Calcium antagonists. Mechanisms, therapeutic indications and reservations: a review

The chief site of action of the calcium antagonist drugs is the slow calcium channel in two tissues: the atrioventricular node and vascular smooth muscle. The exact mode whereby these agents work is still unknown, but recently studies with radioligands suggest that the binding site for the dihydropyridines such as nifedipine is different from the site for the verapamil group (including diltiazem). In some way these agents 'close' or 'block' the calcium channels. Verapamil and diltiazem are active against the calcium channel of the atrioventricular node which nifedipine in clinical doses is not; in contrast, nifedipine is more active on peripheral vascular arterial muscle, presumably inhibiting the calcium channel more strongly. An intracellular site of action of these agents on calmodulin in vascular smooth muscle cannot be excluded. Clinically, the chief calcium antagonists (verapamil, nifedipine, diltiazem) constitute a powerful group of cardioactive agents with a spectrum of therapeutic actions rather similar to beta-adrenoceptor blockade, being effective in angina of effort and rest, and hypertension. Critical differences are dependent on the individual properties of the calcium antagonists. Thus only verapamil and diltiazem are effective in inhibiting the AV node while the dihydropyridines such as nifedipine are only vasodilators in clinical doses. As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed.