How is nitroglycerin metabolized

Nitroglycerin has a large volume of distribution due to its high liposolubility and to tissular protein binding. Nitroglycerin metabolites are excreted through the kidneys. For the acute treatment of angina, nitroglycerin is available as capsules to be chewed, sublingual tablets and mouth spray. Injection solutions are available for the treatment of conditions such as acute myocardial infarction. For long-term treatment of angina, controlled-release capsules, transdermal patches and skin ointment are available.

Long term use of nitroglycerin leads to tolerance, unless the treatment is discontinued daily for a period of 10 to 12 hours. Indocyanine green, a non-substrate inhibitor of glutathione S-transferase, inhibited GTN metabolism by smooth muscle cells.

Cellular glutathione is also involved in GTN metabolism by the smooth muscle cell. Pretreatment with phorone, a glutathione S-transferase substrate, depleted cellular glutathione and decreased nitrite production from GTN. Pretreatment with buthionine sulfoximine, inhibitor of gamma-glutamylcysteine synthetase, decreased intracellular glutathione and caused decreased GTN metabolism in smooth muscle cells.

Removal of cysteine from the smooth muscle cell incubation medium in combination with buthionine sulfoximine pretreatment decreased GTN metabolism to a lower level than buthionine sulfoximine pretreatment alone. This study shows that glutathione S-transferase and glutathione are involved in GTN metabolism by cultured smooth muscle cells. Abstract Metabolism of nitroglycerin GTN in the vascular smooth muscle is required for the drug to be effective in the treatment of angina pectoris and congestive heart failure.

Publication types Research Support, Non-U.