverse Reactions of Thiazide Adverse Reactions of Thiazide DiureticsDiuretics

Oral adverse reactions include xerostomia and, rarely, Oral adverse reactions include xerostomia and, rarely, oral lichenoid eruptions indistinguishable from lichen oral lichenoid eruptions indistinguishable from lichen planusplanus

Nonsteroidal antiinflammatory drugs (NSAIDs) can Nonsteroidal antiinflammatory drugs (NSAIDs) can reduce the antihypertensive effect of the thiazide reduce the antihypertensive effect of the thiazide diureticsdiuretics

Thiazides can cause hypokalemia and can sensitize Thiazides can cause hypokalemia and can sensitize the myocardium to developing arrhythmiasthe myocardium to developing arrhythmias The potential for arrhythmias is exacerbated in patients The potential for arrhythmias is exacerbated in patients

taking digoxin, especially if digitalis toxicity is presenttaking digoxin, especially if digitalis toxicity is present Epinephrine also has arrhythmic potential; limit to cardiac Epinephrine also has arrhythmic potential; limit to cardiac

dose when patient is taking thiazide diuretics and digitalis dose when patient is taking thiazide diuretics and digitalis toxicity may be presenttoxicity may be present


Examples of Thiazide DiureticsExamples of Thiazide Diuretics

Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4) chlorothiazide (Diuril)chlorothiazide (Diuril) hydrochlorothiazide (HCTZ, Esidrix)hydrochlorothiazide (HCTZ, Esidrix)


Loop Diuretics Loop Diuretics

Haveles (p. 200)Haveles (p. 200) The “strong cousins of thiazides”The “strong cousins of thiazides” furosemide (Lasix) is the most commonly furosemide (Lasix) is the most commonly

used loop diureticused loop diuretic Acts on the ascending limb of the loop of Henle Acts on the ascending limb of the loop of Henle

and has some effect on the distal tubuleand has some effect on the distal tubule Inhibits reabsorption of sodium with concurrent Inhibits reabsorption of sodium with concurrent

loss of fluidsloss of fluids



Loop DiureticsLoop Diuretics

Side effects include hypokalemia and Side effects include hypokalemia and hyperuricemiahyperuricemia

Used in management of hypertensive patients Used in management of hypertensive patients with CHFwith CHF Can be used when rapid diuresis is desiredCan be used when rapid diuresis is desired


Examples of Loop DiureticsExamples of Loop Diuretics

Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4) bumetanide (Bumex)bumetanide (Bumex) furosemide (Lasix)furosemide (Lasix) torsemide (Demadex)torsemide (Demadex)


Potassium-Sparing Diuretics Potassium-Sparing Diuretics

Haveles (p. 200)Haveles (p. 200) ““Puny” diuretics with “potassium-catching” Puny” diuretics with “potassium-catching”

ability (weak diuretic action)ability (weak diuretic action) Spironolactone: competitively antagonizes the Spironolactone: competitively antagonizes the

action of aldosterone action of aldosterone • Result is sodium excretion through diuresis and loss of Result is sodium excretion through diuresis and loss of

fluid volumefluid volume

Triamterene: interferes with potassium-sodium Triamterene: interferes with potassium-sodium exchange in the distal and cortical collecting exchange in the distal and cortical collecting tubules and the collecting duct by inhibiting sodium-tubules and the collecting duct by inhibiting sodium-potassium adenosine triphosphate (ATPase)potassium adenosine triphosphate (ATPase)


Examples of Potassium-Sparing Examples of Potassium-Sparing DiureticsDiuretics

Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4) amiloride (Midamor)amiloride (Midamor) spironolactone (Aldactone)spironolactone (Aldactone) triamterene (Dyrenium)triamterene (Dyrenium) eplerenone (Inspra)eplerenone (Inspra)


Potassium SaltsPotassium Salts

Haveles (p. 200)Haveles (p. 200) Potassium salts are not cardiac drugsPotassium salts are not cardiac drugs

Lack of potassium caused by diuretics must be Lack of potassium caused by diuretics must be managed, often with potassium supplementationmanaged, often with potassium supplementation

The most common adverse reaction relates to The most common adverse reaction relates to the GI tract; includes nausea and abdominal the GI tract; includes nausea and abdominal discomfortdiscomfort

Patients taking calcium salts should be Patients taking calcium salts should be questioned about their use of diureticsquestioned about their use of diuretics


ββ-Adrenergic Blocking Agents for -Adrenergic Blocking Agents for HypertensionHypertension

Haveles (pp. 200-201)Haveles (pp. 200-201) ββ-Adrenergic blockers are frequently used to -Adrenergic blockers are frequently used to

treat hypertensiontreat hypertension ββ11-receptor stimulation is associated with increased -receptor stimulation is associated with increased

heart rate, cardiac contractility, and AV conductionheart rate, cardiac contractility, and AV conduction ββ22-receptor stimulation causes vasodilation of -receptor stimulation causes vasodilation of

skeletal muscle and bronchodilation in pulmonary skeletal muscle and bronchodilation in pulmonary tissuestissues

ββ-Adrenergic blockers inhibit these actions-Adrenergic blockers inhibit these actionscont’d…cont’d…



Haveles (pp. 196, 201) (Box 15-4)Haveles (pp. 196, 201) (Box 15-4) Nonselective Nonselective ββ-adrenergic blocking drugs such as -adrenergic blocking drugs such as

propranolol, block both propranolol, block both ββ11- and - and ββ22-receptors-receptors In usual doses selective In usual doses selective ββ-adrenergic blocking -adrenergic blocking

drugs such as metoprolol, block drugs such as metoprolol, block ββ11-receptors more -receptors more

than than ββ22-receptors (-receptors (ββ1 1 > > ββ22 ) ) At larger doses, the selectivity disappearsAt larger doses, the selectivity disappears

• Pindolol and acebutolol have partial agonist activity Pindolol and acebutolol have partial agonist activity and cause some beta stimulation while blocking and cause some beta stimulation while blocking catecholamine actioncatecholamine action




Haveles (pp. 200-201)Haveles (pp. 200-201) ββ-Adrenergic blockers lower blood pressure -Adrenergic blockers lower blood pressure

by decreasing cardiac outputby decreasing cardiac output Side effects: bradycardia, mental depression, and Side effects: bradycardia, mental depression, and

decreased sexual abilitydecreased sexual ability CNS effects: confusion, hallucinations, dizziness, CNS effects: confusion, hallucinations, dizziness,

and fatigue have been reportedand fatigue have been reported GI tract effects: diarrhea, nausea, and vomitingGI tract effects: diarrhea, nausea, and vomiting Can produce xerostomia (very mild) or worsen a Can produce xerostomia (very mild) or worsen a

patient’s lipid profilepatient’s lipid profile May exacerbate asthma, angina, or peripheral May exacerbate asthma, angina, or peripheral

vascular diseasevascular disease


Dental Drug Interactions of Dental Drug Interactions of ββ--Adrenergic Blocking Agents Adrenergic Blocking Agents

Haveles (p. 201)Haveles (p. 201) Nonselective Nonselective ββ-blockers can have a drug -blockers can have a drug

interaction with epinephrine interaction with epinephrine May have a two- to fourfold increase in vasopressor May have a two- to fourfold increase in vasopressor

response resulting in hypertensionresponse resulting in hypertension In patients with cardiovascular disease or higher In patients with cardiovascular disease or higher

blood pressure, the amount of epinephrine given blood pressure, the amount of epinephrine given to patients taking nonspecific to patients taking nonspecific ββ-blockers should be -blockers should be limited to the cardiac dose unless blood pressure limited to the cardiac dose unless blood pressure monitoring accompanies the use of larger dosesmonitoring accompanies the use of larger doses Usual doses can be given to patients taking specific Usual doses can be given to patients taking specific ββ--

blockers or blockers or αα- and - and ββ-blockers-blockers


αα- and - and ββ-Adrenergic Blocking -Adrenergic Blocking Drug for HypertensionDrug for Hypertension

Haveles (p. 201)Haveles (p. 201) Labetalol is a nonselective Labetalol is a nonselective ββ-adrenergic -adrenergic

receptor blocking drug that also has receptor blocking drug that also has αα--receptor blocking activityreceptor blocking activity Reduces peripheral resistance through its Reduces peripheral resistance through its αα--

blocking actionblocking action


Examples of Examples of ββ-Adrenergic -Adrenergic Blocking Agents for HypertensionBlocking Agents for Hypertension

Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4) ββ-Adrenergic blockers-Adrenergic blockers

atenolol (Tenormin)atenolol (Tenormin) betaxolol (Kerlone)betaxolol (Kerlone) bisoprolol (Zebeta)bisoprolol (Zebeta) metoprolol (Lopressor) (Toprol-XL)metoprolol (Lopressor) (Toprol-XL) nadolol (Corgard)nadolol (Corgard) propranolol (Inderal [LA])propranolol (Inderal [LA]) timolol (Blocadren)timolol (Blocadren)



Examples of Examples of ββ-Adrenergic -Adrenergic Blocking Agents for HypertensionBlocking Agents for Hypertension ββ-Blockers with intrinsic sympathomimetic -Blockers with intrinsic sympathomimetic

activityactivity acebutolol (Sectral)acebutolol (Sectral) penbutolol (Levatol)penbutolol (Levatol) pindolol (Visken)pindolol (Visken)

ββ-Blockers with -Blockers with α-α-blocking activity blocking activity carvedilol (Coreg)carvedilol (Coreg) labetalol (Normodyne, Trandate)labetalol (Normodyne, Trandate)


Calcium Channel Blocking Calcium Channel Blocking Agents for HypertensionAgents for Hypertension

Haveles (pp. 201-202)Haveles (pp. 201-202) Many CCBs end in the suffix -Many CCBs end in the suffix -dipinedipine

Used to treat hypertension and other cardiac Used to treat hypertension and other cardiac conditions such as arrhythmias and anginaconditions such as arrhythmias and angina


Mechanism of Calcium Channel Mechanism of Calcium Channel Blocking AgentsBlocking Agents

Haveles (p. 201)Haveles (p. 201) Inhibit the movement of extracellular calcium Inhibit the movement of extracellular calcium

ions into cells, including vascular smooth-ions into cells, including vascular smooth-muscle and cardiac cellsmuscle and cardiac cells Produces vasodilation, which produces coronary Produces vasodilation, which produces coronary

vasodilation and reverses vasospasmsvasodilation and reverses vasospasms By producing systemic vasodilation CCBs reduce By producing systemic vasodilation CCBs reduce

the afterload on the heartthe afterload on the heart Useful in treatment of both angina pectoris and Useful in treatment of both angina pectoris and

hypertensionhypertensioncont’d…cont’d…


Mechanism of Calcium Channel Mechanism of Calcium Channel Blocking AgentsBlocking Agents

At least four types of calcium channels (L, T, At least four types of calcium channels (L, T, N, and P) have been discoveredN, and P) have been discovered Current CCBs are all of the L typeCurrent CCBs are all of the L type

The decrease in transmembrane calcium The decrease in transmembrane calcium current results in relaxation of vascular current results in relaxation of vascular smooth-muscle cells and a reduction in smooth-muscle cells and a reduction in cardiac contractility and conductioncardiac contractility and conduction


Pharmacologic Effects of Calcium Pharmacologic Effects of Calcium Channel Blocking Agents for Channel Blocking Agents for

HypertensionHypertension Haveles (p. 201)Haveles (p. 201)

Smooth muscle: vascular smooth muscle is Smooth muscle: vascular smooth muscle is relaxed and dilation of coronary and peripheral relaxed and dilation of coronary and peripheral arteries and arterioles occur, reducing preload arteries and arterioles occur, reducing preload

Cardiac muscle: may reduce heart rate, Cardiac muscle: may reduce heart rate, decrease myocardial contractility (negative decrease myocardial contractility (negative inotropic effect), and slow AV nodal conductioninotropic effect), and slow AV nodal conduction


Adverse Reactions of Calcium Adverse Reactions of Calcium Channel Blocking AgentsChannel Blocking Agents

Haveles (pp. 201-202)Haveles (pp. 201-202) Extensions of pharmacologic effectsExtensions of pharmacologic effects

CNS: can produce excessive hypotension, which CNS: can produce excessive hypotension, which can cause dizziness and lightheadedness, can cause dizziness and lightheadedness, headacheheadache

GI: nausea, vomiting, and constipationGI: nausea, vomiting, and constipation Cardiovascular: bradycardia and edemaCardiovascular: bradycardia and edema Other: shortness of breath due to pulmonary Other: shortness of breath due to pulmonary

edema has been reportededema has been reported


Oral Manifestations of Calcium Oral Manifestations of Calcium Channel Blocking AgentsChannel Blocking Agents

Haveles (p. 202)Haveles (p. 202) Include xerostomia, dysgeusia, gingival Include xerostomia, dysgeusia, gingival

enlargementenlargement On discontinuation of the CCB, the gingival On discontinuation of the CCB, the gingival

enlargement usually reverts to normal tissue and enlargement usually reverts to normal tissue and does not reappeardoes not reappear

If not, gingivectomy or gingivoplasty may be If not, gingivectomy or gingivoplasty may be requiredrequired


Dental Drug Interactions of Calcium Dental Drug Interactions of Calcium Channel Blocking AgentsChannel Blocking Agents

Haveles (p. 202)Haveles (p. 202) carbamazepine (Tegretol) is used for carbamazepine (Tegretol) is used for

trigeminal neuralgiatrigeminal neuralgia Diltiazem and verapamil may increase serum Diltiazem and verapamil may increase serum

levels of carbamazepine, resulting in toxicitylevels of carbamazepine, resulting in toxicity Both nausea and constipation, side effects of Both nausea and constipation, side effects of

CCBs, could be additive with side effects CCBs, could be additive with side effects produced by NSAIDs (nausea) and opioids produced by NSAIDs (nausea) and opioids (constipation)(constipation)


Examples of Calcium Channel Examples of Calcium Channel Blocking AgentsBlocking Agents

Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4) CCBsCCBs

diltiazem (Cardizem [SR], Dilacor [XR])diltiazem (Cardizem [SR], Dilacor [XR]) verapamil (Isoptin [SR], Calan [SR])verapamil (Isoptin [SR], Calan [SR])

DihydropyridinesDihydropyridines amlodipine (Norvasc)amlodipine (Norvasc) felodipine (Plendil)felodipine (Plendil) isradipine (DynaCirc)isradipine (DynaCirc) nicardipine (Cardene [SR])nicardipine (Cardene [SR]) nifedipine (Procardia [XL], Adalat [CC])nifedipine (Procardia [XL], Adalat [CC]) nisoldipine (Sular)nisoldipine (Sular)


Angiotensin-Related AgentsAngiotensin-Related Agents

Haveles (pp. 202-203)Haveles (pp. 202-203) Two types of drugs whose mechanism involves Two types of drugs whose mechanism involves

angiotensin angiotensin ACEIsACEIs ARBsARBs


Angiotensin-Converting Enzyme Angiotensin-Converting Enzyme InhibitorsInhibitors

Haveles (pp. 202-203)Haveles (pp. 202-203) ACEIs prevent the conversion of angiotensin I ACEIs prevent the conversion of angiotensin I

to angiotensin IIto angiotensin II ACEI drugs are commonly used as ACEI drugs are commonly used as

antihypertensivesantihypertensives Many ACEIs end in Many ACEIs end in -pril-pril


Mechanism of Mechanism of Angiotensin-Angiotensin-Converting Enzyme Converting Enzyme InhibitorsInhibitors

Haveles (p. 202) (Fig. 15-7)Haveles (p. 202) (Fig. 15-7) The renin-angiotensin-aldosterone system The renin-angiotensin-aldosterone system

adjusts the quantity of sodium and water adjusts the quantity of sodium and water retained (circulatory volume) and the peripheral retained (circulatory volume) and the peripheral resistance (blood vessels)resistance (blood vessels) When the kidney senses a decrease in blood When the kidney senses a decrease in blood

pressure or flow it releases reninpressure or flow it releases renin Renin catalyzes the conversion of angiotensinogen Renin catalyzes the conversion of angiotensinogen

(inactive precursor) to angiotensin I(inactive precursor) to angiotensin I ACE converts angiotensin I to angiotensin IIACE converts angiotensin I to angiotensin II

ACE is the enzyme blocked by ACEIsACE is the enzyme blocked by ACEIscont’d…cont’d…


Mechanism of Mechanism of Angiotensin-Angiotensin-Converting Enzyme Converting Enzyme InhibitorsInhibitors

Angiotensin II produces vasoconstriction and Angiotensin II produces vasoconstriction and stimulates the adrenal cortex to release stimulates the adrenal cortex to release aldosterone, facilitating water retentionaldosterone, facilitating water retention By blocking these events, blood pressure is By blocking these events, blood pressure is

loweredlowered


Adverse Reactions of Adverse Reactions of Angiotensin-Angiotensin-Converting Enzyme Converting Enzyme InhibitorsInhibitors

Haveles (pp. 202-203) (Box 15-6)Haveles (pp. 202-203) (Box 15-6) The most common adverse reactions are related The most common adverse reactions are related

to the cardiovascular system and the CNSto the cardiovascular system and the CNS Cardiovascular: hypotension has produced dizziness, Cardiovascular: hypotension has produced dizziness,

lightheadedness, and faintinglightheadedness, and fainting• Tachycardia and chest pain have been notedTachycardia and chest pain have been noted

CNS: side effects may include dizziness, insomnia, CNS: side effects may include dizziness, insomnia, fatigue, and headachefatigue, and headache



Adverse Reactions of Adverse Reactions of Angiotensin-Angiotensin-Converting Enzyme Converting Enzyme InhibitorsInhibitors Haveles (pp. 202-203) (Box 15-6)Haveles (pp. 202-203) (Box 15-6)

GI: nausea, vomiting, and diarrhea can occurGI: nausea, vomiting, and diarrhea can occur Respiratory: an increase in upper respiratory Respiratory: an increase in upper respiratory

symptoms, including a dry, hacking cough symptoms, including a dry, hacking cough can occurcan occur It occurs because the ACE also inactivates It occurs because the ACE also inactivates

bradykinin, a potent stimulator of allergic reactionsbradykinin, a potent stimulator of allergic reactions



Adverse Reactions of Adverse Reactions of Angiotensin-Angiotensin-Converting Enzyme Converting Enzyme InhibitorsInhibitors

Allergic-like reactionsAllergic-like reactions Angioedema: swelling of the extremities, face, lips, Angioedema: swelling of the extremities, face, lips,

mucous membranes, tongue, glottis, or larynx can mucous membranes, tongue, glottis, or larynx can occuroccur

RashRash Other: because teratogenicity can cause fetal Other: because teratogenicity can cause fetal

and neonatal morbidity and mortality, ACEIs and neonatal morbidity and mortality, ACEIs should not be given to women who could be or should not be given to women who could be or become pregnantbecome pregnant


Oral Adverse Reactions of Oral Adverse Reactions of Angiotensin-Converting Enzyme Angiotensin-Converting Enzyme

InhibitorsInhibitors Haveles (pp. 202-203)Haveles (pp. 202-203)

Dysgeusia: an altered sense of taste is reported Dysgeusia: an altered sense of taste is reported in about 6% of patients taking captoprilin about 6% of patients taking captopril Usually reversible after a few months, even with Usually reversible after a few months, even with

continued drug treatmentcontinued drug treatment Autoimmune oral lesions: lichenoid or Autoimmune oral lesions: lichenoid or

pemphigoid reactions may produce oral pemphigoid reactions may produce oral manifestationsmanifestations May have a photosensitivity factorMay have a photosensitivity factor


Dental Drug Interactions of Dental Drug Interactions of Angiotensin-Converting Enzyme Angiotensin-Converting Enzyme

InhibitorsInhibitors Haveles (p. 203)Haveles (p. 203)

The antihypertensive effectiveness of ACEIs is The antihypertensive effectiveness of ACEIs is reduced by administration of the NSAIDsreduced by administration of the NSAIDs Chronic administration for several days may result in Chronic administration for several days may result in

an increase in the patient’s blood pressurean increase in the patient’s blood pressure ACEIs may be used alone or in combination with ACEIs may be used alone or in combination with

a a ββ-blocker, thiazide diuretic, or CCB-blocker, thiazide diuretic, or CCB


Examples of Examples of Angiotensin-Converting Angiotensin-Converting Enzyme Enzyme Inhibitors for HypertensionInhibitors for Hypertension

Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4) benazepril (Lotensin)benazepril (Lotensin) captopril (Capoten) captopril (Capoten) enalapril (Vasotec) enalapril (Vasotec) fosinopril (Monopril)fosinopril (Monopril) lisinopril lisinopril ((Zestril, Prinivil)Zestril, Prinivil) moexipril (Univasc)moexipril (Univasc) perindopril (Aceon)perindopril (Aceon) quinapril (Accupril)quinapril (Accupril) ramipril (Altace)ramipril (Altace) trandolapril (Mavik)trandolapril (Mavik)


Angiotensin Receptor BlockersAngiotensin Receptor Blockers

Haveles (p. 203)Haveles (p. 203) ARBs attach to the angiotensin II receptor ARBs attach to the angiotensin II receptor

and block the effect of angiotensin IIand block the effect of angiotensin II losartan (Cozaar) is the prototypelosartan (Cozaar) is the prototype

losartan a high affinity and selectivity for the ATlosartan a high affinity and selectivity for the AT11--

receptorreceptor It blocks the vasoconstrictor and aldosterone-It blocks the vasoconstrictor and aldosterone-

secreting effects of angiotensin IIsecreting effects of angiotensin II An increase in plasma renin level followsAn increase in plasma renin level follows


Adverse Reactions of Adverse Reactions of Angiotensin Receptor BlockersAngiotensin Receptor Blockers

Haveles (p. 203)Haveles (p. 203) ARBs are more specific than ACEIs and may be ARBs are more specific than ACEIs and may be

expected to have fewer adverse reactionsexpected to have fewer adverse reactions CNS: effects can include dizziness, fatigue, insomnia, and CNS: effects can include dizziness, fatigue, insomnia, and

headacheheadache Upper respiratory infections occur more often in patients Upper respiratory infections occur more often in patients

taking losartantaking losartan GI: losartan can produce diarrheaGI: losartan can produce diarrhea Pain: both muscle cramps and leg and back pain have Pain: both muscle cramps and leg and back pain have

been reported with losartanbeen reported with losartan Angioedema can occur, rarelyAngioedema can occur, rarely Teratogenicity can occur if losartan is administered to Teratogenicity can occur if losartan is administered to

pregnant womenpregnant women


Dental Drug Interactions of Dental Drug Interactions of Angiotensin Receptor BlockersAngiotensin Receptor Blockers Haveles (p. 203)Haveles (p. 203)

NSAIDs may antagonize the antihypertensive NSAIDs may antagonize the antihypertensive effect of losartan by inhibiting renal effect of losartan by inhibiting renal prostaglandin synthesis or causing sodium prostaglandin synthesis or causing sodium and fluid retentionand fluid retention


Examples of Angiotensin Examples of Angiotensin Receptor BlockersReceptor Blockers

Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4) candesartan (Atacand)candesartan (Atacand) eprosartan (Tevetan)eprosartan (Tevetan) irbesartan (Avapro)irbesartan (Avapro) losartan (Cozaar)losartan (Cozaar) olmesartan (Benicar)olmesartan (Benicar) telmisartan (Micardis)telmisartan (Micardis) valsartan (Diovan)valsartan (Diovan)


Renin InhibitorsRenin Inhibitors

Haveles (p. 203)Haveles (p. 203) aliskiren (Tekturna): the first of a new class of aliskiren (Tekturna): the first of a new class of

drugs approved by the U.S Food and Drug drugs approved by the U.S Food and Drug Administration for treatment of hypertensionAdministration for treatment of hypertension Works by binding to renin which then reduces the Works by binding to renin which then reduces the

levels of angiotensin I, angiotensin II, and levels of angiotensin I, angiotensin II, and aldosteronealdosterone


αα11-Adrenergic Blocking Agents -Adrenergic Blocking Agents

for Hypertensionfor Hypertension Haveles (p. 204)Haveles (p. 204)

The adrenergic blockers include the The adrenergic blockers include the αα--blockers and blockers and ββ-blockers previously described-blockers previously described Two Two αα-receptor subtypes have been identified, -receptor subtypes have been identified, αα11

and and αα22


Mechanism of Mechanism of αα11-Adrenergic -Adrenergic

Blocking Agents for HypertensionBlocking Agents for Hypertension

αα11-Receptors, located on postsynaptic receptor -Receptors, located on postsynaptic receptor

tissues, produce vasoconstriction and increase tissues, produce vasoconstriction and increase peripheral resistance when stimulatedperipheral resistance when stimulated αα11-Blocking agents produce peripheral vasodilation in -Blocking agents produce peripheral vasodilation in

the arterioles and venules that decreases peripheral the arterioles and venules that decreases peripheral vascular resistancevascular resistance

αα11-Adrenergic blockers result in a reduction in urethral -Adrenergic blockers result in a reduction in urethral

resistance and pressure, bladder outlet resistance, resistance and pressure, bladder outlet resistance, and urinary symptomsand urinary symptoms

Used in management of older men who have an Used in management of older men who have an enlarged prostate glandenlarged prostate gland


Adverse Reactions of Adverse Reactions of αα11-Adrenergic -Adrenergic

Blocking Agents for HypertensionBlocking Agents for Hypertension Haveles (p. 204)Haveles (p. 204)

Orthostatic hypotension: can result in Orthostatic hypotension: can result in dizziness or syncopedizziness or syncope

CNS: CNS: αα11-adrenergic blockers can cause CNS -adrenergic blockers can cause CNS

depression, producing either drowsiness or depression, producing either drowsiness or excitation and headacheexcitation and headache

Cardiovascular: tachycardia, arrhythmias, Cardiovascular: tachycardia, arrhythmias, and palpitations can occurand palpitations can occur Peripheral edema is another side effectPeripheral edema is another side effect


Dental Drug Interactions of Dental Drug Interactions of αα11--

Adrenergic Blocking Agents for Adrenergic Blocking Agents for HypertensionHypertension

Haveles (p. 204) (Box 15-7)Haveles (p. 204) (Box 15-7) NSAIDs, especially indomethacin, can reduce NSAIDs, especially indomethacin, can reduce

antihypertensive effect of the antihypertensive effect of the αα11-blockers-blockers Inhibit renal prostaglandin synthesis or cause sodium Inhibit renal prostaglandin synthesis or cause sodium

and fluid retentionand fluid retention



Dental Drug Interactions of Dental Drug Interactions of αα11--

Adrenergic Blocking Agents for Adrenergic Blocking Agents for HypertensionHypertension

Haveles (p. 204) (Box 15-7)Haveles (p. 204) (Box 15-7) Epinephrine: sympathomimetics can increase Epinephrine: sympathomimetics can increase

the antihypertensive effect of doxazosinthe antihypertensive effect of doxazosin αα11-Blockers prevent -Blockers prevent αα11-agonist effects -agonist effects

(vasoconstriction) of epinephrine, leaving the (vasoconstriction) of epinephrine, leaving the ββ11--

agonist and agonist and ββ22-agonist effects (vasodilation) to -agonist effects (vasodilation) to

predominatepredominate Can result in severe hypotension and reflex Can result in severe hypotension and reflex

tachycardiatachycardia


Uses Uses of of αα11-Adrenergic Blocking -Adrenergic Blocking

Agents for HypertensionAgents for Hypertension Haveles (p. 204)Haveles (p. 204)

Both doxazosin and terazosin are indicated Both doxazosin and terazosin are indicated for the management of benign prostatic for the management of benign prostatic hypertrophy (BPH) in addition to the hypertrophy (BPH) in addition to the treatment of hypertensiontreatment of hypertension


Examples of Examples of αα11-Receptor Antagonists -Receptor Antagonists

(Blockers) for Hypertension(Blockers) for Hypertension Haveles (p. 196) (Box 15-4)Haveles (p. 196) (Box 15-4)

doxazosin (Cardura)doxazosin (Cardura) prazosin (Minipress)prazosin (Minipress) terazosin (Hytrin)terazosin (Hytrin)


Other Antihypertensive AgentsOther Antihypertensive Agents

Haveles (p. 204)Haveles (p. 204) These antihypertensive agents are used less These antihypertensive agents are used less

often than those previously described often than those previously described because they generally have more or less because they generally have more or less tolerated adverse reactionstolerated adverse reactions ClonidineClonidine Other centrally acting antihypertensive agentsOther centrally acting antihypertensive agents

• GuanethidineGuanethidine

• ReserpineReserpine

• HydralazineHydralazine


clonidineclonidine(Catapres)(Catapres)

Haveles (p. 204)Haveles (p. 204) A CNS-mediated (centrally acting) A CNS-mediated (centrally acting)

antihypertensive drug that reduces peripheral antihypertensive drug that reduces peripheral resistance through a CNS-mediated action on the resistance through a CNS-mediated action on the αα-receptor-receptor Stimulation of presynaptic central Stimulation of presynaptic central αα22-adrenergic -adrenergic

receptors results in decreased sympathetic outflowreceptors results in decreased sympathetic outflow Reduces heart rate, cardiac output, and total peripheral Reduces heart rate, cardiac output, and total peripheral

resistanceresistance May be administered orally or by transdermal May be administered orally or by transdermal

patchpatch


Adverse Reactions of ClonidineAdverse Reactions of Clonidine

Haveles (p. 204)Haveles (p. 204) Include a high incidence of sedation and Include a high incidence of sedation and

dizzinessdizziness Rapid elevation of blood pressure has occurred Rapid elevation of blood pressure has occurred

with abrupt discontinuationwith abrupt discontinuation CNS depressants employed in dental CNS depressants employed in dental

conscious-sedation techniques may conscious-sedation techniques may contribute to postural hypotension when used contribute to postural hypotension when used in a patient taking clonidinein a patient taking clonidine


Oral Effects of ClonidineOral Effects of Clonidine

Haveles (p. 204)Haveles (p. 204) A high incidence of xerostomia (40%), parotid A high incidence of xerostomia (40%), parotid

gland swelling, and paingland swelling, and pain Another side effect is dysgeusiaAnother side effect is dysgeusia


Other Centrally Acting Other Centrally Acting Antihypertensive AgentsAntihypertensive Agents

Haveles (pp. 204-205)Haveles (pp. 204-205) Two other centrally acting antihypertensive Two other centrally acting antihypertensive

agents are also availableagents are also available methyldopa (Aldomet) and guanabenz (Wytensin)methyldopa (Aldomet) and guanabenz (Wytensin)

Adverse effects and indications are similar to Adverse effects and indications are similar to clonidineclonidine May be combined with diuretics in essential May be combined with diuretics in essential

hypertension managementhypertension management


guanethidineguanethidine(Ismelin)(Ismelin)

Haveles (pp. 198, 204-205) (Fig. 15-5)Haveles (pp. 198, 204-205) (Fig. 15-5) Severe adverse reactions severely limits its useSevere adverse reactions severely limits its use Blocks the release of norepinephrine from the Blocks the release of norepinephrine from the

sympathetic nerve endingssympathetic nerve endings Also depletes the amount of norepinephrine stored in Also depletes the amount of norepinephrine stored in

synaptic vesiclessynaptic vesicles Reduces sympathetic nervous system tone and Reduces sympathetic nervous system tone and

decreases blood pressuredecreases blood pressure Causes severe postural and exertional Causes severe postural and exertional

hypotensionhypotension


ReserpineReserpine

Haveles (p. 205)Haveles (p. 205) Depletes norepinephrine from the sympathetic Depletes norepinephrine from the sympathetic

nerve endingsnerve endings Adverse effects include diarrhea, bad dreams, Adverse effects include diarrhea, bad dreams,

sedation, and even psychic depression leading sedation, and even psychic depression leading to suicideto suicide

Aggravates peptic ulcersAggravates peptic ulcers


hydralazinehydralazine(Apresoline)(Apresoline)

Haveles (p. 205)Haveles (p. 205) Acts directly on arterioles to reduce peripheral Acts directly on arterioles to reduce peripheral

resistance (vasodilation)resistance (vasodilation) At the same time a rise in heart rate and output At the same time a rise in heart rate and output

occursoccurs Propranolol is often administered concurrently to Propranolol is often administered concurrently to

reduce the tachycardia and increased cardiac outputreduce the tachycardia and increased cardiac output Side effects include cardiac arrhythmias, Side effects include cardiac arrhythmias,

angina, headache, and dizzinessangina, headache, and dizziness The drug of choice for treatment of a pregnant The drug of choice for treatment of a pregnant

hypertensive womanhypertensive woman


Management of the Dental Patient Management of the Dental Patient Taking Antihypertensive AgentsTaking Antihypertensive Agents

Haveles (p. 205) (Box 15-8)Haveles (p. 205) (Box 15-8) Check for xerostomia and its managementCheck for xerostomia and its management If taking a CCB, check for gingival enlargementIf taking a CCB, check for gingival enlargement Check blood pressure before each appointmentCheck blood pressure before each appointment Avoid dental agents that add to side effects Avoid dental agents that add to side effects

such as opioidssuch as opioids If on diuretics, check for symptoms of If on diuretics, check for symptoms of

hypokalemia, which may exacerbate hypokalemia, which may exacerbate arrhythmias from epinephrinearrhythmias from epinephrine

If taking an ACEI, check for symptoms of If taking an ACEI, check for symptoms of neutropenianeutropenia



Management of the Dental Patient Management of the Dental Patient Taking Antihypertensive AgentsTaking Antihypertensive Agents

Haveles (p. 205)Haveles (p. 205) Adverse reactionsAdverse reactions

XerostomiaXerostomia DysgeusiaDysgeusia Gingival enlargementGingival enlargement Orthostatic hypotensionOrthostatic hypotension ConstipationConstipation Central nervous system sedationCentral nervous system sedation


Antihyperlipidemic AgentsAntihyperlipidemic Agents

Haveles (pp. 205-207)Haveles (pp. 205-207) 3-Hydroxy-3-methylglutaryl coenzyme A (HMG 3-Hydroxy-3-methylglutaryl coenzyme A (HMG

CoA) reductase inhibitorsCoA) reductase inhibitors NiacinNiacin CholestyramineCholestyramine GemfibrozilGemfibrozil Dental ImplicationsDental Implications



Antihyperlipidemic AgentsAntihyperlipidemic Agents Haveles (p. 205)Haveles (p. 205)

Hyperlipidemia and hyperlipoproteinemia are Hyperlipidemia and hyperlipoproteinemia are elevations of plasma lipid concentrations above elevations of plasma lipid concentrations above accepted normal valuesaccepted normal values These metabolic distortions include elevations in These metabolic distortions include elevations in

cholesterol and/or triglycerides and are associated with cholesterol and/or triglycerides and are associated with the development of arteriosclerosisthe development of arteriosclerosis

Many different types of hyperlipoproteinemias may Many different types of hyperlipoproteinemias may result in elevations of chylomicrons, very-low-density result in elevations of chylomicrons, very-low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), or lipoproteins (VLDLs), low-density lipoproteins (LDLs), or combinations of thesecombinations of these




Foam cells, more prevalent in uncontrolled Foam cells, more prevalent in uncontrolled diabetes, become filled with cholesterol estersdiabetes, become filled with cholesterol esters Accumulation of esters leads to deposition of lipids in Accumulation of esters leads to deposition of lipids in

arteriesarteries Collagen and fibrin also accumulate, occluding the Collagen and fibrin also accumulate, occluding the

vesselsvessels Atherosclerosis can lead to coronary artery Atherosclerosis can lead to coronary artery

disease, myocardial infarction, and cerebral disease, myocardial infarction, and cerebral artery diseaseartery disease Endothelium over the plaques activates platelets Endothelium over the plaques activates platelets

leading to formation of thrombi and clinical symptomsleading to formation of thrombi and clinical symptomscont’d…cont’d…



Haveles (p. 205)Haveles (p. 205) Cholesterol and other plasma lipids are Cholesterol and other plasma lipids are

carried in the blood as protein complexes to carried in the blood as protein complexes to make them more soluble in plasmamake them more soluble in plasma LDLs carry the greatest concentration of LDLs carry the greatest concentration of

cholesterol and are considered to be the most cholesterol and are considered to be the most dangerousdangerous

High-density lipoproteins (HDLs) carry the least High-density lipoproteins (HDLs) carry the least cholesterol and are considered to be beneficialcholesterol and are considered to be beneficial




Haveles (pp. 205-206) (Table 15-12)Haveles (pp. 205-206) (Table 15-12) The first line of treatment is increasing The first line of treatment is increasing

exercise and decreasing saturated fat and exercise and decreasing saturated fat and cholesterol from the dietcholesterol from the diet Drug therapy of hyperlipoproteinemia is directed at Drug therapy of hyperlipoproteinemia is directed at

lowering the level of LDL cholesterollowering the level of LDL cholesterol Some are more specific for cholesterol and some Some are more specific for cholesterol and some

are more specific for triglyceridesare more specific for triglycerides Drugs include bile acid-binding resins, niacin, Drugs include bile acid-binding resins, niacin,

gemfibrozil, and HMG CoA reductase gemfibrozil, and HMG CoA reductase inhibitorsinhibitors


3-Hydroxy-3-Methylglutaryl 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase InhibitorsCoenzyme A Reductase Inhibitors

Haveles (p. 206)Haveles (p. 206) Often called “statins” because generic names Often called “statins” because generic names

end in that suffixend in that suffix lovastatin (Mevacor) is an examplelovastatin (Mevacor) is an example

They lower cholesterol levels by inhibiting They lower cholesterol levels by inhibiting HMG-CoA reductase, the rate-limiting enzyme HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesisin cholesterol synthesis


Adverse Effects of 3-Hydroxy-3-Adverse Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme A Methylglutaryl Coenzyme A

Reductase InhibitorsReductase Inhibitors Haveles (p. 206)Haveles (p. 206)

GI complaints, myositis, skin rash, impotence, GI complaints, myositis, skin rash, impotence, hepatotoxicity, blurred vision, and lens opacitieshepatotoxicity, blurred vision, and lens opacities Myositis results in complaints of muscle painMyositis results in complaints of muscle pain Can increase anticoagulant effect of warfarinCan increase anticoagulant effect of warfarin


Inhibitors of Intestinal Absorption Inhibitors of Intestinal Absorption of Cholesterolof Cholesterol

Haveles (pp. 206-207)Haveles (pp. 206-207) ezetimibe (Zetia): works by inhibiting ezetimibe (Zetia): works by inhibiting

intestinal absorption of cholesterolintestinal absorption of cholesterol Currently comes in combination with simsvastin to Currently comes in combination with simsvastin to

treat cholesterol from two different mechanisms of treat cholesterol from two different mechanisms of actionaction

Side effects include fatigue, abdominal pain, and Side effects include fatigue, abdominal pain, and diarrheadiarrhea


NiacinNiacin

Haveles (p. 207)Haveles (p. 207) OverviewOverview

A B vitamin: in large doses, lowers cholesterol A B vitamin: in large doses, lowers cholesterol levels by inhibiting the secretion of VLDLs without levels by inhibiting the secretion of VLDLs without accumulation of triglycerides in the liveraccumulation of triglycerides in the liver

At larger doses, commonly produces cutaneous At larger doses, commonly produces cutaneous flushing and a sensation of warmth after each flushing and a sensation of warmth after each dosedose• This is blocked by pretreatment with aspirin or ibuprofenThis is blocked by pretreatment with aspirin or ibuprofen

Hyperuricemia, allergic reactions, cholestasis, and Hyperuricemia, allergic reactions, cholestasis, and hepatotoxicity have been reportedhepatotoxicity have been reported


Dental Implications of NiacinDental Implications of Niacin

Haveles (p. 207)Haveles (p. 207) Hypotension may occur as a result of Hypotension may occur as a result of

vasodilationvasodilation


CholestyramineCholestyramine

Haveles (p. 207)Haveles (p. 207) Bile acidBile acid––binding resins lower cholesterol binding resins lower cholesterol

because cholesterol is a precursor required because cholesterol is a precursor required for the synthesis of new bile acidsfor the synthesis of new bile acids When the resins bind with bile acids, they produce When the resins bind with bile acids, they produce

an insoluble product lost through the GI tractan insoluble product lost through the GI tract Bile acids use up cholesterol, thereby reducing Bile acids use up cholesterol, thereby reducing

cholesterol levelscholesterol levels



CholestyramineCholestyramine

Adverse reactions relate to the GI tract and Adverse reactions relate to the GI tract and include constipation and bloatinginclude constipation and bloating Patients often abandon their use Patients often abandon their use


gemfibrozilgemfibrozil(Lopid)(Lopid)

Haveles (p. 207)Haveles (p. 207) Used to treat hyperlipidemias, especially Used to treat hyperlipidemias, especially

when triglycerides are elevatedwhen triglycerides are elevated Increases lipolysis of triglycerides, decreasing Increases lipolysis of triglycerides, decreasing

lipolysis in adipose tissue, and inhibiting secretion lipolysis in adipose tissue, and inhibiting secretion of VLDLs from the liverof VLDLs from the liver



GemfibrozilGemfibrozil

Adverse reactionsAdverse reactions Can promote gallstone formation (cholelithiasis)Can promote gallstone formation (cholelithiasis) Taste perversion and hyperglycemia have been Taste perversion and hyperglycemia have been

reportedreported


Dental Implications of Dental Implications of Antihyperlipidemic AgentsAntihyperlipidemic Agents

Haveles (p. 207)Haveles (p. 207) Patients who take antihyperlipidemic agents Patients who take antihyperlipidemic agents

have a higher risk of atherosclerosis and are have a higher risk of atherosclerosis and are at increased risk for cardiovascular at increased risk for cardiovascular emergencies (not because of the drug but emergencies (not because of the drug but because of the condition for which the drug is because of the condition for which the drug is prescribed)prescribed) GI and liver abnormalities are side effects GI and liver abnormalities are side effects

associated with many of these drugsassociated with many of these drugs


Examples of Antihyperlipidemic Examples of Antihyperlipidemic AgentsAgents

Haveles (p. 206) (Table 15-10)Haveles (p. 206) (Table 15-10) HMG-CoA reductase inhibitors (statins)HMG-CoA reductase inhibitors (statins)

atorvastatin (Lipitor)atorvastatin (Lipitor) fluvastatin (Lescol)fluvastatin (Lescol) lovastatin (Mevacor)lovastatin (Mevacor) pravastatin (Pravachol)pravastatin (Pravachol) simvastatin (Zocor)simvastatin (Zocor)

Bile acid sequestrantsBile acid sequestrants cholestyramine (Questran, Prevalite)cholestyramine (Questran, Prevalite) colestipol (Colestid)colestipol (Colestid)



Examples of Antihyperlipidemic Examples of Antihyperlipidemic AgentsAgents

Haveles (p. 206) (Table 15-10)Haveles (p. 206) (Table 15-10) MiscellaneousMiscellaneous

clofibrate (Atromid-S)clofibrate (Atromid-S) ezetimibe (Zetia)ezetimibe (Zetia) ezetimibe/simvastin (Vytorin)ezetimibe/simvastin (Vytorin) nicotinic acid (Niacin)nicotinic acid (Niacin)

fibratesfibrates fenofibrate (Lipidil-DSC, Tricor)fenofibrate (Lipidil-DSC, Tricor) gemfibrozil (Lopid)gemfibrozil (Lopid)


Drugs that Affect Blood Drugs that Affect Blood CoagulationCoagulation

Haveles (pp. 207-211)Haveles (pp. 207-211) AnticoagulantsAnticoagulants

HemostasisHemostasis WarfarinWarfarin HeparinHeparin ClopidogrelClopidogrel TiclopidineTiclopidine Streptokinase and alteplase Streptokinase and alteplase DipyridamoleDipyridamole PentoxifyllinePentoxifylline

Drugs that increase blood clottingDrugs that increase blood clotting


AnticoagulantsAnticoagulants

Haveles (p. 207)Haveles (p. 207) Drugs that interfere with coagulationDrugs that interfere with coagulation

Administered in an attempt to prevent clottingAdministered in an attempt to prevent clotting Examples of indications for warfarin (Coumadin) Examples of indications for warfarin (Coumadin)

are after a MI or thrombophlebitisare after a MI or thrombophlebitis


HemostasisHemostasis

Haveles (pp. 207-208) (Fig. 15-8) Haveles (pp. 207-208) (Fig. 15-8) Designed to prevent loss of blood after injury Designed to prevent loss of blood after injury

to a blood vesselto a blood vessel Thromboplastin; factors V, VII, and X; and calcium Thromboplastin; factors V, VII, and X; and calcium

ions form prothrombin, thrombin, and finally ions form prothrombin, thrombin, and finally fibrinogen and fibrinfibrinogen and fibrin

Fibrin, along with vascular spasms, platelets, and Fibrin, along with vascular spasms, platelets, and red blood cells quickly forms the clotred blood cells quickly forms the clot




If the blood vessel’s interior remains smooth, If the blood vessel’s interior remains smooth, circulating blood does not clotcirculating blood does not clot If internal injury to the vessel occurs and a roughened If internal injury to the vessel occurs and a roughened

surface develops, intravascular clotting will take placesurface develops, intravascular clotting will take place Many factors required in the clotting process are Many factors required in the clotting process are

synthesized in the liversynthesized in the liver Prothrombin (II) and factors VII, IX, and X require Prothrombin (II) and factors VII, IX, and X require

vitamin K for synthesisvitamin K for synthesis Warfarin antagonizes vitamin K and interferes with Warfarin antagonizes vitamin K and interferes with

the synthesis of four clotting factors to produce an the synthesis of four clotting factors to produce an anticoagulant effectanticoagulant effect




Intravascular clots can form in certain Intravascular clots can form in certain diseasesdiseases Clots or thrombi may break off, forming emboliClots or thrombi may break off, forming emboli

that lodge in the smaller vessels of major organs that lodge in the smaller vessels of major organs such as the heart, brain, and lungssuch as the heart, brain, and lungs

Anticoagulant therapy attempts to reduce Anticoagulant therapy attempts to reduce intravascular clottingintravascular clotting If the dose is too large, hemorrhage may occurIf the dose is too large, hemorrhage may occur If the dose is too small, the danger of embolism If the dose is too small, the danger of embolism

remainsremains


WarfarinWarfarin(Coumadin)(Coumadin)

Haveles (pp. 208-209)Haveles (pp. 208-209) An oral anticoagulant that blocks the An oral anticoagulant that blocks the γγ--

carboxylation of glutamate residues in the carboxylation of glutamate residues in the synthesis of factors VII, IX, and X, prothrombin synthesis of factors VII, IX, and X, prothrombin (II), and endogenous anticoagulant protein C(II), and endogenous anticoagulant protein C Prevents the metabolism of the inactive vitamin K Prevents the metabolism of the inactive vitamin K

epoxide back to its active formepoxide back to its active form The pharmacologic effect is delayed when The pharmacologic effect is delayed when

therapy begins and endstherapy begins and ends



WarfarinWarfarin (Coumadin) (Coumadin)

Haveles (p. 208) (Fig. 15-9)Haveles (p. 208) (Fig. 15-9) Monitoring: the effect of warfarin is monitored Monitoring: the effect of warfarin is monitored

using the INRusing the INR A function of the prothrombin time (PT) of the A function of the prothrombin time (PT) of the

patient, PT of control, and the international patient, PT of control, and the international sensitivity index (ISI)sensitivity index (ISI)

The target INR for most indications is between 2 The target INR for most indications is between 2 and 3, it can range from 1 to 4and 3, it can range from 1 to 4



WarfarinWarfarin (Coumadin) (Coumadin)

Haveles (p. 208)Haveles (p. 208) Adverse reactions: the most common adverse Adverse reactions: the most common adverse

effects are various forms of bleedingeffects are various forms of bleeding Look for petechial hemorrhages on the hard palateLook for petechial hemorrhages on the hard palate Ecchymoses can occur, even without traumaEcchymoses can occur, even without trauma


Warfarin-Aspirin InteractionWarfarin-Aspirin Interaction

Haveles (p. 208) (Table 15-11)Haveles (p. 208) (Table 15-11) Patients taking warfarin should not be given Patients taking warfarin should not be given

aspirin or aspirin-containing products, aspirin or aspirin-containing products, bleeding episodes or fatal hemorrhages can bleeding episodes or fatal hemorrhages can resultresult Aspirin causes hypoprothrombinemia and alters Aspirin causes hypoprothrombinemia and alters

platelet adhesivenessplatelet adhesiveness• Can irritate the gastrointestinal tractCan irritate the gastrointestinal tract

Aspirin and warfarin compete for the same plasma Aspirin and warfarin compete for the same plasma protein-binding siteprotein-binding site• Increases the proportion of free (unbound) warfarin in the Increases the proportion of free (unbound) warfarin in the

bloodblood


Warfarin-Acetaminophen Warfarin-Acetaminophen InteractionInteraction

Haveles (p. 209)Haveles (p. 209) A statistically significant association was A statistically significant association was

found between acetaminophen use and the found between acetaminophen use and the abnormal elevation of the INRabnormal elevation of the INR Toxicity has not been proved Toxicity has not been proved


WarfarinWarfarin--Antibiotics InteractionAntibiotics Interaction

Haveles (p. 209) (Table 15-12)Haveles (p. 209) (Table 15-12) Antibiotics can potentiate the effect of warfarinAntibiotics can potentiate the effect of warfarin

Antibiotics reduce the bacterial flora in the GI tract Antibiotics reduce the bacterial flora in the GI tract that normally synthesize vitamin Kthat normally synthesize vitamin K

This results in a decrease in vitamin K absorbedThis results in a decrease in vitamin K absorbed Because warfarin also inhibits vitamin KBecause warfarin also inhibits vitamin K––dependent dependent

factors, an added anticoagulant effect occursfactors, an added anticoagulant effect occurs This interaction does not have a chance to This interaction does not have a chance to

develop when antibiotics are used before a develop when antibiotics are used before a dental proceduredental procedure


Management of the Dental Management of the Dental Patient Taking WarfarinPatient Taking Warfarin

Haveles (p. 209) (Box 15-9)Haveles (p. 209) (Box 15-9) Bleeding: consult with physician regarding PT Bleeding: consult with physician regarding PT

or INRor INR Analgesics: aspirin is contraindicated unless Analgesics: aspirin is contraindicated unless

the patient is taking one aspirin daily for its the patient is taking one aspirin daily for its anticoagulant effectanticoagulant effect


HeparinHeparin

Haveles (pp. 209-210)Haveles (pp. 209-210) One of the most commonly used One of the most commonly used

anticoagulant agents for hospitalized patients anticoagulant agents for hospitalized patients Administered by injection; not used orally Administered by injection; not used orally Used after MI, stroke (embolism), or Used after MI, stroke (embolism), or

thrombophlebitisthrombophlebitis When heparin is started, warfarin is also When heparin is started, warfarin is also

begunbegun An overdose of heparin is antagonized by An overdose of heparin is antagonized by

protamine sulfateprotamine sulfate


clopidogrelclopidogrel(Plavix)(Plavix)

Haveles (p. 210)Haveles (p. 210) An inhibitor of adenosine diphosphate (ADP)-An inhibitor of adenosine diphosphate (ADP)-

induced platelet aggregationinduced platelet aggregation Indicated for patients with recent history of MI or Indicated for patients with recent history of MI or

stroke, established peripheral arterial disease, and stroke, established peripheral arterial disease, and for patients with acute coronary artery syndromefor patients with acute coronary artery syndrome

Side effects include thrombotic thrombocytopenia Side effects include thrombotic thrombocytopenia purpura (TTP) and increased bleedingpurpura (TTP) and increased bleeding


ticlopidineticlopidine(Ticlid)(Ticlid)

Haveles (p. 211)Haveles (p. 211) An irreversible inhibitor of ADP-induced An irreversible inhibitor of ADP-induced

platelet aggregation, which results in platelet aggregation, which results in increased bleeding timeincreased bleeding time Indicated to decrease thrombotic stroke in patients Indicated to decrease thrombotic stroke in patients

with previous strokewith previous stroke Used in patients who are intolerant of aspirinUsed in patients who are intolerant of aspirin Major side effect is neutropeniaMajor side effect is neutropenia


streptokinase (Streptase, streptokinase (Streptase, Kabikinase) and alteplase (tPA, Kabikinase) and alteplase (tPA,

Activase) Activase) Haveles (p. 211)Haveles (p. 211)

Enzymes, called “clotbusters” are sometimes Enzymes, called “clotbusters” are sometimes used in the therapy of deep vein thrombosis, used in the therapy of deep vein thrombosis, arterial thrombosis, pulmonary embolism, and arterial thrombosis, pulmonary embolism, and acute coronary artery thrombosis associated acute coronary artery thrombosis associated with myocardial infarctionwith myocardial infarction Called Called thrombolytic drugsthrombolytic drugs because they promote because they promote

conversion of plasminogen to plasmin, the natural conversion of plasminogen to plasmin, the natural clot-resolving enzymeclot-resolving enzyme


dipyridamoledipyridamole(Persantine)(Persantine)

Haveles (p. 211)Haveles (p. 211) Used to prolong the life of platelets in patients Used to prolong the life of platelets in patients

with prosthetic heart valveswith prosthetic heart valves Artificial valves cause premature death of platelets Artificial valves cause premature death of platelets

due to their mechanical effect (trauma) on blood due to their mechanical effect (trauma) on blood cells passing through the valvescells passing through the valves


pentoxifyllinepentoxifylline(Trental)(Trental)

Haveles (p. 211) Haveles (p. 211) Improves blood flow by its hemorheologic Improves blood flow by its hemorheologic

effecteffect Lowers blood viscosity and improves flexibility of Lowers blood viscosity and improves flexibility of

red blood cellsred blood cells Indicated for claudication (limping) produced by Indicated for claudication (limping) produced by

chronic occlusive artery disease of the limbschronic occlusive artery disease of the limbs Side effects include cardiovascular and gastric Side effects include cardiovascular and gastric

symptomssymptoms


Drugs that Increase Blood Drugs that Increase Blood ClottingClotting

Haveles (p. 211)Haveles (p. 211) Hemostatic Agents (fibrinolytic inhibitors)Hemostatic Agents (fibrinolytic inhibitors)

Aminocaproic acid (EACA) and tranexamic acid Aminocaproic acid (EACA) and tranexamic acid (Cyklokapron) are similar to the amino acid lysine, (Cyklokapron) are similar to the amino acid lysine, and they inhibit plasminogen activationand they inhibit plasminogen activation

Adverse effects include intravascular thrombosis, Adverse effects include intravascular thrombosis, hypotension, and abdominal discomforthypotension, and abdominal discomfort• Used in the treatment of hemorrhage after surgeryUsed in the treatment of hemorrhage after surgery

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