Vasodilators calcium channel-blocking drugs

Thus, the individual pharmacological effects exerted by each calcium channel blocker may depend upon the extent to which the drug affects other intracellular systems as well as its potency at the calcium channel. Many of the effects described here would tend to increase the vasodilator action of the drugs, such as inhibition of calmodulin-dependent enzymes. However, these other effects are subsidiary to blockade of the calcium channel, as they occur mainly at concentrations higher than those required to block the channels therefore, at low concentrations the actions of the calcium channel blocking drugs are relatively specific. 

Double-blind placebo-controlled trials have shown that both nifedipine and diltiazem are effective in controlling the symptoms of Raynaud s phenomenon [213-215]. Nifedipine increases fingertip blood flow by decreasing fingertip vascular resistance [216]. At present, the sole calcium channel blocking drug to have been licensed in the U.K. for the treatment of Raynaud s phenomenon is nifedipine. Since all calcium channel blockers produce vasodilation, they may all eventually prove to be effective in counteracting vasoconstriction in patients with Raynaud s phenomenon, but this has yet to be established. 

Calcium channel blocking agents, such as verapamil and nifedipine are also satisfactory antihypertensive agents. These drugs reduce the influx of calcium ions into vascular muscle cells following excitation and so cause vasodilation. They act mainly on arterial vessels in the circulation. 

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 It has been used in the treatment of angina pectoris, but it often causes ventricular dysrhythmias and has been superseded by less toxic drugs. 

Calcium channel antagonists enhance vasodilation by blocking L-type Ca2+ channels in cardiac and vascular tissues. They are particularly effective for elderly and African American patients. Drugs considered are verapamil, diltiazem, nifedipine, and nimodipine. 

Pharmaceutical chemists, too, have evinced a keen interest in DHA chemistry, particularly the 4-aryldihydropyridines, which exhibit powerful vasodilating activities via the blocking of calcium channels and modifying movement of Ca2+ into and within the cell. The explosion in activity in this area of heterocyclic synthesis has produced an exponential growth in patent applications and papers and has led to the marketing of a new drug, nifedipine (4).6 Other active 4-aryldihydropyridine derivatives, such as nimodipine and nicardipine (cerebral vasodilators) and nitrendipine (antihypertensive), are presently under clinical trials.7 An excellent list of other practical applications of dihydropyridines has been collected by Kuthan and Kurfiirst.2... 

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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