ANTIHYPERTENSIVE AGENTS

ANTIHYPERTENSIVE AGENTS are used to reduce high blood pressure when it is raised in disease, though such drugs are not necessarily hypotensive (i.e. they may not lower blood pressure in normotensive subjects). Hypertension is an elevation of arterial blood pressure above the normal range expected in a particular age group, sex etc. It can have several different causes, which to some extent determine the treatment. Above certain values, after making lifestyle corrections, intervention with drug therapy may reduce the risk of heart attacks, kidney failure or a stroke, and may help in the treatment of angina pectoris. There are several large groups of drugs used as antihypertensives, each with a specific mode of action.

DIURETICS are in common use as antihypertensives, and often a mild diuretic may be all that is required: e.g. amiloride. chtorothiazide, ethacrynic acid, frusemide, hydrochlorothiazide, spironolactone, triamterene.

Beta-blockers, of which there are many, may be used if further treatment is necessary, with or without simultaneous administration of a diuretic: e.g. acebutolol, oxprenolol, propranolol and sotalol. See β-ADRENOCEPTOR ANTAGONISTS.

Other antihypertensive drugs work as antisympathetic agents to reduce sympathetic nervous systems activity, though the a-blockers are now little used because of adverse side-effects: e.g. indoramin. See β-ADRENOCEPTOR ANTAGONISTS. Antisympathetic agents effecting blood pressure control in the brain are also used (e.g. methyldopa), as do adrenergic neuron blocking drugs (e.g. debrisoquine).

VASODILATORS are commonly used in hypertensive treatment, and these direct-acting agents may work via a number of different mechanisms. The CALCIUM-CHANNEL BLOCKERS (e.g. amlopidine, isradipine, nicardipine, nifedipine, verapamil) are increasingly used. Some new types of vasodilators act by opening potassium channels in the smooth muscle cell membrane: e.g. nicorandil. See POTASSIUM-CHANNEL ACTIVATORS. Although the nitrates and nitrites have a profound vasodilator action, they are reserved for acute hypertensive crisis (e.g. sodium nitroprusside) or for the treatment of angina (e.g. glyceryl trinitrate). Hydralazine has acute and long-term uses as a vasodilator: its mode of action is poorly understood. ACE INHIBITORS are now widely used for certain types of hypertension: e.g. captopril. enalapril, lisinopril, quinapril, ramipril. Antagonists acting at angiotensin AT1 receptors (e.g. losartan) have recently been introduced for the treatment of hypertension and show promise. See ANGIOTENSIN RECEPTOR ANTAGONISTS.