Disulfiram Reaction

Basics

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

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