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Disulfiram Reaction

Disulfiram Reaction is a topic covered in the 5-Minute Emergency Consult.

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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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Citation

Rosen, Peter, et al., editors. "Disulfiram Reaction." 5-Minute Emergency Consult, 5th ed., Lippincott Williams & Wilkins, 2016. Emergency Central, emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307162/all/Disulfiram_Reaction.
Disulfiram Reaction. In: Rosen P, Shayne P, Barkin AZ, et al, eds. 5-Minute Emergency Consult. 5th ed. Lippincott Williams & Wilkins; 2016. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307162/all/Disulfiram_Reaction. Accessed April 25, 2019.
Disulfiram Reaction. (2016). In Rosen, P., Shayne, P., Barkin, A. Z., Wolfe, R. E., Hayden, S. R., Barkin, R. M., & Schaider, J. J. (Eds.), 5-Minute Emergency Consult. Available from https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307162/all/Disulfiram_Reaction
Disulfiram Reaction [Internet]. In: Rosen P, Shayne P, Barkin AZ, Wolfe RE, Hayden SR, Barkin RM, Schaider JJ, editors. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2016. [cited 2019 April 25]. Available from: https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307162/all/Disulfiram_Reaction.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Disulfiram Reaction ID - 307162 ED - Rosen,Peter, ED - Shayne,Philip, ED - Barkin,Adam Z, ED - Wolfe,Richard E, ED - Hayden,Stephen R, ED - Barkin,Roger M, ED - Schaider,Jeffrey J, BT - 5-Minute Emergency Consult UR - https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307162/all/Disulfiram_Reaction PB - Lippincott Williams & Wilkins ET - 5 DB - Emergency Central DP - Unbound Medicine ER -