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Antihypertensive Agents

Hypertension is the most common cardiovascular disease Hypertension is the most common cardiovascular disease. It can be classified into: I- Essential or primary hypertension: The cause for rise in blood pressure is not known. Responsible for majority of cases. II- Secondary hypertension: where rise is due to renal disease (diffuse glomerulonephritis, pyelonephritis), some vascular diseases (renal artery disease) or some endocrinal disorders (pheochromocytoma, Cushing’s syndrome and primary aldosteronism).

Systemic arterial blood pressure is determined by cardiac output and total peripheral resistance. In most of the cases, rise in BP is due to increase in total peripheral resistance. The blood pressure is mainly controlled by two systems. Firstly through the baroreceptors and the adrenergic nervous system. Secondly through renin angiotensin system, which is involved in the pathogenesis of some forms of secondary hypertension.

Clinically, hypertension can be divided into mild, moderate and severe Clinically, hypertension can be divided into mild, moderate and severe. The diastolic blood pressure between 90-104 mmHg is graded as mild hypertension, 105-114 mmHg is moderate and above 115 mmHg is severe. The person having systolic blood pressure more than 160 mmHg with low diastolic blood pressure is termed as ‘isolated systolic hypertension’ commonly seen in elderly person.

Classification of antihypertensive agents Centrally acting sympathetic inhibitors: Clonidine, methyldopa. II. Adrenergic neurone blocking agents: Reserpine, guanethidine. III. Adrenergic receptor antagonists: i. Alpha blockers: Prazosin, terazosin, doxazosin, phentolamine. ii. Beta blockers: Propranolol, metoprolol, atenolol, sotalol, pindolol. iii. Alpha & beta blockers Carvedilol: Labetalol.

IV. Angiotensin converting enzyme (ACE) inhibitors: Captopril, enalapril, benzapril. V. Angiotensin II receptor (type AT1) antagonist: Losartan, irbesartan. VI. Calcium channel blockers: Verapamil, diltiazem, nifedipine. Direct vasodilators VIII. Diuretics

Clonidine It stimulates presynaptic α2 receptors in vasomotor center of brain causing decreased sympathetic outflow. Adverse effects; drowsiness, dry mouth, restlessness, anxiety, nightmares, dizziness, skin rash, constipation and impotence. Reserpine It is an alkaloid obtained from the roots of ‘Rauwolfia Serpentina’. It is known to deplete adrenaline, noradrenaline, dopamine and 5-HT. CNS side effects, lethargy, apathy, psychic depression which may result in suicidal tendancy. Endocrinal disturbances include gynecomastia and impotence. It is not used now clinically.

Prazosin It selectively blocks post synaptic α1 receptors. Adverse effects include postural hypotension, dizziness, tachycardia, palpitation, headache, weight gain, nasal stuffiness, priapism and skin rash. Propranolol It is blocks β1, β2 decreasing HR and force of cardiac contraction. The renin secretion is inhibited. Adverse effects are skin rash, depression, nightmares, sexual dysfunction, epigastric distress, cold extremities and hypoglycaemia. Labetalol It is a mixed antagonist (α1 and non-selective β-receptor antagonist). It is more potent in blocking β than α receptors. It is potent hypotensive agent especially useful in pheochromocytoma.

CAPTOPRIL ACE inhibitors inhibit the conversion of angiotensin I (inactive) to angiotensin II (active) by inhibiting angiotensin converting enzyme. Decrease in Ag II results in vasodilation and decreased aldosterone secretion. They can be given safely in patients with diabetes or bronchial asthma. They are efficacious and well tolerated. They are also useful in coronary artery diseases as they reduce cardiovascular morbidity and mortality by improving coronary perfusion. ACE inhibitors are now first line drug in all grades of hypertension and can be safely used with diuretics and β blockers. Side effects include dry cough, skin rash, loss of taste, hyperkalemia, vertigo, vomiting, fatigue, neutropenia (rare), proteinuria and anemia.

LOSARTAN Angiotensin II is a potent vasoconstrictor, stimulant of aldosterone secretion. Both losartan and its principal active carboxylic acid metabolite, EXP3174 (10-40 times more potent than losartan) block the effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor. Adverse effects seen most often are dizziness and rash. Angioedema (swelling of face, lips and/or tongue) have been rarely reported. There is also headache, asthenia and fatigue.