Drug of choice in paracetamol overdose: March 2011
Correct Answer: N-acetyl cysteine
Description: Ans. A: N-acetyl cysteine In paracetamol poisoning, depletion of hepatic and renal glutathione potentiates the toxicity whereas treatment with sulfhydryl compounds such as cysteamine, 1- methionine and N-acetyl cysteine (NAC) is beneficial Acetylcysteine/ N-acetylcysteine/ N-acetyl-L-cysteine/ NAC) It is used primarily as a mucolytic agent and in the management of paracetamol (acetaminophen) overdose. Other uses include sulfate repletion in conditions, such as autism, where cysteine and related sulfur amino acids may be depleted. Acetylcysteine is a derivative of cysteine; an acetyl group is attached to the nitrogen atom. It is used as a cough medicine because it breaks disulfide bonds in mucus and liquefies it, making it easier to cough up. It is also this action of breaking disulfide bonds that makes it useful in thinning the abnormally thick mucus in Cystic Fibrosis patients Intravenous acetylcysteine is indicated for the treatment of paracetamol (acetaminophen) overdose. When paracetamol is taken in large quantities, a minor metabolite called N-acetyl- p-benzoquinone imine (NAPQI ) accumulates within the body. It is normally conjugated by glutathione, but when taken in excess, the body's glutathione reserves are not sufficient to inactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, therefore damaging hepatocytes. This may lead to severe liver damage and even death by fulminant liver failure. For this indication, acetylcysteine acts to augment the glutathione reserves in the body and, together with glutathione, directly bind to toxic metabolites. These actions serve to protect hepatocytes in the liver from NAPQI toxicity. Although both IV and oral acetylcysteine are equally effective for this indication, oral administration is poorly tolerated because high oral doses are required due to low oral bioavailability, because of its very unpleasant taste and odour, and because of adverse effects, paicularly nausea and vomiting. Inhaled acetylcysteine is indicated for mucolytic ("mucus-dissolving") therapy as an adjuvant in respiratory conditions with excessive and/or thick mucus production.
Category:
Pharmacology
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