Calcium Channel Blockers

The agents commonly called the calcium channel blockers comprise an increasing number of agents, including the prototypical verapamil (Calan, Isoptin), nifedipine (Adalat, Procardia), and diltiazem (Cardizem). These agents are a chemically and pharmacologically heterogeneous group of synthetic drugs, but they possess the common property of selectively antagonizing Ca movements 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 vasodilating drugs, they lack the fluid-accumulating properties of other vasodilators and the persistent activation of the sympathetic and renin–angiotensin–aldosterone axes. Furthermore, the broad potential range of activities, both within and without the cardiovascular system, suggests that they may be clinically useful in disorders from vertigo to failure of gastrointestinal smooth muscle to relax . A number of second-generation analogues are known, particularly in the nifedipine (1,4-dihydropyridine) series, including nimodipine (Nimotop), nicardipine (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 exhibits very slow kinetics of onset and offset of blockade; and felodipine and nisoldipine are vascular-selective 1,4-dihydropyridines.