Organic nitrates in their second century

Abstract

An updated review of the organic nitrates that were introduced in the therapeutics of ischemic heart disease almost a century and a half ago was made. This group of drugs induce the formation of nitric oxide in the cell of the arterial smooth muscle, provoking this way an increase of the levels of cyclic guanosine monophosphate that, at the same time, reduces the cytosolic concentration of calcium ion, causing mainly venous vasodilation. The reduction of the venous return to the heart reduces heart work and the consumption of myocardial oxygen. As their clinical efficiency has been largely demonstrated, these drugs are still first-line drugs in the treatment of various cardiac affections. A very important adverse effect is tolerance, which has led to the search of therapeutic combinations of nitrates to achieve its reduction. However, it seems that the fundamental thing is to attain a nitrate-free period, to reduce the dose to the minimum and to avoid the administration of some sustained-release drugs that give rise to this event. It seems reasonable to assume that cross tolerance may occur among nitrates, which would reduce the efficiency of the treatment of anginal crises. Another adverse effect is the syndrome of suppression that may cause an increase of the frequency and severity of ischemic crises.