Calcium ions, drug action and the heart--with special reference to calcium antagonist drugs.
Calcium antagonists, of which the best known are verapamil, nifedipine and diltiazem, are a powerful group of cardioactive agents with a clinical spectrum of indications rather similar to those of beta-adrenoceptor blockade, including angina of effort, angina at rest, hypertension and supraventricular tachycardias (nifedipine is ineffective for the latter). In angina caused by coronary spasm, calcium antagonists are preferred to beta-blockade. Calcium antagonists have a basically different mode of action from beta-adrenoceptor blockade, although both ultimately act on the free cytoplasmic calcium ion concentration. Critical differences between the calcium antagonists are dependent on the individual properties of the calcium antagonists concerned. Different binding sites on the sarcolemma have been identified for nifedipine-like agents and verapamil, but with a different interaction with the nifedipine site. None of these sites might be relevant to the binding of calcium antagonists to the tissue of their therapeutic site of action (arterial smooth muscle for all; atrioventricular node for verapamil and diltiazem). As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients, these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed, especially in the case of nifedipine. The clinical differences between the effects of various calcium antagonists reflect: (i) the greater vasodilator capacity of nifedipine, so that at a given concentration the afterload effect dominates over possible effects on the nodal or myocardial tissue; (ii) the greater inhibition of vagal tone by nifedipine than by verapamil or diltiazem; and (iii) the greater inhibition of the atrioventricular node by verapamil and diltiazem. In angina of effort, calcium antagonists are now becoming the agents of first choice in some centers. Experimental use of calcium antagonists include the possible prevention of ventricular fibrillation, the inhibition of ischemic injury, the prevention of catecholamine mediated injury to the myocardium and decreased arterial calcinosis.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000787:Angina Pectoris / Q000188:drug therapy; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002395:Catecholamines / Q000494:pharmacology; D003327:Coronary Disease / Q000517:prevention & control; D003329:Coronary Vasospasm / Q000188:drug therapy; D003331:Coronary Vessels / Q000502:physiology; D004077:Digoxin / Q000494:pharmacology; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy; D009206:Myocardium / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects; D013329:Structure-Activity Relationship; D014693:Ventricular Fibrillation / Q000188:drug therapy
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D002395:Catecholamines; D004077:Digoxin; D002118:Calcium; D011224:Prazosin