Side effects
The most common side effects in the absence of alcohol are headache, and a metallic or garlic taste in the mouth, though more severe side effects may occur. Tryptophol, a chemical compound that induces sleep in humans, is formed in the liver after disulfiram treatment. Less common side effects include decrease in libido, liver problems, skin rash, and nerve inflammation. Liver toxicity is an uncommon but potentially serious side effect, and risk groups e.g. those with already impaired liver function should be monitored closely. That said, the rate of disulfiram-induced hepatitis are estimated to be in between 1 per 25,000 to 1 in 30,000, and rarely the primary cause for treatment cessation. Cases of disulfiram neurotoxicity have also occurred, causing extrapyramidal and other symptoms. Disulfiram can produce neuropathy in daily doses of less than the usually recommended 500 mg. Nerve biopsies showed axonal degeneration and the neuropathy is difficult to distinguish from that associated with ethanol abuse. Disulfiram neuropathy occurs after a variable latent period (mean 5 to 6 months) and progresses steadily. Slow improvement may occur when the drugs use is stopped; often there is complete recovery eventually.Disulfiram disrupts metabolism of several other compounds, including paracetamol (acetaminophen), theophylline and caffeine. However, in most cases, this disruption is mild and presents itself as a 20–40% increase in the half-life of the compound at typical dosages of disulfiram.
Similarly acting substances
In medicine, the term "disulfiram effect" refers to an adverse effect of a particular medication in causing an unpleasant hypersensitivity to alcohol, similar to the effect caused by disulfiram administration.Examples:
Antibiotics (nitroimidazoles), e.g. metronidazole
First-generation sulfonylureas, e.g. tolbutamide and chlorpropamide
Several cephalosporin drugs, including cefoperazone, cefamandole and cefotetan, that have a N-methylthio-tetrazole moiety
Griseofulvin, an oral antifungal drug
Procarbazine
Temposil, or citrated calcium carbimide, has the same function as disulfiram, but is weaker and safer. Coprine, which metabolizes to 1-aminocyclopropanol, a chemical having the same metabolic effects as disulfiram. It occurs naturally in the otherwise edible common ink cap mushroom (Coprinopsis atramentaria), hence its colloquial name "tipplers bane". Similar reactions have been recorded with Clitocybe clavipes and Suillellus luridus, although the agent in those species is unknown. History
The synthesis of disulfiram, originally known as tetraethylthiuram disulfide, was first reported in 1881. By around 1900, it was introduced to the industrial process of sulfur vulcanization of rubber and became widely used. In 1937 a rubber factory doctor in the US published a paper noting that workers exposed to disulfiram had negative reactions to alcohol and could be used as a drug for alcoholism; the effects were also noticed in workers at Swedish rubber boot factory.In the early 1940s it had been tested as a treatment for scabies, a parasitic skin infection, as well as intestinal worms.Around that time, during the German occupation of Denmark, Erik Jacobsen and Jens Hald at the Danish drug company Medicinalco picked up on that research and began exploring the use of disulfiram to treat intestinal parasites.