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Disulfiram Type Reaction

disulfiram type reaction

Disulfiram and Disulfiramlike Reactions

Disulfiram tetraethylthiuram disulfide (TETD) was synthesized from thiocarbamide in the 1880s to accelerate the vulcanization (stabilization) of rubber by the addition of sulfur.104 Sixty years later it was the first western medication used to treat alcohol dependence. By the turn of the 20th ­century, most rubber factory workers exposed to disulfiram found that they were intolerant to alcohol.2,32 Williams, a rubber factory occupational physician, wrote, “If the chemical compound disulfiram is not harmful to man, one wonders if one has discovered a cure for alcoholism.” Apart from its use in the rubber industry, beginning in the early 1940s disulfiram was also used in medicine as a scabicide. Two scientists, Hald and Jacobsen, were exploring the antiparasitic effects of disulfiram when they made the rediscovery that ingesting alcohol after loading doses of disulfiram was quite unpleasant.

Metronidazole and alcohol

A 32-year-old man develops diarrhea after receiving amoxicillin/clavulanate to treat an infection following a dog bite. He is diagnosed with Clostridium difficile and prescribed a 10-day course of metronidazole. He has no other medical problems. He will be the best man at his brother’s wedding tomorrow. What advice should you give him about alcohol use at the reception.

Disulfiram-ethanol reaction:

  • 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)

Learn more about Disulfiram

Disulfiram remains the most promising therapeutic agent for cocaine addiction to date. Six randomized controlled trials have now shown the efficacy of disulfiram in treating cocaine addiction [35]. The goal of pharmacological therapy for cocaine is to relieve the craving for dopamine by maintaining stable, elevated levels. Taking cocaine in addition to disulfiram frequently results in a less rewarding, dysphoric response caused by excessive amounts of dopamine.


Disulfiram irreversibly inhibits acetaldehyde dehydrogenase and causes acetaldehyde to accumulate following ingestion of alcohol. Elevated blood acetaldehyde causes facial flushing, severe headache, palpitations, tachycardia, hypertension, respiratory distress, nausea and vomiting. These symptoms commence within 15–30 min of ingesting alcohol and persist for several hours. Tachyarrhythmias, hypotension, collapse and occasional deaths occur if large quantities of alcohol are consumed.

Pharmacologic approach

Disulfiram (Antabuse) is a pharmacologic agent that has been approved by the U.S. Food and Drug Administration (FDA) since 1951 for the treatment of alcoholism.66 Antabuse serves as a deterrent by inducing an unpleasant physical state characterized by nausea or vomiting when alcohol is consumed, thus ideally leading to alcohol cessation.

side effects

Disulfiram has been in use for over 55 years as a ‘psychological threat’ to treat alcoholism because of the severity of the disulfiram-ethanol interaction. When this interaction occurs, blurred vision may be marked, but serious adverse ocular side effects due to disulfiram are uncommon. Retrobulbar and optic neuritis have been well documented by numerous authors. In general, the vision loss secondary to retrobulbar or optic neuritis occurs 1–5 months after disulfiram is discontinued.

These ocular side effects may be more common at higher dosages, in the elderly or in patients with impaired hepatic function. There are a few reports of optic disc hyperemia or optic nerve pallor. Neuropathy elsewhere occurs in 1 in 15 000 patients (Beveilacqua et al 2002) therefore optic nerve disorders are plausible.

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