Disulfiram-alcohol reaction (DAR) is the effect of the interaction in the human body of alcohol drunk with disulfiram or some mushrooms.[1][2] The DAR is key to disulfiram therapy that is widely used for alcohol-aversive treatment and management of other addictions (e.g. cocaine[3][4] use).[5][6] Once disulfiram-treated patients take alcohol, even in small doses, they experience strong unpleasant sensations (flush, nausea, lightheadedness, headache, sweating, vomiting, and vertigo).[7]
Quick Facts Other names, Specialty ...
Close
Disulfiram has been used to treat alcoholism since 1948 after its accidental discovery in Denmark.[8][9][10]
DAR symptoms usually begin within 5–15 minutes of the ingestion of alcohol by a patient who has taken disulfiram 3–12 hours before.[8]
Increased acetaldehyde content in blood is considered to be the cause of the toxic effect.[11][12] Disulfiram inhibits several human aldehyde dehydrogenases (ALDH),[13] most importantly the version coded for by gene ALDH2 which metabolizes acetaldehyde.[14] The reaction is found to depend on a disulfiram-induced predisposition reflected by alkalosis, the blood acetaldehyde level, and an individual predisposition reflected by dopamine β-hydroxylase activity.[15]
The intensity of a patient's experience of DAR varies with race of the subject.[16]
It has long been known that disulfiram can cause hepatitis and can be fatal (1 case per 30,000 patients), although due to dosage reductions in recent decades, such cases are extremely rare.[17] Death, however, from the reaction itself without significant liver damage is also possible as an atypical case.[18][19]
DAR can occur from skin contact of a disulfiram-treated patient with alcohol-containing skin care products such as colognes, sunscreen lotions, aftershave lotions, and alcohol-based tar gels,[20] but a significant toxic effect does not appear to be achieved in this way.[21] During the COVID-19 pandemic, there were also cases of DAR initiation due to the use of alcohol-based hand sanitizers.[22]
Some mushrooms contain substances that, when combined with alcohol, cause DAR.[23] They include lurid bolete (Boletus luridus),[24] inky cap (Coprinopsis atramentaria),[25][26] and club-foot (Clitocybe clavipes).[27] Because of the similarities to disulfiram (tetraethylthiuram disulfide) poisoning, it was long speculated that disulfiram was the active ingredient in common inkcap. In 1975, coprine was identified as the compound in the common inkcap, with the mechanism identified in 1979.[28][29][30]
Elenbaas, R. M. (August 1977). "Drug therapy reviews: management of the disulfiram-alcohol reaction". American Journal of Hospital Pharmacy. 34 (8): 827–831. PMID 331944. Johansson, Benny; Angelo, Helle R.; Christensen, Jens Knud; Møller, Ib Walther; Rønsted, Per (March 1991). "Dose-Effect Relationship of Disulfiram in Human Volunteers. II: A Study of the Relation between the Disulfiram-Alcohol Reaction and Plasma Concentrations of Acetaldehyde, Diethyldithiocarbamic Acid Methyl Ester, and Erythrocyte Aldehyde Dehydrogenase Activity". Pharmacology & Toxicology. 68 (3): 166–170. doi:10.1111/j.1600-0773.1991.tb01216.x. PMID 1647526. Beyeter, Christine; Fisch, Hans-Ulrich; Preisig, Rudotf (March 1985). "The Disulfiram-Alcohol Reaction: Factors Determining and Potential Tests Predicting Severity". Alcoholism: Clinical and Experimental Research. 9 (2): 118–124. doi:10.1111/j.1530-0277.1985.tb05531.x. PMID 3890590. Tayyareci, Yelda; Acarel, Esra (January 2009). "Acute myocardial infarction associated with disulfiram-alcohol interaction in a young man with normal coronary arteries". Turk Kardiyoloji Dernegi Arsivi. 37 (1): 48–50. PMID 19225254. Amuchastegui, Tomas; Amuchastegui, Marcos; Donohue, Thomas (February 2014). "Disulfiram--alcohol reaction mimicking an acute coronary syndrome". Connecticut Medicine. 78 (2): 81–84. PMID 24741856. Glatt, M. M. (April 1959). "Disulfiram and Citrated Calcium Carbimide in the Treatment of Alcoholism". Journal of Mental Science. 105 (439): 476–481. doi:10.1192/bjp.105.439.476. PMID 13665310. Raby, K. (March 1954). "Relation of blood acetaldehyde level to clinical symptoms in the disulfiram-alcohol reaction". Quarterly Journal of Studies on Alcohol. 15 (1): 21–32. doi:10.15288/qjsa.1954.15.021. PMID 13155779. Wicht, Francis; Fisch, Hans-Ulrich; Nelles, Joachim; Raisin, Juergen; Allemann, Peter; Preisig, Rudolf (April 1995). "Divergence of Ethanol and Acetaldehyde Kinetics and of the Disulfiram-Alcohol Reaction between Subjects with and without Alcoholic Liver Disease". Alcoholism: Clinical and Experimental Research. 19 (2): 356–361. doi:10.1111/j.1530-0277.1995.tb01515.x. PMID 7625569. Sauter, A M; Boss, D; von Wartburg, J P (September 1977). "Reevaluation of the disulfiram-alcohol reaction in man". Journal of Studies on Alcohol. 38 (9): 1680–1695. doi:10.15288/jsa.1977.38.1680. PMID 916687. Amador, Elias; Gazdar, Adi (December 1967). "Sudden Death during Disulfiram—Alcohol Reaction". Quarterly Journal of Studies on Alcohol. 28 (4): 649–654. doi:10.15288/qjsa.1967.28.649. PMID 6082192. Heath, M.J.; Pachar, J.V.; Perez Martinez, A.L.; Toseland, P.A. (September 1992). "An exceptional case of lethal disulfiram-alcohol reaction". Forensic Science International. 56 (1): 45–50. doi:10.1016/0379-0738(92)90145-M. PMID 1398376. Budmiger, H.; Kocher, F. (21 August 1982). "Hexen-Röhrling (Boletus luridus) mit Alkohol. Schweiz. Medizinische Wochenschrift" [Boletus luridus and alcohol. Case report]. Schweizerische Medizinische Wochenschrift (in German). 112 (34): 1179–1181. PMID 7134946. Lash, Erica; Hack, Jason B. (August 2019). "Disulfiram and Hypotension in a 53-year-old Woman". Rhode Island Medical Journal. 102 (6): 44–46. PMID 31398969. Lash, Erica; Hack, Jason B (2019). "Disulfiram and Hypotension in a 53-year-old Woman". Rhode Island Medical Journal (2013). 102 (6): 44–46. PMID 31398969. Lindberg, Per; Bergman, Rolf; Wickberg, Börje (1975). "Isolation and structure of coprine, a novel physiologically active cyclopropanone derivative from Coprinus atramentarius and its synthesis via 1-aminocyclopropanol". Journal of the Chemical Society, Chemical Communications (23): 946–947. doi:10.1039/C39750000946. Lindberg, Per; Bergman, Rolf; Wickberg, Börje (1977). "Isolation and structure of coprine, the in vivo aldehyde dehydrogenase inhibitor in Coprinus atramentarius; syntheses of coprine and related cyclopropanone derivatives". Journal of the Chemical Society, Perkin Transactions 1 (6): 684–691. doi:10.1039/P19770000684. Wiseman, Jeffrey S.; Abeles, Robert H. (May 2002). "Mechanism of inhibition of aldehyde dehydrogenase by cyclopropanone hydrate and the mushroom toxin coprine". Biochemistry. 18 (3): 427–435. doi:10.1021/bi00570a006. PMID 369602.
