N-acetylcysteine is useful for treatment of toxicity due to:
Ans. A. Acetaminophen. (Ref. KDT 6th/pg. 199)AcetaminophenMechanismReversibly 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 mg/mL measured at 4 h or >100 mg/mL 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 mg/kg 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 acetaminophen/Paracetamol poisoning (replenishes glutathione).# To prevent Contrast induced nephropathy.
Acetaminophen
Cyclophosphamide
Aspirin
Methyl dopa
Miscellaneous (Pharmacology)