Disulfiram Reaction

Basics

Description

  • Inhibits various enzymes and its active metabolites exert additional effects
  • Disulfiramethanol reaction:
    • Usually occurs 8–12 hr after taking the drug; should not be observed >24 hr after dosing
    • Competitively and irreversibly inactivates aldehyde dehydrogenase
    • Ethanol metabolism is blocked, resulting in accumulation of acetaldehyde
    • Acetaldehyde produces release of histamine resulting in vasodilation and hypotension
    • Severe reactions may occur in drinkers with ethanol levels of 50–100 mg/dL
    • Severity and duration of reaction is proportional to amount of ethanol ingested
  • Disulfiram blocks dopamine β-hydroxylase and limits synthesis of norepinephrine from dopamine:
    • Relative excess of dopamine may contribute to altered behavior
    • Relative depletion of norepinephrine may contribute to hypotension
  • Disulfiram metabolite (carbon disulfide) interacts with pyridoxal 5-phosphate:
    • Diminishes concentration of pyridoxine available for formation of γ-aminobutyric acid (GABA) in CNS
    • Potentially lowers seizure threshold
    • Carbon disulfide is also cardiotoxic, hepatotoxic, and inhibits cytochrome P-450 (CYP2E1)
  • Disulfiram metabolites may chelate important metals (copper, zinc, iron) essential in various enzyme systems
  • Disulfiram metabolites may cause peripheral neuropathies that are dose and duration dependent

Etiology

  • Disulfiram is used as a deterrent in the treatment of chronic ethanol abuse
  • Many users of the medication wear a medical alert bracelet
  • Other agents producing disulfiram-like reactions:
    • Antibiotics:
      • Metronidazole
      • Cephalosporins (with nMTT side chain)
        • Cefoperazone, cefotetan, cefmetazole
      • Nitrofurantoin
    • Oral hypoglycemics:
      • Sulfonylureas
    • Industrial agents:
      • Carbon disulfide
      • Hydrogen sulfide
    • Mushrooms:
      • Coprinus atramentarius
      • Clitocybe clavipes

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