DIURETICS- CORNERSTONE OF ANTIHYPERTENSIVE THERAPY

The mechanisms by which diuretics lower blood pressure are not thoroughly understood, but strong evidence exists for the role of persistent reduction in total body sodium and plasma volume. Mild to moderate hypertension is often controlled with a diuretic alone. In cases of more severe hypertension, diuretics can enhance the effects of other types of antihypertensives, many of which can cause salt and water retention. Diuretic therapy is generally well tolerated; Polyuria usually lasts only days or a few weeks in non-oedematous patients. Unlike other antihypertensives, diuretics do not produce significant postural hypotension.

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Selecting a diuretic In discussing the various diuretic agents available, it is helpful to consider them in 3 groups, based on their site of action. Group I, the 'loop diuretics', includes frusemide (furosemide) and ethacrynic acid. Group II agents act on the cortical diluting segment and include chlorothiazide, its congeners and the non-thiazide compounds chlorthalidone and metolazone. Group III agents, e.g. spironolactone, triamterene and amiloride, act on the distal tubule and collecting duct. In regard to antihypertensive activity, Group I and Group II agents have about equivalent effects. However, the greater diuretic

activity of the Group I diuretic agents increases the risk of severe volume depletion, hypokalaemia and metabolic acidosis when these diuretics are used. Hence, these agents should be reserved for use:

• in hypertensive patients with congestive heart failure whose extracellular fluid volume cannot be adequately controlled with less potent diuretics

• in hypertensive emergencies - intravenous loop diuretics can counteract the strong sodium retaining effects of intravenous vasodilators

• in cases in which large doses of drugs such as methyldopa, hydrallazine or minoxidil, are used, resulting in sodium retention.

• in hypertensive patients with renal insufficiency

Group III diuretics have been useful in patients treated with Group I or II diuretics who develop secondary sodium retention and a rise in blood pressure subsequent to an increase in aldosterone secretion. Group III diuretics can be given to counteract the kaliuretic effects of other diuretics.

'However, the commercially available combinations of a thiazide and spironolactone or triamterene do not reliably !1'.aintain the seru.m potassium within the normai range, and serum potassium should be determined frequently when any diuretic regimen is initiated. '

Recently, spironolactone has been employed in the diagnosis and management of hypertension associated with primary hyperaldosteronism and low plasma renin activity.

Side-effects to consider All diuretics in Groups I and II may induce hypokalaemia, metabolic alkalosis and hyperuricaemia. Carbohydrate intolerance may develop in some patients. Ethacrynic acid and frusemide can cause reversible (and possibly irreversible?) hearing loss when administered in high doses. Spironolactone and triamterene may produce hyperkalaemia, especially in patients with renal insufficiency. Spironolactone may cause decreased libido, gynaecomastia and impotence in the male, and it may cause menstrual irregularities and breast enlargement in the female. ( 45 references)

Page, L.B. et al.: American Heart Journal91: 810-815 (Jun 1976)

INPHARMA 16th June,1976 p17