Calcium Channel Blockers

Calcium Channel Blockers

The agents commonly called the calcium channel blockers comprise an increasing number of agents, includ-ing the prototypical verapamil (Calan, Isoptin), nifedipine (Adalat, Procardia), and diltiazem (Cardizem). These agents are a chemically and pharmacologically heteroge-neous group of synthetic drugs, but they possess the com-mon property of selectively antagonizing Ca⁺⁺ move-ments that underlie the process of excitation–contraction coupling in the cardiovascular system. The primary use of these agents is in the treatment of angina, selected cardiac arrhythmias, and hypertension.

Although the Ca⁺⁺ channel blockers are potent va-sodilating drugs, they lack the fluid-accumulating prop-erties of other vasodilators and the persistent activation of the sympathetic and renin–angiotensin–aldosterone axes. Furthermore, the broad potential range of activi-ties, both within and without the cardiovascular system, suggests that they may be clinically useful in disorders from vertigo to failure of gastrointestinal smooth mus-cle to relax .

A number of second-generation analogues are known, particularly in the nifedipine (1,4-dihydropyri-dine) series, including nimodipine (Nimotop), nicardip- ine (Cardene), felodipine (Plendil), nisoldipine (Sular), and amlodipine (Norvasc). These agents differ from nifedipine principally in their potency, pharmacokinetic characteristics, and selectivity of action. Nimodipine has selectivity for the cerebral vasculature; amlodipine ex-hibits very slow kinetics of onset and offset of blockade; and felodipine and nisoldipine are vascular-selective 1,4-dihydropyridines.