Heart failure, chronic nitrates

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. 

Examples of specific drugs used in the treatment of chronic heart failure include digitalis glycosides (e.g., digoxin, positive inotropic agent), diuretics (hydrochlortiazide and furosemide), and vasodilators (nitrates such as nitroglycerin, ACE inhibitors, such as captopril, and hydralazine). 

Cardiac work furthermore depends strongly on the state of the circulation system physical rest or work demand appropriate cardiac performance the level of mean blood pressure is an additional decisive factor. Chronic elevation of afterload leads to myocardial insuf ciency. Therefore, all blood pressure-lowering drugs can have an important therapeutic influence on the myocardium. Vasodilator substances (e.g., nitrates) lower the venous return and/or peripheral resistance and, hence, exert a favorable effect in angina pectoris or heart failure. 

Elkayam U, Johnson JV, Shotan A, Bokhari S, Solodky A, Canetti M, Wani OR, Karaalp IS. Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition. Circulation 1999 99(20) 2652-7. 

Watanabe H, Kakihana M, Ohtsuka S, Sugishita Y. Randomized, double-blind, placebo-controUed study of carvedilol on the prevention of nitrate tolerance in patients with chronic heart failure. J Am CoU Cardiol 1998 32(5) 1194-200. 

Massie, B., Chatterjee, K., Werner, J., Greenberg, B., Hart, R., and Parmley, W. W. (1977). Hemodynamic advantage of combined administration of hydralazine orally and nitrates nonparenterally in the vasodilator therapy of chronic heart failure. Am. J. Cardiol. 40, 794-801. 

Amrinone has been approved for use in the United States for the short-term management of congestive heart failure. The major use of digitoxin is in the treatment of chronic mild heart failure, frequently in combination with an angiotensin converting enzyme (ACE) inhibitor. This combination also is effective in the treatment of the acute condition. Nitroglycerin is representative of the nitrates used for the treatment of angina pectoris. 

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