Organic nitrates angina pectoris

Mechanism of Relief of Symptoms of Angina Pectoris The nitrate-induced relief of anginal pain has been ascribed to a decrease in cardiac work secondary to the fall in systemic arterial pres-sine. The ability of nitrates to dilate epicardial coronary arteries is modest the bulk of evidence favors a reduction in myocardial work and thus in myocardial oxygen demand as their primary effect in chronic stable angina. Paradoxically, high doses of organic nitrates may reduce blood pres-sine to such an extent that coronary flow is compromised reflex tachycardia and adrenergic... 

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... 

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

P. Needleman, S. Lang, E. M. Johnson Jr., Organic Nitrates Relationship between Biotransformation and Rational Angina Pectoris Therapy , J. Pharmacol. Exp. Then 1972, 181, 489 - 497. 

The mechanism by which organic nitrates relieve the pain of angina pectoris was not discovered until nitric oxide was identified as the agent which was responsible for vasodilation of arteries. It was known for many years that endothelial cells released a factor that resulted in vasodilation a factor appropriately called endothelial relaxing factor (EDRF). It was, however, some time before the factor was identified, probably because it turned out to be a gas - nitric oxide - which was totally unexpected. Nitric oxide is now known to be a very important messenger molecule involved in the regulation of many other systems. The mechanism by which it causes vasodilation is described in Chapter 13. 

Uses. Organic nitrates are used chiefly in angina pectoris (p. 308, 310), less frequently in severe forms of chronic and acute congestive heart failure. Continuous intake of higher doses with maintenance of steady plasma levels leads to loss of efficacy, inasmuch as the organism becomes refractory (tachy-phylactic). This nitrate tolerance can be avoided if a daily nitrate-free interval is maintained, e.g., overnight. 

CHF associated with acute Ml treatment of angina pectoris unresponsive to organic nitrates or -blockers production of controlled hypotension during surgical procedures. 

Organic nitrates (and nitrites) are simple nitric and nitrous acid esters of alcohols. They differ in their volatility for example, isosorbide dinitrate is solid at room temperature, nitroglycerin is only moderately volatile, whereas amyl nitrate is extremely volatile. These compounds cause a rapid reduction in myocardial oxygen demand followed by rapid relief of symptoms. They are effective in stable and unstable angina, as well as Prinzmetal s or variant angina pectoris. 

Organic nitrates (A) increase blood flow, hence 02 supply, because diastolic wall tension (preload) declines as venous return to the heart is diminished. Thus, the nitrates enable myocardial flow resistance to be reduced even in the presence of coronary sclerosis with angina pectoris. In angina due to coronary spasm, arterial dilation overcomes the vasospasm and restores myocardial perfusion to normal. 02 demand falls because of the ensuing decrease in the two variables that determine systolic wall tension (afterload) ventricular filling volume and aortic blood pressure. 

The organic nitrate nitroglycerin or glyceryl tri nitrate (GTN) a polyol ester of nitric acid was first synthesised in 1846 by Sobrero as an explosive and reported as a therapeutic agent in 1879 by Murrell for the relief and prophylaxis of angina pectoris. This was preceded by the use of the organic nitrite, amylnitrite, in 1857 for the treatment of angina and was the first described use of a nitrovasodilator. 

Organic nitrates have been in use for over 135 years, and their adverse effects are therefore weU documented. The first compound of this class to be used was amyl nitrite, synthesized in 1844 by Ballard and used to treat angina pectoris by Brunton in 1869. Glyceryl trinitrate was first synthesized by Ascagne Sobrero in 1847 and was used by William Murrell to treat angina pectoris in 1879. 

---