[Nitroglycerin preparations. Effect and tolerance]

Abstract

Nitroglycerin and other organic nitrates are beneficial in ischaemic heart disease and myocardial infarction and as adjunctive therapy in congestive heart failure. The nitrates are inactive prodrugs, and their vascular effects depend on metabolic conversion to vasoactive intermediates like nitric oxide and/or nitrosothiols with subsequent stimulation of guanylate cyclase causing increased formation of cyclic GMP. The compounds relax vascular smooth muscle producing venous dilatation at low concentrations and at higher concentrations dilation of coronary arteries and collaterals and systemic arterial vessels. Nitrate tolerance is, however, a problem with continuous nitrate therapy. Tolerance is most likely to occur with frequent dosing or with the use of long-acting nitrates or transdermal applications resulting in constant plasma concentrations. Therapeutic strategies should be designed to provide a daily low-nitrate period or nitrate-free period to obviate the development of tolerance and thus maintain the antianginal effects.