A Review of Antihypertensive Therapy Novel compounds are appearing and concepts are changing

Over the past decade a simple stepped-care approach to the treatment of hypertension has been developed. However, new therapeutic concepts and development of antihypertensive agents with novel modes of action means that these stepped-care guidelines are continually being revised.

Lower doses of diuretics are being used in the USA and, while the link between diuretic-induced hypokalaemia and cardiac dysrhythmias remains controversial, sodium intake can be limited to increase the effectiveness of the diuretic and reduce the incidence of hypokalaemia. Further, amiloride, indapamide and bumetanide have been introduced to the US market. Amiloride is potassium-sparing and natriuretic, bumetanide is a 'loop-acting' diuretic and the action of indapamide is similar to that of the thiazides. Amiloride should not be given with potassium supplements or to patients with compromised renal function. However, patients with congestive heart failure or impaired renal function can receive bumetanide if unresponsive to thiazide diuretics. ,8-Biockers are established antihypertensive agents and, although the mechanism by which they reduce BP is not entirely clear, the choice of a suitable agent may be influenced by their cardioselectivity, lipid solubility, intrinsic sympathomimetic activity and membrane stabilising activity. Pindolol, and possibly acebutolol, have intrinsic sympathomimetic activity and can be used in patients with reduced cardiac output or bradycardia. Further. cardioselective agents such as metoprolol and atenolol are more suitable for asthmatics but, in doses used for hypertension, they may still block ,82-receptors.

Antiadrenergic drugs can act either centrally (clonidine, methyldopa, guanabenz and guanfacine), peripherally (prazosin and trimazosin), or by both mechanisms (urapidil) to treat hypertension. Further, by competitive inhibition of serotonin receptors on the arteriolar smooth muscle, ketanserin achieves the same haemodynamic effects as prazosin and may be an effective treatment for essential hypertension. Calcium antagonists have also been developed and, although these drugs produce arteriolar dilatation and reduce total peripheral resistance, they do not appear to cause the fluid retention observed with 'traditional' vasodilators. Nifedipine, for example, causes unexplainable pedal oedema but its natriuretic activity means that it can be given without a diuretic. Finally, angiotensin-converting enzyme inhibitors such as captopril and enalapril reduce BP by modifying the formation of the potent vasconstrictor angiotensin and, in the future, inhibitors which act at other levels in the renin-angiotensin system may have important clinical implications in the treatment of hypertension. Frohlich ED Cardiology 72 349·365, Sep-Dec 1985

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