Disulfiram-like drug explained

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Synonyms:Alcohol sensitizers; Alcohol-sensitizing agents; Alcohol-deterrent drugs; Acetaldehyde dehydrogenase inhibitors
Use:Alcoholism
Biological Target:Acetaldehyde dehydrogenase, others

A disulfiram-like drug is a drug that causes an adverse reaction to alcohol leading to nausea, vomiting, flushing, dizziness, throbbing headache, chest and abdominal discomfort, and general hangover-like symptoms among others.[1] These effects are caused by accumulation of acetaldehyde, a major but toxic metabolite of alcohol formed by the enzyme alcohol dehydrogenase. The reaction has been variously termed a disulfiram-like reaction, alcohol intolerance, and acetaldehyde syndrome.[2]

The prototypical drug of this group is disulfiram (brand name Antabuse), which acts as an acetaldehyde dehydrogenase inhibitor, preventing the metabolism of acetaldehyde into acetic acid, and is used in the treatment of alcoholism. A variety of other drugs cause disulfiram-like reactions upon consumption of alcohol as unintended drug interactions and side effects. Many disulfiram-like drugs act as inhibitors of acetaldehyde dehydrogenase similarly to disulfiram. However, some do not act via inhibition of this enzyme, and instead act via other, poorly elucidated mechanisms.

Unlike acetaldehyde dehydrogenase inhibitors and other disulfiram-like drugs, alcohol dehydrogenase inhibitors such as fomepizole (brand name Antizol) inhibit the metabolism of alcohol into acetaldehyde, thereby increasing and extending the effects of alcohol and reducing its toxicity.[3] As such, they can be thought of as converses of disulfiram-like drugs. Fomepizole is used medically as an antidote against methanol and ethylene glycol poisoning.

List of agents

Intended

Drugs which cause disulfiram-like reactions upon ingestion of alcohol as an intended effect include:[4]

Unintended

Drugs which cause disulfiram-like reactions upon ingestion of alcohol as an unintended effect include:[5] [6] [7]

A number of drugs do not cause disulfiram-like reactions, but have other unintended interactions with alcoholic drinks. For example, alcohol interferes with the efficacy of erythromycin. Patients on linezolid and tedizolid may be sensitive to the tyramine present in tap beers and red wine.[8]

Antibiotics

Antibiotics such as metronidazole, tinidazole, cephamandole, latamoxef, cefoperazone, cefmenoxime, and furazolidone, cause a disulfiram-like chemical reaction with alcohol by inhibiting its breakdown by acetaldehyde dehydrogenase, which may result in vomiting, nausea, and shortness of breath.[11] In addition, the efficacy of doxycycline and erythromycin succinate may be reduced by alcohol consumption.[12] Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound.[13]

Natural

Natural compounds and species which have been found to cause disulfiram-like reactions upon ingestion of alcohol include:[14] [15]

List of agents previously thought to cause disulfiram-like reactions

See also

Notes and References

  1. Fraser AG . Pharmacokinetic interactions between alcohol and other drugs . Clin Pharmacokinet . 33 . 2 . 79–90 . 1997 . 9260032 . 10.2165/00003088-199733020-00001 . 45547473 .
  2. Mutalik, M., & Sanghavi, D. (2014). Review of Drug Interactions: A Comprehensive Update.
  3. McMartin K, Jacobsen D, Hovda KE . Antidotes for poisoning by alcohols that form toxic metabolites . Br J Clin Pharmacol . 81 . 3 . 505–15 . 2016 . 26551875 . 4767193 . 10.1111/bcp.12824 .
  4. Book: Helmut K. Seitz. B. Kommerell. Alcohol Related Diseases in Gastroenterology. 6 December 2012. Springer Science & Business Media. 978-3-642-70048-4. 175–.
  5. Book: Amitava Dasgupta. Alcohol, Drugs, Genes and the Clinical Laboratory: An Overview for Healthcare and Safety Professionals. 17 October 2016. Elsevier Science. 978-0-12-809334-4. 77–.
  6. Book: John Marx. Ron Walls. Robert Hockberger. Rosen's Emergency Medicine - Concepts and Clinical Practice E-Book. 1 August 2013. Elsevier Health Sciences. 978-1-4557-4987-4. 2398–.
  7. Book: Reginald Smart. Research Advances in Alcohol and Drug Problems. 22 November 2013. Springer Science & Business Media. 978-1-4613-3626-6. 399–.
  8. Mergenhagen . Kari A. . Wattengel . Bethany A. . Skelly . Megan K. . Clark . Collin M. . Russo . Thomas A. . Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions . Antimicrobial Agents and Chemotherapy . 21 February 2020 . 64 . 3 . 10.1128/aac.02167-19. 7038249 .
  9. Kitson TM . The effect of cephalosporin antibiotics on alcohol metabolism: a review . Alcohol . 4 . 3 . 143–8 . 1987 . 3593530 . 10.1016/0741-8329(87)90035-8.
  10. Book: Lewis R. Goldfrank. Goldfrank's Toxicologic Emergencies. 2006. McGraw Hill Professional. 978-0-07-147914-1.
  11. Web site: Can I drink alcohol while taking antibiotics? . 17 February 2008 . NHS Direct (UK electronic health service) . https://web.archive.org/web/20101024155841/http://www.nhs.uk/chq/pages/871.aspx . 24 October 2010 . live .
  12. Book: Stockley IH . 2002 . Stockley's Drug Interactions . 6th . London . Pharmaceutical Press.
  13. Web site: Antibiotics FAQ . 17 February 2008 . McGill University, Canada . https://web.archive.org/web/20080216195750/http://www.mcgill.ca/studenthealth/information/generalhealth/antibiotics/. 16 February 2008.
  14. Book: Joseph F. Ammirati. Poisonous Mushrooms of the Northern United States and Canada. 1985. U of Minnesota Press. 978-0-8166-1407-3. 131–.
  15. Book: Barry H. Rumack. David G. Spoerke. Handbook of Mushroom Poisoning: Diagnosis and Treatment. 27 September 1994. CRC Press. 978-0-8493-0194-0. 303–.
  16. Web site: Herbal Approaches to Alcohol Dependence: Evidence and Risks . Pharmacy Times . en . 7 December 2016.
  17. 70. 4. 1–187. Workowski. Kimberly A. Bachmann. Laura H. Chan. Philip A. Johnston. Christine M. Muzny. Christina A. Park. Ina. Reno. Hilary. Zenilman. Jonathan M. Bolan. Gail A. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR. Recommendations and Reports . 2021. 10.15585/mmwr.rr7004a1. 34292926. 8344968.
  18. 10.4045/tidsskr.14.0081. 0029-2001. Fjeld. Hilde. Raknes. Guttorm. Er det virkelig farlig å kombinere metronidazol og alkohol?. Tidsskrift for den Norske Legeforening. 22 February 2022. 16 September 2014. 134. 17. 1661–1663. 25223673. free.

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