Pharmacology of Nitrovasodilators

There are two classes of nitrovasodilators used clinically: the organic nitrates (nitroglycerin, isosorbide dinitrate, and isosorbide-5-mononitrate) and the metal nitrosyls (sodium nitroprusside).Nitrovasodilators themselves are inactive and must release vasoactive nitric oxide (NO) or its related species to exert their pharmacological effects. The metabolic end-products of nitrovasodilators are nitrite and nitrate, and increased exposure to these ions can be significant especially when nitrovasodilators are used on a chronic basis.In addition to their effects on vasotone, nitrovasodilators are also potent anti-platelet agents.Nitrovasodilators are used for the management of several cardiovascular pathologies including stable and unstable angina, congestive heart failure, and myocardial infarction.Metabolism of organic nitrates can be categorized as mechanism-based (releasing NO) or clearance-based (releasing nitrite). Various enzymes, including mitochondrial aldehyde dehydrogenase and glutathione-S-transferase, play key roles in these processes.Tolerance to the vasodilatory effects of organic nitrates is mediated via oxidation of multiple protein cysteine groups, producing a myriad of downstream events. A nitrate-free period is used clinically to circumvent this loss of efficacy.Organic nitrates can induce endothelial dysfunction through increased oxidative stress and several studies have questioned the long-term safety of these agents.Cyanide radical release from the nitroprusside complex and its rapid elimination precludes the use of sodium nitroprusside on a chronic basis. There are two classes of nitrovasodilators used clinically: the organic nitrates (nitroglycerin, isosorbide dinitrate, and isosorbide-5-mononitrate) and the metal nitrosyls (sodium nitroprusside). Nitrovasodilators themselves are inactive and must release vasoactive nitric oxide (NO) or its related species to exert their pharmacological effects. The metabolic end-products of nitrovasodilators are nitrite and nitrate, and increased exposure to these ions can be significant especially when nitrovasodilators are used on a chronic basis. In addition to their effects on vasotone, nitrovasodilators are also potent anti-platelet agents. Nitrovasodilators are used for the management of several cardiovascular pathologies including stable and unstable angina, congestive heart failure, and myocardial infarction. Metabolism of organic nitrates can be categorized as mechanism-based (releasing NO) or clearance-based (releasing nitrite). Various enzymes, including mitochondrial aldehyde dehydrogenase and glutathione-S-transferase, play key roles in these processes. Tolerance to the vasodilatory effects of organic nitrates is mediated via oxidation of multiple protein cysteine groups, producing a myriad of downstream events. A nitrate-free period is used clinically to circumvent this loss of efficacy. Organic nitrates can induce endothelial dysfunction through increased oxidative stress and several studies have questioned the long-term safety of these agents. Cyanide radical release from the nitroprusside complex and its rapid elimination precludes the use of sodium nitroprusside on a chronic basis.