<prompt> N-acetylcysteine is useful for treatment of toxicity due to:AcetaminophenCyclophosphamideAspirinMethyl dopa  <response>: Ans. A. Acetaminophen. Ref. KDT 6thpg. 199AcetaminophenMechanismReversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.CliniCal useAntipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in children with viral infection.ToxicityOverdose produces hepatic necrosis; acetaminophen metabolite NAPQI depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote--regenerates glutathione.ACETAMINOPHEN OVERDOSAGEAcetaminophen is metabolized predominantly by a phase II reaction to innocuous sulfate and glucuronide metabolites.Acetaminophen can cause severe centrilobular hepatic necrosis when ingested in large amounts.Fatal fulminant disease is usually associated with ingestion of micro25 g. Blood levels of acetaminophen correlate with the severity of hepatic injury levels 300 microg mL 4 h are predictive of the severe damage; levels 150 microg mLsuggest that hepatic injury is highly unlikely. Renal failure and myocardial injury may be present.Rx: Treatment includes gastric lavage, supportive measures, and oral administration of activated charcoal or cholestyramine to prevent absorption of residual drug effective if given 30 min after ingestion. In patients with high acetaminophen blood levels 200 mgmL measured at 4 h or 100 mgmL at 8 h after ingestion, the administration of sulfhydryl compounds e.g., cysteamine, cysteine, or N-acetylcysteine reduces the severity of hepatic necrosis. It appear to act by providing a reservoir of sulfhydryl groups to bind the toxic metabolites or by stimulating synthesis and repletion of hepatic glutathione. Therapy should be begun within 8 h of ingestion but may be effective even if given as late as 24-36 h after overdose. Later administration of sulfhydryl compounds is of uncertain value. Routine use of N-acetylcysteine has substantially reduced the occurrence of fatal acetaminophen hepatotoxicity. When given orally, N- acetylcysteine is diluted to yield a 5 solution. A loading dose of 140 mg kg is given, followed by 70 mgkg every 4 h for 15-20 doses. Rx can be stopped when plasma acetaminophen levels indicate that the risk of liver damage is low. If signs of hepatic failure e.g., progressive jaundice, coagulopathy confusion occur despite N-acetylcysteine therapy for acetaminophen hepatotoxicity, liver transplantation is only option.Uses of N-acetylcysteine Mucolytic cleaves disulfide bonds within mucus glycoproteins, e.g. in CF. Antidote of acetaminophenParacetamol poisoning replenishes glutathione. To prevent Contrast induced nephropathy. 