HYPERTENSIONPrinciple of Drug Therapy

Mohammad Ilyas, M.D.

Assistant Clinical Professor

University of Florida / Health Sciences Center

Jacksonville, Florida USA

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Why Treat HTN?

All Symptomatic patients, treatment is Mandatory:

Damage to the vascular epithelium, paving the path for

atherosclerosis (IHD, CVA) or nephropathy due to high

intra-glomerular pressure

Reduction of the blood pressure by 5 mmHg can

decrease the risk of stroke by 34%, of ischaemic heart

disease by 21%.

Hypertension, even asymptomatic needs treatment

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Types of

Hypertension

Essential Secondary

A disorder of unknown origin affecting the

Blood Pressure regulating mechanismsSecondary to other disease processes

Environmental

Factors

Stress Na+ Intake Obesity Smoking

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Risk factors for CVD

1. Age above 55 and 65 in Men and Woman respectively

2. Family History

3. Smoking

4. DM and Dyslipidemia

5. Hypertension

6. Obesity

7. Microalbuminuria

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JNC 7 (2003) Hypertension Classification and Management

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JAMA. 2013;():. doi:10.1001/jama.2013.284427

JNC 8 (2014 Hypertension Guideline Management Algorithm)

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JAMA. 2013;():. doi:10.1001/jama.2013.284427

JNC 8 (2014 Hypertension Guideline Management Algorithm)

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Blood Pressure Regulation

Blood Pressure = Cardiac output (CO) X Resistance to passage of blood through pre-capillary arterioles (PVR)

Physiologically CO and PVR is maintained minute to minute by –arterioles (1) post-capillary venules (2) and Heart (3)

Kidney is the fourth site – volume of intravascular fluid

Baroreflex, humoral mechanism and renin-angiotensin-aldosterone system regulates the above 4 sites

Local agents like Nitric oxide

In hypertensives – Baroreflex and renal blood-volume control system – set at higher level

All antihypertensives act via interfering with normal mechanisms

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Baroreceptor reflex arc

Postural baroreflex:

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The Renal response

Long-term blood pressure control – by controlling blood volume

Reduction in renal pressure - intrarenal redistribution of pressure and increased absorption of salt and water

Decreased pressure in renal arterioles and sympathetic activity –renin production – angiotensin II production

Angiotensin II:

Causes direct constriction of renal arterioles

Stimulation of aldosterone synthesis – sodium absorption and increase in intravascular blood volume

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Start one drug, titrate to maximum dose, and then add a second drug

Start one drug and then add a second drug before achieving maximum dose of the initial drug

Begin with 2 drugs at the same time, either as 2 separate pills or as a single pill combination

Strategies to Dose of Antihypertensive Drugs13

Principle of Pharmacologic Therapy

Initial mono-therapy in uncomplicated hypertension

Thiazide diuretics, long-acting calcium channel blockers and ACE

inhibitors or angiotensin II receptor blockers.

Beta blockers are not commonly used for initial mono therapy in

the absence of a specific indication

Combination therapy - with drugs from different classes

has a substantially greater blood pressure lowering effect

than doubling the dose of a single agent.

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Pre-hypertension

Individuals who are pre-hypertensive are not candidates for drug therapy but

Should be firmly and unambiguously advised to practice lifestyle modification

Those with pre-HTN, who also have diabetes or kidney disease, drug therapy is indicated if a trial of lifestyle modification fails to reduce their BP to 130/80 mmHg or less.

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Isolated Systolic Hypertension

Not distinguished as a separate entity as far as management is concerned.

SBP should be primarily considered during treatment and not just diastolic BP.

Systolic BP is more important cardiovascular risk factor after age 50.

Diastolic BP is more important before age 50.

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Frequency Distribution of Untreated HTN by Age17

Isolated Systolic

HTN

Isolated Diastolic

HTN

Systolic Diastolic

HTN

Treatment of Hypertension

7 compelling Indications:

Heart failure

Coronary artery disease

H/o MI

H/o stroke

Diabetes

Chronic Renal failure

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You must know

Classification of Antihypertensive

Antihypertensive mechanisms:

Diuretics, ACE inhibitors, ARBs, Beta-blockers, alpha-blockers,

CCBs, Vasodilators and central sympatholytics

Pateint status of Drugs

Preparation and dosage of commonly used drugs.

Common Adverse effects of Drugs

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General principles

Stage I:

Start with a single most appropriate drug with a low dose.

Preferably start with Thiazides. Others like beta-blockers, CCBs, ARBs and ACE inhibitors may also be considered. CCB – in case of elderly and stroke prevention. If required increase the dose moderately

Partial response or no response – add from another group of drug, but remember it should be a low dose combination

If not controlled – change to another low dose combination

In case of side effects lower the dose or substitute with other group

Stage 2: Start with 2 drug combination – one should be diuretic

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Combination therapy

In clinical practice a large number of patients require combination therapy – the combination should be rational and from different patterns of haemodynamic effects

Sympathetic inhibitors (not beta-blockers) and vasodilators + diuretics

Diuretics, CCBs, ACE inhibitors and vasodilators + beta blockers (blocks renin release)

Hydralazine and CCBs + beta-blockers (tachycardia countered)

ACE inhibitors + diuretics

3 (three) Drug combinations: CCB+ACE/ARB+diuretic; CCB+Beta blocker+ diuretic; ACEI/ARB+ beta blocker+diuretic

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Principle of Combination

Never combine:

Alpha or beta blocker and clonidine - antagonism

Nifedepine and diuretic synergism

Hydralazine with prazosin

Diltiazem and verapamil with beta blocker – bradycardia

Methyldopa and clonidine

Hypertension and pregnancy:

No drug is safe in pregnancy

Avoid diuretics, propranolol, ACE inhibitors, Sodium nitroprusside etc

Safer drugs: Hydralazine, Methyldopa, cardioselective beta blockers and prazosin

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Nocturnal therapy

The average nocturnal blood pressure is approximately 15

percent lower than daytime values.

Failure of the blood pressure to fall by at least 10 percent

during sleep is called "non-dipping," and is a stronger

predictor of adverse cardiovascular outcomes than daytime

blood pressure.

Shifting at least one antihypertensive medication from the

morning to the evening both may restore the normal

nocturnal blood pressure dip, and reduces 24-hour mean

blood pressure.

Nocturnal antihypertensive therapy may reduce the

incidence of cardiovascular disease

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Resistant hypertension

Resistance is usually defined as a diastolic blood pressure

above 90 mmHg despite intake of three or more

antihypertensive medications including a diuretic.

Suboptimal therapy

Extracellular volume expansion

Poor compliance with medical or dietary therapy

Identifiable or secondary hypertension

Office or "white coat" hypertension

Ingestion of substances that can elevate the blood

pressure

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Individualizing antihypertensive therapy

Indication Antihypertensive drugs

Systolic heart failureACE inhibitor or ARB, beta blocker, diuretic, aldosterone antagonist*

Post-myocardial infarctionACE inhibitor, beta blocker,

ARB, aldosterone antagonist

Proteinuric kidney disease ACE inhibitor and/or ARB

Angina pectorisBeta blocker, calcium channel

blocker

Atrial fibrillation rate control Beta blocker, non-dihydropyridinecalcium channel blocker

Atrial flutter rate control Beta blocker, non-dihydropyridine

calcium channel blocker

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Individualizing antihypertensive therapy

Benign prostatic hyperplasia Alpha blocker

Essential tremorBeta blocker

(noncardioselective)

Hyperthyroidism Beta blocker

MigraineBeta blocker, calcium

channel blocker

Osteoporosis Thiazide diuretic

Raynaud's syndromeDihydropyridine calcium

channel blocker

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Contraindications

Angioedema ACE inhibitor

Bronchospastic disease Beta blocker

Depression Reserpine

Liver disease Methyldopa

Pregnancy (or at risk for) ACE inhibitor, ARB, renin inhibitor

Second or third degree heart

block

Beta blocker, non-

dihydropyridine calcium channel

blocker

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Adverse effect

Depression Beta blocker, central alpha-2 agonist

Gout Diuretic

HyperkalemiaAldosterone antagonist, ACE inhibitor,

ARB, renin inhibitor

Hyponatremia Thiazide diuretic

Renovascular disease ACE inhibitor, ARB, or renin inhibitor

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Discontinuing therapy

If the BP is well control on monotherapy

55 % of patients remain normotensive for at least one to two years

More gradual tapering of drug dose is indicated in well-controlled

patients taking multiple drugs

Abrupt cessation of therapy with a short-acting beta-blocker (such

as propranolol) or the short-acting alpha-2-agonist clonidine can

lead to a potentially fatal withdrawal syndrome.

Gradual discontinuation of these agents over a period of weeks

should prevent this problem.

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Pearls

The only thiazide that will work with an elevated creatinine is metolazone (zaroxolyn)

If creatinine is elevated than use a loop diuretic

If potassium is elevated, evaluate current meds and use a diuretic

If potassium is low – ask why

If edema present – and ask why

Elderly patients benefit from blood pressure management

Black patients benefit from ACE/ARB – may need to use larger doses to obtain BP lowering effect

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Pearls Cont.

Metabolic acidosis and hyperkalemai?

Take blood pressure periodically lying and

standing so as not to miss supine (orthostatic)

hypertension associated with autonomic

insufficiency – this is treated differently

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Treatment failure – Why ?

“Drugs don’t work in patients who

don’t take them”

C. Everett Koop, MD, Former US Surgeon General

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Medication Use Continuum33

Osterberg, L. et al. N Engl J Med 2005;353:487-497

Adherence to Medication According to Frequency of Doses

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