Pharmacologic importance of the combination atenolol/nifedipine in hypertensive patients

Abstract

When used as first-line treatment, any monotherapy selected from one of the main classes of agents for the management of slight to moderate arterial hypertension cannot be expected to have a success rate exceeding 60%. However, this level of efficacy approaches 80% if two classes of antihypertensive drugs with complementary modes of action are combined--a notable example being the combination of a beta-blocker, atenolol 50 mg, and a calcium antagonist, sustained-release nifedipine 20 mg. This fixed combination provides efficacy and tolerability in the treatment of arterial hypertension. Atenolol has beta-adrenolytic properties similar to those of propranolol, the most commonly named comparator drug. Atenolol is a selective beta 1-adrenergic antagonist with negative chronotropic, bathmotropic, dromotropic and inotropic actions. Because of its selectivity, it induces only moderate vasoconstriction. Its cardioselective nature diminishes the risk of bronchospasm, an event commonly induced by this type of drug. Atenolol reduces renin secretion from the renin-angiotensin system and consequently decreases the production of angiotensin II and plasma aldosterone. The renal effects of atenolol are an increase in both diuresis and natriuresis, with a reduction in the renal plasma flow. beta-Adrenergic antagonists in general modify carbohydrate metabolism and may mask the precursor signs of hypoglycaemia. They have a negligible effect upon lipid metabolism and practically no effect on total or high density lipoprotein cholesterol levels. Nifedipine belongs to the class of dihydropyridines. It acts by blocking the influx of calcium ions through the slow channels. Although a potent vasodilating agent, nifedipine does not induce tachycardia or water-sodium retention. The negative inotropic effect observed in vitro has not been reported in humans; the coronary dilatation produced by nifedipine is indisputable, both in unstable angina and exertional or exercise-induced angina. However, its cardioprotective effect remains questionable outside the context of recent-onset atheromatous plaques. Nifedipine increases renal blood flow and is practically devoid of diabetes-inducing factors. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg offers a particularly interesting complementary action, the beta-blocker reducing the dihydropyridine-induced activation of the sympathetic nervous system and the latter reducing the vasoconstriction induced by the beta-blocker. Compared with each agent used alone, the pharmacokinetic profiles of atenolol and nifedipine remain unmodified by their administration in the fixed combination.