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.