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ACUTE EXPOSURE INFORMATION

1. USES: Disulfiram also known as antabuse or tetraethylthiuram disulfide (TETD) is used as an industrial antioxidant, fungicide, disinfectant, and most commonly to maintain sobriety in patients with chronic ethanol abuse. This document discusses toxicity related to disulfiram overdose. Please refer to ETHANOL-DISULFIRAM REACTION or DISULFIRAM-LIKE REACTION documents for more information regarding adverse events from interactions with ethanol.

2. PHARMACOLOGY: Disulfiram inhibits aldehyde dehydrogenase and dopamine betahydroxylase which leads to inhibition of alcohol oxidation at the acetylation stage and results in high levels of acetaldehyde and produces a disulfiram-alcohol reaction.

3. TOXICOLOGY: Disulfiram-induced inhibition of dopamine betahydroxylase results in norepinephrine depletion at presynaptic sympathetic nerve endings. The carbon disulfide metabolite (industrial solvent & pesticide) of acetaldehyde may cause the CNS and peripheral nerve toxicity associated with disulfiram.

4. EPIDEMIOLOGY: Disulfiram overdose alone is uncommon and severe manifestations of toxicity are rare.

5. WITH THERAPEUTIC USE
   1. COMMON: Metallic taste, garlic/sulfur/acetone odor, nausea, vomiting, headache, drowsiness, and ataxia.
   2. RARE: Dermatitis, liver injury (may progress to fulminant hepatic failure), seizure, neuropathy, encephalopathy, and optic neuritis.

6. WITH POISONING/EXPOSURE
   1. MILD TO MODERATE TOXICITY: Nausea, vomiting, abdominal pain, diarrhea, odor of sulfur, acetone, or garlic, headache, lethargy, weakness, tachypnea, ketosis, ataxia, hypotension, and tachycardia may develop.
   2. SEVERE TOXICITY: Psychosis, hallucinations, ataxia, seizures, extrapyramidal movement disorders, paralysis, encephalopathy, coma, cardiovascular collapse, hypotension, cardiogenic shock, and sensorimotor neuropathy have been reported.
   3. CHRONIC DISULFIRAM TOXICITY: Headache, drowsiness, seizures, neuropathy, and dermatitis. Occasionally implicated in producing psychosis, optic neuritis, and encephalopathy. Hematologic, neuromuscular, and gastrointestinal toxicity and hepatotoxicity may occur 10 days to 12 months after therapy has begun. Toxic or hypersensitivity hepatitis, including death, has been reported. Fatal hepatic necrosis following six weeks of disulfiram therapy (250 mg/day) has also been reported. Effects appear at highly variable time intervals ranging from weeks to years of treatment.

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