The first drug developed to treat alcohol use disorder (AUD), the modern term for alcoholism, was disulfiram (Antabuse). Today disulfiram is still used, but as a second line drug behind acamprosate (Campral) and naltrexone (Revia, Vivitrol). Disulfiram works by blocking the enzymatic breakdown of alcohol and allowing a metabolite to build up in the blood, producing very unpleasant effects. People taking disulfiram will be deterred from ingesting alcohol because they know they will become very ill. The drug is used as an aid to help alcoholics overcome their cravings and addiction.
Disulfiram (a compound that contains sulfur) was first synthesized in 1881 as an industrial chemical, and in the early 1900s was introduced in the manufacturing of rubber. Adding sulfur in rubber manufacturing produces varying degrees of hardness in the final rubber compound.
During the late 1930s sulfur compounds, including disulfiram, were being investigated because of the antimicrobial effects of drugs containing sulfur, and the search was intense. Two scientists at the Danish firm of Medicinalco, Erik Jacobson and Jens Hald, began investigating disulfiram for treatment of intestinal parasites. This company had a group of employees called the “Death Battalion” who would experiment on themselves.
During this phase of testing the drug on themselves, they discovered they became ill after ingesting alcohol. This discovery was made in 1945, but a few years later disulfiram was considered to be used in the treatment of alcoholism as an aversive-reaction drug therapy. Jacobson and Hald’s work was finally published in 1948 and disulfiram was approved by the FDA in 1951.
The discovery of disulfiram led to a renewed interest in the metabolism of alcohol in the body. It was known alcohol was metabolized in the liver and broken down to acetaldehyde then to acetic acid and carbon dioxide by unknown enzymes. In 1950 it was discovered that disulfiram blocked the action of the enzyme that converts acetaldehyde, thus causing an accumulation of acetaldehyde in the bloodstream, which is the cause of the unpleasant effects.
Effects that occur when disulfiram is taken with alcohol include flushing, sweating, nausea and vomiting, chest pain, shortness of breath, and lightheadedness. One should not take disulfiram within 12 hours of alcohol ingestion or 14 days from the last dose of the drug. In addition, products that contain alcohol such as aftershave, cologne, perfume, antiperspirant, and mouthwash can produce unpleasant reactions for people taking Antabuse. Other products to avoid are paint thinners, solvents, and stains, along with dyes, resins and waxes, because even small amounts of alcohol absorbed through the skin can produce the effects.
Other drugs can produce adverse reactions, commonly called the “antabuse-like reaction.” The most notable of these drugs are metronidazole (Flagyl, an antibiotic), griseofulvin (an antifungal), and some cephalosporin antibiotics. If a drug is known to have this side effect, it should be pointed out to the patient by the prescriber and the pharmacist. Always read the drug information given to you when starting a new medication that tells you about side effects that may occur and how to avoid them.
Substance abuse of any kind is not good, but alcohol abuse has been especially devastating to society, families, and individuals because of the convenient availability, relative inexpensiveness, and its association with festivities. In addition, the abuse of alcohol leads to lack of inhibitions and unpredictable behaviors, which are many times violent and destructive. When people take disulfiram, they are acknowledging their problem, and they know that very unpleasant reactions will occur if alcohol is consumed, thus it helps to deter the first drink.
The history of disulfiram is still being written. Currently, it is being studied to treat certain cancers, parasitic infections, HIV, and Covid-19.
Stay informed and stay healthy.
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William Garst is a consultant pharmacist who resides in Alachua, Florida. He received his B.S. in Pharmacy from Auburn University in 1975. He earned a master’s degree in Public Health in 1988 from the University of South Florida and a Master’s in Pharmacy from UF in 2001. In 2007, he received his Doctor of Pharmacy from the University of Colorado. Dr. Garst is a member of many national, state, and local professional associations. He serves on the Alachua County Health Care Advisory Board and stays active as a relief pharmacist. In 2016, he retired from the VA. Dr. Garst enjoys golf, reading (especially history), and family. He writes a blog called The Pharmacy Newsletter (https://thepharmacynewsletter.com/). William Garst can be contacted at communitypharmac
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