Angina calcium channel-blocking drugs

The Hantzsch pyridine synthesis is an old discovery (1882) which sprang into prominence in the 1980s with the discovery that the dihydropyridine intermediates prepared from aromatic aldehydes are calcium channel blocking agents and therefore valuable drugs for heart disease with useful effects on angina and hypertension. 

Prenylamine is a coronary vasodilator that depletes myocardial catecholamine stores and has some calcium-channel blocking activity. It has been used in the treatment of angina pectoris, but it often causes ventricular dysrhythmias and has been superseded by less toxic drugs. 

Opie LH. First-line drugs in chronic stable effort angina The case for newer, longer-acting calcium channel blocking agents. J Am Coll Cardiol 2000 36 1967-1971. 

L A patient comes to your office with effort-induced angina and resting tachycardia. You choose the following drug to treat the patient because it slows heart rate by blocking L-type calcium channels in the SA node ... 

Cardiac muscle is highly dependent on calcium influx for normal function. Impulse generation in the sinoatrial node and conduction in the atrioventricular node—so-called slow-response, or calcium-dependent, action potentials—may be reduced or blocked by all of the calcium channel blockers. Excitation-contraction coupling in all cardiac cells requires calcium influx, so these drugs reduce cardiac contractility in a dose-dependent fashion. In some cases, cardiac output may also decrease. This reduction in cardiac mechanical function is another mechanism by which the calcium channel blockers can reduce the oxygen requirement in patients with angina. 

Verapamil, diltiazem Nonselective block of L-type calcium channels in vessels and heart Reduced vascular resistance, cardiac rate, and cardiac force results in decreased oxygen demand Prophylaxis of angina, hypertension, others Oral, IV, duration 4-8 h Toxicity Atrioventricular block, acute heart failure constipation, edema Interactions Additive with other cardiac depressants and hypotensive drugs... 

Mibefradil is the first calcium antagonist known to selectively block T-type calcium channels. It is highly effective against hypertension and angina pectoris, and significantly improves the benefit-risk balance in comparison with drugs which have similar targets. 

Calcium antagonists (Figure 4.3) are agents which block the flow of calcium ions into cardiac and vascular smooth muscle when they are stimulated to contract. They have value as vasodilators for use in hypertension and also reduce blood flow resistance and cardiac workload in the treatment of angina. Verapamil (Knoll Pfizer, 1967) is also used as an antiarrhythmic because of its effects on ion channels in the heart s electrical conduction system. Nifedipine (Bayer, 1977) is among the world s top 25 drugs and is the forerunner of several agents of the dihydropyridine class. 

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