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Glyceryl Trinitrate Case Study

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Glyceryl trinitrate (GTN) is commonly used as a preventer and reliever of pain associated with a lack of oxygen perfusing the myocardium. The mechanism of action of GTN is widely disputed. However it is widely believed that aldehyde dehydrogenase 2 (ALDH2) catalyses the bioactivation of GTN into nitric oxide (NO). NO then initiates guanylyl cyclase to synthesise cyclic guanosine monophosphate (cGMP). cGMP then induces vascular smooth muscle relaxation via the second messenger system (Marsh & Marsh, 2000). This relaxation results in dilation of arteries and veins. The widening of these vessels reduces preload and afterload, therefore reducing the amount of oxygen demanded by the heart. Vasodilation leads to a decrease in vascular resistance and as a consequence significantly reduces venous and arterial blood pressure, a side effect that needs to be closely monitored …show more content…
GTN reduces the amount of oxygen required by the heart and increases the amount of oxygen supplied to the heart, in turn, inducing a decline in ischemia and pain associated with an AMI. Ferreira & Mochly-Rosen (2012) suggest that continued use of GTN increases the magnitude of an infarct and cardiac impairment post AMI. This study indicates that the persistent use of GTN causes intermolecular disulphide bonds to form in the active site of ALDH2, therefore rendering it inactive and incapable to catalyse the reaction of GTN to NO. ADLH2 is responsible for the elimination of cytotoxic aldehydes that gather in events like ischemia. Rats administered with GTN prior and after an AMI displayed greater irreversible cardiac damage than those who received no GTN or received concurrent treatment with an Alda-1 (an ALDH2 activator). This study would suggest that the use of GTN might be more effective in short-term use or with periods of abstinence (Ferreira & Mochly-Rosen,

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