Calcium channel antagonists in the treatment of coronary artery disease: fundamental pharmacological properties relevant to clinical use.

Calcium channel antagonists are a diverse group of drugs with clinical antianginal and antihypertensive properties. They have as a common property the capacity to lessen the rate of calcium ion entry through a specific type of calcium channel, namely the voltage-gated L-type channel. They do not bind to all the pore molecules; therefore, there is still some residual entry of calcium ions. Variables determining the clinical efficacy of the different drugs include the binding sites involved, the tissue specificity of the drug, the duration of action, and (closely related) the degree of counter-regulatory neurohumoral activation. Inhibitory effects on the calcium channels of vascular smooth muscle explain the antihypertensive effect and the reduction of afterload, one of the antianginal mechanisms common to all of the drugs. In general, the dihydropyridines, such as nifedipine, are more vascular-selective than the non-dihydropyridines, such as verapamil and diltiazem. The latter owe part of their antianginal activity to more prominent effects on the calcium channels in the sinoatrial node (decreased heart rate) and the myocardium (negative inotropic effect). In addition, calcium channel antagonists are coronary artery vasodilators. Whether the latter effect confers on these drugs any specific advantage in the therapy of anginal syndromes is controversial.