Development and trends in the drug treatment of essential hypertension.

AIM

A brief survey is given of the development of the drug therapy of essential hypertension over five decades, followed by a discussion on newer antihypertensive drugs and principles.

DRUGS THAT MODULATE THE SYMPATHETIC NERVOUS SYSTEM

Virtually all levels and elements of the sympathetic nervous system can be modulated by drugs in such a manner that elevated blood pressure is lowered, for instance with the use of central alpha 2-adrenoceptor agonists (clonidine, alpha-methyldopa), ganglioplegic drugs, peripheral adrenergic neurone blockers, and alpha- and beta-adrenoceptor antagonists. The beta-blockers have been maintained as a very major group of antihypertensive therapeutics. Among alpha-adrenoceptor antagonists, only the selective alpha 1-blockers are useful as antihypertensive drugs, although some interest has developed in newer alpha 2-adrenoceptor antagonists which are selective for postsynaptic alpha 2-adrenoceptors.

DIURETICS

Diuretics, in spite of some criticism, are still a cornerstone in antihypertensive drug treatment. Their position has been reinforced by the results of the recent Systolic Hypertension in the Elderly Program, Swedish Trial in Old Patients with Hypertension and Medical Research Council (Elderly) trials.

CALCIUM ANTAGONISTS

Calcium antagonists have been extended by several new dihydropyridines which appear to be more vasoselective than the classical compounds.

ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS: Various new ACE inhibitors have been introduced, but so far they have not clearly offered major advantages over the established compounds.

NEW POTENTIAL ANTIHYPERTENSIVE DRUGS

Renin inhibitors and angiotensin II-receptor antagonists are being studied for their potential as antihypertensive drugs and they are also important because they may modulate the renin-angiotensin-aldosterone system. Inhibitors of neutral endopeptidase will cause an accumulation of endogenous atrial natriuretic peptide, and hence lower blood pressure by counteracting several effects of the renin-angiotensin-system. Potassium channel openers are vasodilators and potential antihypertensive drugs with additional anti-ischaemic activity.