Pharmacological aspects of calcium channel blockers

Summary

Calcium channel blockers (CCBs) inhibit voltagedependent L-type calcium channels. This leads to vascular smooth muscle relaxation and negative inotropic and chronotropic effects in the heart. The latter are counteracted in vivo by a vasodilatation-triggered, baroreceptor-mediated reflex increase in sympathetic tone, resulting in indirect cardiostimulation. The mean vascular/cardiac effect ratios of the first-generation CCBs—verapamil, nifedipine, and diltiazem—are relatively low and amount to approximately 3, 10, and 3, respectively. The pharmacokinetic properties of verapamil, nifedipine, and diltiazem are similar. The drugs are almost completely absorbed after oral administration, but their bioavailability is reduced because of first-pass hepatic metabolism. The onset of action of verapamil, nifedipine, and diltiazem, at least in immediate-release formulations, is relatively fast (0.5–2 hours), and their elimination half-lives range from 2 to 7 hours. The second-generation CCBs (e.g., amlodipine, felodipine, and nisoldipine) have a slower onset of action (due to either intrinsic properties of the drug or a slow-release formulation), a longer duration of action, and greater vascular/cardiac effect ratios. These features may provide therapeutic benefits, for example, a less pronounced increase in sympathetic tone and reflex tachycardia, and reduced likelihood of negative inotropic effects. These agents can therefore probably be used in patients with left ventricular dysfunction.