VPT 421: Veterinary Toxicology (2+0)

ALTERATION OF DRUG METABOLISM

• n-acetylcysteine
  • n-acetylcysteine is a reducing agent that counteracts acetaminophen toxicity.
  • It is most effective if given within 8 – 16 hours of ingestion of the toxicant.
  • Acetaminophen is metabolized in part by cytochrome P450 to an extremely reactive elecrophiloic metabolite which can covalently bind to cell constituents in the hepatocytes where it is formed, resulting in hepatic necrosis.
  • Binding to hepatic glutathione normally detoxifies this type of electrophilic compound.
  • In acetaminophen overdose, hepatic stores of glutathione are inadequate.
  • A structurally similar compound, n-acetylcysteine, acts as glutathione surrogate and prevents toxicity.
• Ethanol
  • The toxic effects of methanol or ethylene glycol are due to metabolism via alcohol dehydrogenase to toxic acids.
  • Ethanol can compete with methanol or ethylene glycol for alcohol dehydrogenase and thereby reduce the rate of formation of toxic acids.