Angina nitrates

Each of the transdermal nitroglycerin systems is effective in treating angina pectoris when worn for 12—16 h followed by an off period. The FDA recommends the period without dmg (8—12 h) to mitigate the possibiUty of the patient acquiring a tolerance to the antianginal effects of nitrate therapy. Thus, a noncontinuous dosing schedule of nitrates is recommended even with the transdermal deflvery system (81). 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

Control of blood pressure in perioperative hypertension and in immediate postoperative period, CHF associated with acute Ml, angina pectoris unresponsive to recommended doses of nitrates or beta blockers... 

In many instances, the adverse reactions associated with tlie nitrates lessen and often disappear with prolonged use of die drug. However, for some patients, tiiese adverse reactions become severe, and the primary health care provider may lower the dose until symptoms subside The dose may then be slowly increased if the lower dosage does not provide relief from the symptoms of angina... 

Nitrate products are available in both oral and transdermal formulations for chronic use. Commonly used products are listed in Table 4-8. All nitrate products are equally effective at preventing the recurrence of angina when used appropriately. 

The answer is d. (Hardman, pp 767—775.) Ca channel blockers, of which nifedipine is a prime example, are now considered to be more effective than nitrates in relieving variant angina This is because this type of angina is believed to be caused by vasospasm, which is best antagonized by slow-channel Ca blockers. Such blockers appear to have a relative selectivity for coronary arteries. 

The answer is a. (Hardman, pp 762-764.) Experimentally, nitrates dilate coronary vessels. This occurs in normal subjects, resulting in an overall increase in coronary blood flow. In arteriosclerotic coronaries, the ability to dilate is lost, and the ischemic area may actually have less blood flow under the influence of nitrates. Improvement in the ischemic conditions is the result of decreased myocardial oxygen demand because of a reduction of preload and afterload. Nitrates dilate both arteries and veins and thereby reduce the work of the heart. Should systemic blood pressure fall, a reflex tachycardia will occur. In pure coronary spasm, such as Prinzmetal s angina, the effect of increased coronary blood flow is relevant, while in severe left ventricular hypertrophy with minimal obstruction, the effect on preload and afterload becomes important. 

If /1-blockers are ineffective or not tolerated, then monotherapy with a calcium channel antagonist or combination therapy may be instituted. Reflex tachycardia from nitrates can be blunted with /1-blocker therapy, making this a useful combination. Patients with severe angina, rest angina,... 

Because calcium channel antagonists may be more effective, have few serious adverse effects, and can be given less frequently than nitrates, some authorities consider them the agents of choice for variant angina. Nifedipine, verapamil, and diltiazem are all equally effective as single agents for... 

E. M., Organic nitrates. Relationship between biotransformation and rational angina pectoris therapy. J. Pharmacol. Exp. Ther. 181 (1972), p. 489-497... 

A number of organic nitrates are potent vasodilators and have been used clinically for over lOOyears, particularly for the relief of the symptoms of angina (Fig. 8.6). The most widely used is glyceryl trinitrate (GTN) but the group includes pentaerythrityl tetranitrate (PETN), isosorbide mononitrate (ISMO) andisosorbide dinitrate (ISDN). 

Over a century ago, empirical observation was made that organic nitrates, including glyceryl trinitrate (GTN), alleviate angina. Since then, GTN has been a mainstay therapy for angina and cardiac failure, even with the possible loss of effectiveness (tolerance) over extended dosing [55] and the risk of platelet hyperactivity in GTN-tolerant patients [54]. Despite this venerable therapeutic history, the mechanism of GTN bioactivation to NO is speculative at best [38]. In 1967, some 15 years before identification of NO as a biological entity, GTN was the first nitrovasodilator shown... 

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