Calcium channel blockers (CCBs) inhibit voltage-dependent 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.