Calcium Antagonists. Mechanisms, Therapeutic Indications and Reservations: A Review

The chief site of action of the calcium antagonist drugs isthe slow calcium channel in two tissues: the atrioventricularnode and vascular smooth muscle. The exact mode whereby theseagents work is still unknown, but recently studies withradioligandssuggest that the binding site for the dihydropyridines suchas nifedipine is different from the site for theverapamil group(including diltiazem). In some way these agents ‘close’or ‘block’ the calcium channels. Verapamil and diltiazemare active against the calcium channel of the atrioventricularnode 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. Anintracellular site of action of these agents on calmodulin invascular smooth muscle cannot be excluded. Clinically, the chiefcalcium antagonists (verapamil, nifedipine, diltiazem) constitutea powerful group of cardioactive agents with a spectrum of therapeuticactions rather similar to beta-adrenoceptor blockade, beingeffectivein angina of effort and rest, and hypertension. Critical differencesare dependent on the individual propertiesof the calcium antagonists.Thus only verapamil and diltiazem are effective in inhibitingthe AV node while the dihydropyridines such as nifedipine areonly vasodilators in clinical doses. As a group, calcium antagonistscause vascular dilation and do not cause bronchial constriction,in contrast to the beta-adrenoceptor blocking agents. In manypatients these diverse properties allow safe combination ofcalcium antagonists and beta-adrenoceptor blockers if due careis observed.