Disulfiram Toxicity Clinical Presentation
- Author: Samara Soghoian, MD, MA; Chief Editor: Asim Tarabar, MD more...
History
The disulfiram-ethanol reaction (DER) is the classic manifestation of patients with disulfiram toxicity. This reaction occurs after the ingestion of even small amounts of ethanol with the concomitant use of disulfiram or disulfiramlike agents. Disulfiram toxicity may also occur in the absence of ethanol exposure. Direct toxic effects are seen with both chronic use and acute massive ingestion.
Ethanol blood levels as low as 5-10 mg/dL can precipitate a disulfiram-ethanol reaction; 120-150 mg/dL can lead to unconsciousness.
- Patients may experience DER signs and symptoms after the ingestion of ethanol-containing foods, medications, and products (eg, over-the-counter cough medications, mouthwash, facial-cleaning products, liquid herbal extracts).
- Some common medications that contain an ethanol concentration greater than 5% include Adult Tylenol liquid, Benadryl Elixir, Comtrex, Donnatal Elixir, Dramamine Liquid, Geritol Liquid, NyQuil Liquid, Formula 44 Cough Mixture, and Tylenol & Codeine Elixir.
- In general, the severity and duration of a reaction depend on the amount of ethanol ingested, the dosage and duration of disulfiram therapy, and individual sensitivity.
- DER symptoms usually occur within 15-30 minutes of ethanol ingestion and last for several hours. Peak effects occur within 8-12 hours.
- DER may occur within 3 hours of a disulfiram dose and up to 2 weeks following discontinuance of disulfiram.
- Lethal DERs have been reported; however, most DER cases are mild and patients recover without serious sequelae.
Obtain a detailed organ-specific history for proper diagnosis and management of disulfiram toxicity due to chronic use or acute massive ingestion.
- Neurologic toxicity increases with dose and duration of therapy and includes the following:
- Central and peripheral sensory motor neuropathy[3]
- Diffuse toxic axonopathy
- Psychosis - Limbic system stimulation by dopamine
- Choreoathetosis - Basal ganglia stimulation by dopamine
- Parkinsonism - Caused by low-density lesions in the basal ganglia
- Catatonia - Occurs more often with chronic toxicity than with acute toxicity
- Movement disorders - From dopamine excess, an enhanced excitotoxic effect of glutamate and calcium-mediated cell death
- Dermatologic toxicity - Peaks at about 2 weeks of treatment; exfoliative dermatitis and allergic dermatitis (may be an unrecognized nickel allergy)
- Gastrointestinal toxicity
- Rotten-egg odor on breath (sulfide metabolites), garliclike or metallic aftertaste in mouth
- Hypersensitive or toxic hepatitis - Peaks at about 2 months of therapy and has a fatality rate of approximately 1 in 25,000 cases
- A retrospective review of the use of disulfiram among alcoholic patients being treated for active tuberculosis with isoniazid-containing regimens found no increased hepatotoxicity in patients taking both disulfiram and isoniazid. However, conclusions from this study are limited due to the retrospective nature and the very small sample size (13 patients) of the study.[4]
- Cholestatic jaundice
- Ophthalmologic toxicity - Optic neuritis (atrophy)
- Hematologic toxicity - Agranulocytosis, eosinophilia, thrombocytopenia, and methemoglobinemia
Physical
Acetaldehyde syndrome may present with the following findings:
- Head, neck, and chest flushing - Histamine-induced vasodilation
- Throbbing headaches
- Nausea, vomiting (may be refractory), diarrhea, and abdominal pain
- Weakness, dizziness, confusion, and anxiety
- Vertigo and ataxia
- Orthostatic hypotension - Hypotensive flushing reaction with warm extremities
- Diaphoresis
- Palpitations and dysrhythmias
- Pruritus
- Refractory cyanosis (eg, methemoglobinemia)
Signs and symptoms of acute disulfiram overdose in adults and children include the following:
- Hypotension, tachycardia, and dyspnea
- Abdominal pain, nausea, vomiting, and sulfur or garlic odor on breath
- Agitation, dysarthria, chorea, hallucinations, and lethargy
- Coma and seizures
- Parkinsonlike syndrome (eg, dystonia, spastic tetraparesis)
- Polyneuropathy
- Hypersensitive hepatitis and hepatic failure
- Loss of developmental milestones
Causes
Agents that may produce disulfiramlike reactions with ethanol include the following:
- Industrial solvents ("degreasers' flush")
- Mushrooms (eg, Coprinus atramentarius [inky cap], Clitocybe claviceps)
- Antibiotics (eg, metronidazole, sulfonamides, some cephalosporins, nitrofurantoin, chloramphenicol)
- Pesticides (eg, carbamates, monosulfiram [Tetmosol])
- Chloral hydrate
- Antifungals (griseofulvin)
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