CHAPTER 8 ANTIHYPERTENSIVE DRUGS Classification 1. 2. 3. 4. 5. 6. 7. Diuretics. Beta adrenergic blockers. Calcium channel blockers.

Angiotensin converting enzyme inhibitors. Angiotensin receptor blockers. Sympatholytics and adrenergic blockers. Direct arterial vasodilators.

1.Diuretics Types
• • •

Thiazides and related diuretics. Loop diuretics. Potassium sparing diuretics.

Mechanism of Action
• •

Initial effects: through reduction of plasma volume and cardiac output. Long term effect: through decrease in total peripheral vascular resistance.

• • • •

Documented reduction in cardiovascular morbidity and mortality. Least expensive antihypertensive drugs. Best drug for treatment of systolic hypertension and for hypertension in the elderly. Can be combined with all other antihypertensive drugs to produce synergetic effect.

Side Effects

• •

Metabolic effects (uncommon with small doses): hypokalemia, hypomagnesemia, hyponatremia, hyperuricemia, dyslipidemia (increased total and LDL cholesterol), impaired glucose tolerance, and hypercalcemia (with thiazides). Postural hypotension. Impotence in up to 22% of patients.

Practical Considerations

Moderate salt restriction is the key for effective antihypertensive effect of diuretics and for protection from diuretic - induced hypokalaemia.

Renal impairment: loop diuretics. They are indicated with hypokalemia (serum potassium < 3. release of vasodilator prostaglandins. Potassium supplements should not be routinely combined with thiazide or loop diuretics.e. arrhythmias. Nonsteroidal antiinflammatory drugs can antagonize diuretics effectiveness. Frusemide needs frequent doses ( 2-3 /day ).• • • • Thiazides are not effective in patients with renal failure (serum creatinine > 2mg /dl) because of reduced glomerular filtration rate. Hypertension complicated with heart failure. heart block. Do not discontinue abruptly. Special Indications • • Diuretics should be the primary choice in all hypertensives. Other actions include decrease plasma renin activity. infarction.Adrenergic Blocking Agents Mechanisms of Action • • Initial decrease in cardiac output. death). Advantages • • • Documented reduction in cardiovascular morbidity and mortality. renal and obese hypertensives. Cardioprotection: primary and secondary prevention against coronary artery events (i.Thiazides can be given once daily or every other day. Relatively not expensive. They are indicated in: Volume dependent forms of hypertension: blacks. Preparations and Dosage: see table 12. Bradycardia . elderly. Side Effects • • Bronchospasm and obstructive airway disease. 2. Contraindicated in more than grade I AV. diabetic. resetting of baroreceptors.5 mEq/L) especially with concomitant digitalis therapy or left ventricular hypertrophy. Beta . ischemia. Practical Considerations • • • Beta blockers are used with caution in patients with bronchospasm. Resistant hypertension: loop diuretics in large doses are recommended. and blockade of prejunctional beta-receptors. followed by reduction in peripheral vascular resistance.

Maintain optimal physical. May improve renal function. Impotence. Special Indications • • • • • • Ischemic heart disease: when beta blockers are ineffective or contraindicated and in vasospastic angina. amlodipine. Hyperkinetic circulation and high cardiac output hypertension (e. Benzothiazepine: diltiazem. uric acid and lipids. Advantages • • • No metabolic distrubances: no change in blood glucose. headache. potassium.g. Non dihydropyridine : Phenylalkylamine: verapamil. Mask symptoms of hypoglycemia. Non dihydropyridine: aggravation of heart failure and heart block. Elderly hypertensives: second agent of choice after diuretics. Inhibition of aldosterone secretion. felodipine. - Mechanisms of action • • • Decrease in the concentration of free intracellular calcium ions results in decreased contraction and vasodilation. Hypertension associated with coronary artery disease. Peripheral vascular disease (e. young hypertensives). Calcium channel blockers Types • • Dihydropyridine: nifedipine. and sexual activities. lacidipine.. Preparations and Dosages: see table 12 3. nicardipine.g. Raynauld`s phenomenon). migraine. Fatigue. Practical Considerations . may worsen insulin sensitivity and cause glucose intolerance). Side Effects Dihydropyridine: flushing.• • • • • Metabolic effects (raise triglyerides levels and decrease HDL cholesterol. Increased incidence of diabetes mellitus.. essential tremors. Diuretic effect through increase in renal blood flow and glomerular filtration rate. Special Indications • • • • First line treatment for hypertension as an alternative to diuretics. or hypertrophic cardiomyopathy. Verapamil may cause constipation. Hypertension associated with supraventricular tachycardia. Coldness of extremities. mental. and lower limb oedema.

Favorable metabolic profile. Congestive heart failure. known allergy. Advantages • • • • • Reduction of cardiovascular morbidity and mortality in patients with atherosclerotic vascular disease. and potassium. A slight stable increase in serum creatinine after the introduction of ACE inhibitors does not limit use.Short acting dihydropyridine should be combined with beta blockers in coronary artery disease. ACE-I are more effective when combined with diuretics and moderate salt restriction. particularly with nephropathy.. help sodium excretion. and heart failure. 4. pregnancy.2%) : life threatening. Side Effects • • • • • • • Cough (10 . diabetes.30%): a dry irritant cough with tickling sensation in the throat. Angiotensin Converting Enzyme Inhibitors Types • • • Class I: captopril Class II (prodrug) : e. Postural hypotension in salt depleted or blood volume depleted patients. Practical Considerations • • • • Contraindications include bilateral renal artery stenosis. Improvement in glucose tolerance and insulin resistance. Angioedema (0. and hypertensive crisis. High serum creatinine (> 3 mg/dl) is an indication for careful monitoring of renal function. Decreased secretion of aldosterone.g. Peparations and Dosages: see table 12. and hyperkalaemia. Benefits can still be obtained in spite of renal insufficiency. enalapril. . and should be avoided in stroke. ramipril. Renal glomerular protection effect especially in diabetes mellitus. perindopril Class III ( water soluble) : lisinopril. Do not adversely affect quality of life. high risk with bilateral renal artery stenosis. Increased formation of bradykinin and vasodilatory prostaglandins. Special Indications • • • Diabetes mellitus.converting enzyme. Mechanism of Action • • • Inhibition of circulating and tissue angiotensin. Following myocardial infraction. Skin rash (6%). Renal failure: rare. Hyperkalaemia Teratogenicity.

doxazocin. Methyldopa: sedation.Preparations and dosages: see table 12. Advantages • • • Alpha1. 3.receptor blockers. and tolerance (due to fluid retention).aldosterone axis. Preparations and Dosages: see table 12. Alpha 1-receptor blockers: prazocin. 4. Prostatic hypertrophy: alpha 1. When there is a need for rapid reduction in blood pressure: clonidine. They do not produce cough. clonidine. imidazoline receptor agonists. moxonidine. Imidazoline receptor agonists: rilmenidine. Sympatholytics And Alpha Adrenergic Blockers Types 1. . Peripherally acting adrenergic antagonists: reserpine. Advantages • • • Similar metabolic profile to that of ACE-I.receptor blockers and imidazoline receptor agonists improve lipid profile and insulin sensitivity. Centrally acting alpha 2. hemolytic anemia. hepatotoxicity. Renal protection. Special indications: • • • • Diabetes mellitus: alpha1. Drug of choice during pregnancy. 6. Side Effects • • Prazocin: postural hypotension. Dyslipidemia: alpha 1. producing more blockade of the renin angiotensin . 5.receptor blockers.receptor blockers. imidazoline receptor agonists. and tolerance. diarrhea. occasional tachycardia.agonists: methyldopa. Methyldopa: increases renal blood flow. Angiotensin Receptor Blockers Mechanism of action They act by blocking type I angiotensin II receptors generally. Practical Indications Patients with a compelling indication for ACE-I and who can not tolerate them because of cough or allergic reactions. 2. Reserpine: neutral metabolic effects and cheap.

during the first year. Arrange follow-up visits at intervals no more than three months apart. weight loss. Clonidine: dry mouth. Consider adverse effects at initial prescription and follow up visits. inability to read instructions. Practical Considerations • • Prazocin. diazoxide. Prescribe simple once-daily regimens. Patients’ compliance to antihypertensive medications Poor adherence to antihypertensive therapy remains a major therapeutic challenge contributing to the lack of adequate control of blood pressure in more than two thirds of patients with hypertension. and minoxidil (see chapter 10). Adverse drug effects. One half of all patients discontinue antihypertensive medications within one year. complicated multidose regimens. methyldopa. sedation.g.• • Reserpine: depression. Strategies to Improve Compliance • • • • • • • • Educate patients about the disease and involve their families in the treatment. Very long intervals between follow-up visits. etc…. nitroprusside. Logistic barriers e. and frequent change of doctors impair the doctor-patient relationship. 7. and reserpine should be combined with a diuretic because of fluid retention. lethargy. Causes of Poor Compliance • • • • Hypertension has no symptoms and treatment has to continue indefinitely. reserpine is only available as combination pill with thiazide (Brenardine) which contains 0. Poor communication with the patient. Stress that treatment is life-long. Consider cost while prescribing. Direct Arterial Vasodilators Types: hydralazine. bradycardia. impotence. . Allow extra visits for blood pressure measurement at no extra charge to the patient. In Egypt. diarrhea. Encourage life style modifications. expense of medications. and impotence. and rebound hypertension if stopped suddenly. peptic ulcer. Preparations and Dosages: see table 12.1 mg of reserpine per tablet.

5-10 2-4 (or more ) 50-150 ACE inhibitors Enalapril 2. 160 160 Hydrochlorothiazide12.10.10 5 240 120 60 60 90. 100 50 100 5.25-5 25-50 20-400 1-4 ( or more ) 25-100 Metoprolol Bisoprolol 50-200 2.4 25.20 20 1. 10 5 2. 10 5 2.Table 12.5.20 5. 50 50 25.5 1.5-40 Lisinopril Ramipril 10-40 2.25.5-20 Perindopril Angiotensin Receptor blockers Losartan 2-8 25-100 Valsartan 80-320 .4 50 50 50 100 80.5-10 Calcium antagonists Verapamil Diltiazem 120-480 90-240 Nifedipine Amlodipine Lacidipine Captopril 20-80 2. 160 80. 5. 180 20 20 5. 50 10. 2. 100 50.5-50 Indapamide Chlorthalidone Frusemide Bumetanide Beta adrenergic blockers Atenolol 1. 120.20 10.5 50 40 1 50.5 2. Commonly Used Oral Antihypertensive Medications Class Diuretics Generic Name Daily Dose (mg) Common Brand Name(s) Hydrex Aldactazide # Moduretic ++ Natrilix Natrilix SR Hygrotone Lasix Burinex Tenormin Blockium Blockium Diu * Betaloc Concor Concor 5 Plus* Isoptin retard Tarka *** Tildium Altiazem Delaytiazem Adalat retard Epilat retard Norvasc Amilo Lacipil Capoten Capozide * Captopril Renetec Co-renetec Ezapril Zestril Zestoretic Tritace Tritace comp * Tritace comp LS * Coversyl Cozaar Hyzaar * Losartan Fortzar* Tareg Co-Tareg * Co-Diovan* Tablet Size (mg) 25 25 25 2. 20 10.

1 * Combination with hydrochlorothiazide with ACE inhibitor with spironolactone ++ Combination with triametrene *** Combination ** Combination with thiazide & vasodilator . 500 0.Candesartan Telmisartan Alpha-adrenergic blockers Prazocin Doxazocin Centrally acting drugs Methyldopa Clonidine Rilmenidine Reserpine 4-32 20-80 1-16 1-16 500-2000 0.1-1. 0.2 1-2 0. 80 1.4 250.0 0.1 # Combination Atacand Micardis Minipress Cardura Aldomet Catapres Rilmenidine Brenardine 8 40. 0.1.3 1.2.2 1.

Sign up to vote on this title
UsefulNot useful