Calcium antagonists. Pharmacodynamic effects and mechanism of action

Calcium antagonistic drugs (also called slow channel or calcium channel inhibitors or calcium entry blockers) represent a major development in cardiovascular pharmacology. Their main site of action is at the slow channels where they inhibit Ca2+ influx into the cells. This characteristic distinguishes them from other drugs such as sodium nitroprusside, papaverine, hydralazine and diazoxide which interfere with the availability of calcium ions for their physiological functions by acting at sites other than the 'calcium channels'. There is considerable evidence, however, that calcium antagonistic drugs act at an intracellular site(s) as well as the 'calcium channels'. At present, verapamil, nifedipine and diltiazem are the most important representatives of this new class of drugs. Their chemical structures are quite different but their pharmacological characteristics are similar. The action of these drugs is primarily confined to the cardiovascular system. In the heart they depress cardiac contractions and heart rate and protect the ischaemic myocardium from calcium injury. Furthermore, verapamil and diltiazem (but not nifedipine) prolong AV conduction and refractoriness, which is important for their use as antiarrhythmic agents. All 3 drugs are powerful dilators of the coronary and peripheral arteries. These in vitro effects can be substantially altered by activation of baroreceptor reflexes in vivo, as is expected with vasodilators that cause little or no inhibition of noradrenaline release from sympathetic nerve endings. The combination of coronary dilatation with decreased oxygen demand of the myocardium and with decreased preload explains their value in the treatment of vasospastic and effort angina.