Nitrates angina pectoris

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... 

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. 

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. O2 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 main drngs nsed for myocardial ischema therapy and for relieving pain in angina pectoris are nitrates and nitrites (nitroglycerin, isosorbide dinitrate, and pentaerythritol tetranitrate) snbstances that snppress adrenergic systems of the heart—j3-adrenoblockers (atenolol, methoprolol, propranolol, and nadolol), and Ca + channel blockers (verapamil, diltiazem, nifedipine, and nicardipine) as well as a few older drugs, in particular papaverine and dipyridamole. 

More than 100 years ago, it was observed that amylnitrate and nitroglycerine relieve pain in angina pectoris, and since nitrites and nitrates have the ability to dilate vessels, thus moderately increasing blood flow to the myocardium, it became customary to think that dilation of coronary vessels alleviates the condition of angina pectoris. 

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

Nitrate-free interval Several clinical trials of nitroglycerin in patients with angina pectoris have evaluated regimens that incorporated a 10- to 12-hour nitrate-free interval. 

TABLE 17.2 Dosage Forms and Pharmacokinetics of Nitrates Most Commonly Used in Angina Pectoris... 

Parker JD and Parker JO. Drug therapy Nitrate therapy for stable angina pectoris. N Engl J Med... 

Uses of NG. Aside from die expl uses discussed under Dynamite and Smokeless Powder (NG gelled with NC), the only extensive use for NG is as a decrease of blood pressure in the treatment of angina pectoris where It is in competition with other polyol nitrates. There is voluminous literature on the pros, aons, and wherefores of this subject... 

Angina pectoris, hypertension, congestive heart failure, acute myocardial ischaemia, acute pulmonary oedema, unstable coronary syndromes especially when associated with elevated filling pressures. Nitrate therapy may exaggerate outflow obstruction in hypertrophic obstructive cardiomyopathy. 

Table 12-7 Effects of Nitrates Alone and with Blockers or Calcium Channel Blockers in Angina Pectoris. ...

The latest entrant in the neurotransmitter lineup is NO, nitric oxide, the first neurotransmitter discovered in the gas phase. For decades physicians and pharmacologists have been aware of the ability of nitrates to dilate blood vessels. Compounds like nitroglycerin are key tools in the control of angina pectoris, constriction of the coronary arteries. Yet no one knew exactly how the nitrates performed their feat until recently. The notariety of Viagra attests to the interest in products which affect NO systems. More about the synthesis and actions of NO will be described shortly. 

Uses Prevention/Rx of angina pectoris Action Relaxes vascular smooth muscle Dose 5-10 mg PO bid, w/ the 2 doses 7 h apart or XR (Imdur) 30-60 mg/d PO, max 240 mg Caution [C, ] Contra Head trauma/cerebral hemorrhage (can ICP), w/ sildenafil, tadalafil, vardenafil Disp Tabs 10, 20 mg XR 30, 60, 120 mg SE HA, dizziness, X- BP Interactions T Hypotension W/ ASA, CCB, nitrates, sildenafil, EtOH EMS Metabolite of isosorbide dinitrate use ASA, antihypertensives, and CCBs w/ caution, may T hypotension concurrent Viagra-type drug use can lead to profound hypotension concurrent EtOH use can T effects OD May cause N/V, profound hypotension, skin flushing, HA from ICP, bradycardia, confusion, and circulatory collapse activated charcoal may be effective, epi use is contraindicated... 

---