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This article is about the pharmacological effects of glyceryl trinitrate. For the chemical properties, see Nitroglycerin.
Glyceryl trinitrate (GTN) has been used to treat angina and heart failure for over 130 years, despite this the mechanism of nitric oxide (NO) generation from GTN and the metabolic consequences of this bioactivation are still not entirely understood. In medical circles it is often referred to as "Nitro."
Denitration of Glyceryl Trinitrate
GTN is a prodrug which must first be denitrated to produce the active metabolite NO. Nitrates which undergo denitration within the body to produce NO are called nitrovasodilators and their denitration occurs via a variety of mechanisms. The mechanism by which nitrates produce NO is widely disputed. Some believe that nitrates produce NO by reacting with sulfhydryl groups, while others believe that enzymes such as glutathione S-transferases, cytochrome P450 (CYP), and xanthine oxidoreductase are the primary source of GTN bioactivation. In recent years a great deal of evidence has been produced which supports the belief that clinically relevant denitration of GTN to produce 1,2-glyceryl dinitrate (GDN) and NO is catalysed by mitochondrial aldehyde dehydrogenase (mtALDH). NO is a potent activator of guanylyl cyclase (GC) by heme-dependent mechanisms; this activation results in cGMP formation from guanosine triphosphate (GTP). Thus, NO increases the level of cGMP within the cell.
Uses
It is more useful in preventing angina attacks than reversing them once they have commenced. Patches of glyceryl trinitrate with a long activity duration are commercially available. It may also be given as a sublingual dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack.
Advantages
Long acting Nitrates can be more useful as they are generally more effective and stable in the short term.
Disadvantages
After long term use for treating chronic conditions, tolerance may develop in a patient reducing its effectiveness.
"Glyceryl trinitrate (pharmacology)"