Vasodilators Antianginal agents

Bepridil (59) blocks the slow calcium channel and serves as an antianginal agent and a vasodilator. In its synthesis, alcohol (derived from epichlorohydrin) is converted to the corresponding chloride with thionyl chloride and displaced with the sodium salt of ]i-benzylaniline to give bepridil (59) °... 

MecfMnism of Action An antihypertensive and antianginal agent that inhibits calcium movement across cardiacandvascular smooth-musclecell membranes. Potent peripheral vasodilator (does not depress SA or AV nodes). Therapeutic Effect Increases myocardial contractility, heart rate, and cardiac output decreases peripheral vascular resistance and BP. 

Nicorandil and several other investigational antianginal agents appear to combine the activity of nitric oxide release with potassium channel-opening action, thus providing an additional mechanism for causing vasodilation. 

These drugs, of which verapamil is the prototype, were first introduced as antianginal agents and are discussed in greater detail in Chapter 12 Vasodilators the Treatment of Angina Pectoris. Verapamil, diltiazem, and bepridil also have anti arrhythmic effects. 

Four categories of calcium channel blockers can be defined based on their chemical structures and actions diphenylalkylamines, benzothiazepines, dihydropyridines, and bepridil. Both diphenylalkylamines (verapamil) and benzothiazepines (diltiazem) exhibit effects on both cardiac and vascular tissue. With specificity for the heart tissue, these two types of calcium channel blockers can slow conduction through the AV node and are useful in treating arrhythmias. The dihydropyridines (nifedipine is the prototypical agent) are more potent peripheral and coronary artery vasodilators. They do not affect cardiac conduction, but can dilate coronary arteries. They are particularly useful as antianginal agents. Bepridil is unique in that it blocks both fast sodium channels and calcium channels in the heart. All calcium channel blockers, except nimodipine and bepridil, are effective in treating HTN. 

Caplenal allopurinol. capobenate sodium capobenic acid, capobenie acid [inn, usan] (capobenate sodium [usan]) is a benzamido derivative, a VASODILATOR, ANTIARRHYTHMIC and ANTIANGINAL AGENT, used for treatment of cardiac infarction. Capoten captopril. 

Benfurodil (VI) has been claimed to be a cardiotonic-vasodilator, which has clinical value in angina pectoris. However, no data is available. Ildamen (VII) has recently been placed on the European market as an antianginal agent. Ildamen has a positive Inotropic activity and ap-... 

Dipyridamole 2 A, /V,/V, jV -tetrakis-(2-hydroxyethyl)-4,8-dipipcridinopyrimido[5,4- f]-pyrimidine-2,6-diaminc R1 = R2 = piperidino is marketed as a coronary vasodilator. It is used primarily in clinical practice as an antiplatelet agent. Dipyridamole increases the coronary blood flow and was originally introduced as an antianginal agent.179,180 It is usually combined with acetylsalicylic acid for synergistic antiaggregatory purposes.180,181... 

Nicotinic acid and its reduced form, nicotinyl alcohol, have been used for years in attempts to manage peripheral vascular disease. However, nicotinic acid and the alcohol (which is metabolized to the acid) have weak vasodilating activity. At tolerated doses they probably exhibit some activity on dermal blood vessels. The nitrate ester of N-(p-hydrox-yethyl)nicotinamide, nicorandil, was developed in Japan as an antianginal agent. The drug has coronary and peripheral vasodilating properties as well as spasmolytic effects. It thus acts as a classical nitrate. Whether the molecular mechanisms are the same has not been established. 

Mechanism of Action An antianginal, antihypertensive, and antiarrhythmic agent that inhibits calcium movement across cardiac and vascular smooth-muscle cell membranes. This action causes the dilation of coronary arteries, peripheral arteries, and arterioles. Therapeutic Effect Decreases heart rate and myocardial contractility, slows SA and AV conduction, and decreases total peripheral vascular resistance by vasodilation. 

In addition to their antianginal (see Chapter 12 Vasodilators the Treatment of Angina Pectoris) and antiarrhythmic effects (see Chapter 14 Agents Used in Cardiac Arrhythmias), calcium channel blockers also dilate peripheral arterioles and reduce blood pressure. The mechanism of action in hypertension (and, in part, in angina) is inhibition of calcium influx into arterial smooth muscle cells. 

The most signifioant interaotions of organic nitrates are with those agents that cause hypotension, suoh as other vasodilators, alcohol, and tricyclic antidepressants, in which the potential for orthostatio hypotension may arise. On the other hand, concurrent administration with sympathomimetic amines, such as ephedrine and norepinephrine, may lead to a decrease in the antianginal efficacy of the organic nitrates. 

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