Disulfiram-like drug

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Disulfiram-like drug
Drug class
Disulfiram2.svg
Disulfiram, the prototypical drug of this class.
Class identifiers
Synonyms Alcohol sensitizers; Alcohol-sensitizing agents; Alcohol-deterrent drugs; Acetaldehyde dehydrogenase inhibitors
Use Alcoholism
Biological target Acetaldehyde dehydrogenase, others
Legal status
In Wikidata

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] [2] These effects are caused by accumulation of acetaldehyde, a major but toxic metabolite of alcohol formed by the enzyme alcohol dehydrogenase. [1] [2] The reaction has been variously termed a disulfiram-like reaction , alcohol intolerance, and acetaldehyde syndrome. [3]

Contents

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. [1] [2] A variety of other drugs cause disulfiram-like reactions upon consumption of alcohol as unintended drug interactions and side effects. [1] [2] 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. [4] As such, they can be thought of as converses of disulfiram-like drugs. [4] Fomepizole is used medically as an antidote against methanol and ethylene glycol poisoning. [4]

List of agents

Intended

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

Unintended

Drugs which cause disulfiram-like reactions upon ingestion of alcohol as an unintended effect include: [6] [1] [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

Related Research Articles

Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated as MeCHO. It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.

<span class="mw-page-title-main">Trimethoprim</span> Antibiotic

Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS. It is taken orally.

This is the timeline of modern antimicrobial (anti-infective) therapy. The years show when a given drug was released onto the pharmaceutical market. This is not a timeline of the development of the antibiotics themselves.

<span class="mw-page-title-main">Disulfiram</span> Chemical compound

Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol. Disulfiram works by inhibiting the enzyme aldehyde dehydrogenase, causing many of the effects of a hangover to be felt immediately following alcohol consumption. Disulfiram plus alcohol, even small amounts, produces flushing, throbbing in the head and neck, a throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, fast heart rate, low blood pressure, fainting, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, abnormal heart rhythms, heart attack, acute congestive heart failure, unconsciousness, convulsions, and death.

<span class="mw-page-title-main">Metronidazole</span> Antibiotic and antiprotozoal medication

Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis. It is an option for a first episode of mild-to-moderate Clostridioides difficile colitis if vancomycin or fidaxomicin is unavailable. Metronidazole is available orally, as a cream or gel, and by slow intravenous infusion.

<span class="mw-page-title-main">Acetaldehyde dehydrogenase</span> Class of enzymes

Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetyl-CoA. This can be summarized as follows:

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

ATC code J01Antibacterials for systemic use is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup J01 is part of the anatomical group J Antiinfectives for systemic use.

<span class="mw-page-title-main">Alcohol flush reaction</span> Effect of alcohol consumption on the human body

Alcohol flush reaction is a condition in which a person develops flushes or blotches associated with erythema on the face, neck, shoulders, ears, and in some cases, the entire body after consuming alcoholic beverages. The reaction is the result of an accumulation of acetaldehyde, a metabolic byproduct of the catabolic metabolism of alcohol, and is caused by an aldehyde dehydrogenase 2 deficiency.

<span class="mw-page-title-main">Tinidazole</span> Chemical compound

Tinidazole, sold under the brand name Tindamax among others, is a medication used against protozoan infections. It is widely known throughout Europe and the developing world as a treatment for a variety of anaerobic amoebic and bacterial infections. It was developed in 1972 and is a prominent member of the nitroimidazole antibiotic class.

<span class="mw-page-title-main">Fomepizole</span> Medication

Fomepizole, also known as 4-methylpyrazole, is a medication used to treat methanol and ethylene glycol poisoning. It may be used alone or together with hemodialysis. It is given by injection into a vein.

<span class="mw-page-title-main">Aldehyde dehydrogenase</span> Group of enzymes

Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes to carboxylic acids. The oxygen comes from a water molecule. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes.

<span class="mw-page-title-main">ALDH2</span> Enzyme

Aldehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH2 gene located on chromosome 12. ALDH2 belongs to the aldehyde dehydrogenase family of enzymes. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. ALDH2 has a low Km for acetaldehyde, and is localized in mitochondrial matrix. The other liver isozyme, ALDH1, localizes to the cytosol.

<span class="mw-page-title-main">Cefoperazone</span> Antibiotic

Cefoperazone is a third-generation cephalosporin antibiotic, marketed by Pfizer under the name Cefobid. It is one of few cephalosporin antibiotics effective in treating Pseudomonas bacterial infections which are otherwise resistant to these antibiotics.

<span class="mw-page-title-main">Cefmetazole</span> Chemical compound

Cefmetazole is a cephamycin antibiotic, usually grouped with the second-generation cephalosporins.

<span class="mw-page-title-main">Cefamandole</span> Chemical compound

Cefamandole is a second-generation broad-spectrum cephalosporin antibiotic. The clinically used form of cefamandole is the formate ester cefamandole nafate, a prodrug which is administered parenterally. Cefamandole is no longer available in the United States.

<span class="mw-page-title-main">Coprine</span> Chemical compound

Coprine is a mycotoxin. It was first isolated from common inkcap. It occurs in mushrooms in the genera Coprinopsis. When combined with alcohol, it causes "Coprinus syndrome". It inhibits the enzyme acetaldehyde dehydrogenase, which is involved in the metabolism of alcohol. This inhibition leads to a buildup of acetaldehyde, causing an alcohol flush reaction. Because of this, the mushroom is commonly referred to as Tippler's Bane.

<span class="mw-page-title-main">Alcohol intolerance</span> Medical condition

Alcohol intolerance is due to a genetic polymorphism of the aldehyde dehydrogenase enzyme, which is responsible for the metabolism of acetaldehyde. This polymorphism is most often reported in patients of East Asian descent. Alcohol intolerance may also be an associated side effect of certain drugs such as disulfiram, metronidazole, or nilutamide. Skin flushing and nasal congestion are the most common symptoms of intolerance after alcohol ingestion. It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome. Severe pain after drinking alcohol may indicate a more serious underlying condition.

<span class="mw-page-title-main">Disulfiram-alcohol reaction</span> Medical condition

Disulfiram-alcohol reaction (DAR) is the effect of the interaction in the human body of alcohol drunk with disulfiram or some mushrooms. The DAR is key to disulfiram therapy that is widely used for alcohol-aversive treatment and management of other addictions. Once disulfiram-treated patients take alcohol, even in small doses, they experience strong unpleasant sensations.

Anti-ulcer agents are medications or supplements used to cure the damage of mucosal layer on organs to prevent the damage from further extending to deeper regions to cause complications.

References

  1. 1 2 3 4 5 John Marx; Ron Walls; Robert Hockberger (1 August 2013). Rosen's Emergency Medicine - Concepts and Clinical Practice E-Book. Elsevier Health Sciences. pp. 2398–. ISBN   978-1-4557-4987-4.
  2. 1 2 3 4 Fraser AG (1997). "Pharmacokinetic interactions between alcohol and other drugs". Clin Pharmacokinet. 33 (2): 79–90. doi:10.2165/00003088-199733020-00001. PMID   9260032. S2CID   45547473.
  3. ↑ Mutalik, M., & Sanghavi, D. (2014). Review of Drug Interactions: A Comprehensive Update.
  4. 1 2 3 McMartin K, Jacobsen D, Hovda KE (2016). "Antidotes for poisoning by alcohols that form toxic metabolites". Br J Clin Pharmacol. 81 (3): 505–15. doi:10.1111/bcp.12824. PMC   4767193 . PMID   26551875.
  5. ↑ Helmut K. Seitz; B. Kommerell (6 December 2012). Alcohol Related Diseases in Gastroenterology. Springer Science & Business Media. pp. 175–. ISBN   978-3-642-70048-4.
  6. ↑ Amitava Dasgupta (17 October 2016). Alcohol, Drugs, Genes and the Clinical Laboratory: An Overview for Healthcare and Safety Professionals. Elsevier Science. pp. 77–. ISBN   978-0-12-809334-4.
  7. ↑ Reginald Smart (22 November 2013). Research Advances in Alcohol and Drug Problems. Springer Science & Business Media. pp. 399–. ISBN   978-1-4613-3626-6.
  8. 1 2 3 4 5 6 7 8 9 10 11 Mergenhagen, Kari A.; Wattengel, Bethany A.; Skelly, Megan K.; Clark, Collin M.; Russo, Thomas A. (21 February 2020). "Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions". Antimicrobial Agents and Chemotherapy. 64 (3). doi:10.1128/aac.02167-19. PMC   7038249 .
  9. ↑ Kitson TM (1987). "The effect of cephalosporin antibiotics on alcohol metabolism: a review". Alcohol. 4 (3): 143–8. doi:10.1016/0741-8329(87)90035-8. PMID   3593530.
  10. ↑ Lewis R. Goldfrank (2006). Goldfrank's Toxicologic Emergencies. McGraw Hill Professional. ISBN   978-0-07-147914-1.
  11. ↑ "Can I drink alcohol while taking antibiotics?". NHS Direct (UK electronic health service). Archived from the original on 24 October 2010. Retrieved 17 February 2008.
  12. ↑ Stockley IH (2002). Stockley's Drug Interactions (6th ed.). London: Pharmaceutical Press.[ page needed ]
  13. ↑ "Antibiotics FAQ". McGill University, Canada. Archived from the original on 16 February 2008. Retrieved 17 February 2008.
  14. ↑ Joseph F. Ammirati (1985). Poisonous Mushrooms of the Northern United States and Canada. U of Minnesota Press. pp. 131–. ISBN   978-0-8166-1407-3.
  15. ↑ Barry H. Rumack; David G. Spoerke (27 September 1994). Handbook of Mushroom Poisoning: Diagnosis and Treatment. CRC Press. pp. 303–. ISBN   978-0-8493-0194-0.
  16. ↑ "Herbal Approaches to Alcohol Dependence: Evidence and Risks". Pharmacy Times. 7 December 2016.
  17. ↑ 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 (2021). "Sexually Transmitted Infections Treatment Guidelines, 2021". MMWR. Recommendations and Reports. 70 (4): 1–187. doi:10.15585/mmwr.rr7004a1. PMC   8344968 . PMID   34292926.
  18. ↑ Fjeld, Hilde; Raknes, Guttorm (16 September 2014). "Er det virkelig farlig å kombinere metronidazol og alkohol?". Tidsskrift for den Norske Legeforening. 134 (17): 1661–1663. doi: 10.4045/tidsskr.14.0081 . ISSN   0029-2001. PMID   25223673 . Retrieved 22 February 2022.
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