A disulfiram-like drug is a drug that causes an adverse reaction to

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

leading to

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

flushing Flushing may refer to: Places * Flushing, Cornwall, a village in the United Kingdom * Flushing, Queens, New York City ** Flushing Bay, a bay off the north shore of Queens ** Flushing Chinatown (法拉盛華埠), a community in Queens ** Flushing ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

, throbbing

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

chest The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the crea ...

and

abdominal discomfort Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a more ...

, and general

hangover A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical sympto ...

-like

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s among others. These effects are caused by accumulation of

acetaldehyde Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...

, a major but toxic

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of alcohol formed by the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to N ...

. The reaction has been variously termed a ''disulfiram-like reaction'', ''alcohol intolerance'', and ''acetaldehyde syndrome''.Mutalik, M., & Sanghavi, D. (2014). ''Review of Drug Interactions: A Comprehensive Update''. The

prototypical drug In pharmacology and pharmaceutics, a prototype drug is an individual drug that represents a drug class – group of medications having similar chemical structures, mechanism of action and mode of action. Prototypes are the most important, and typica ...

of this group is

disulfiram Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of ...

(brand name Antabuse), which acts as an

acetaldehyde dehydrogenase Acetaldehyde dehydrogenases () are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows: Acetaldehyde + NAD+ + Coenzyme A ↔ Acetyl-CoA + NA ...

inhibitor, preventing the metabolism of acetaldehyde into

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...

, and is used in the treatment of

alcoholism Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...

. A variety of other drugs cause disulfiram-like reactions upon consumption of alcohol as unintended

drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...

s and

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s. Many disulfiram-like drugs act as inhibitors of acetaldehyde dehydrogenase similarly to disulfiram. However, some do not act via inhibition of this

, and instead act via other, poorly elucidated mechanisms. Unlike acetaldehyde dehydrogenase inhibitors and other disulfiram-like drugs,

inhibitors such as

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

(brand name Antizol) inhibit the

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

of alcohol into acetaldehyde, thereby increasing and extending the effects of alcohol and reducing its toxicity. As such, they can be thought of as converses of disulfiram-like drugs. Fomepizole is used medically as an

antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

against

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...

and

ethylene glycol Ethylene glycol (IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an odo ...

poisoning A poison can be any substance that is harmful to the body. It can be swallowed, inhaled, injected or absorbed through the skin. Poisoning is the harmful effect that occurs when too much of that substance has been taken. Poisoning is not to ...

List of agents

Intended

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

Calcium carbimide Calcium carbimide, sold as the citrate salt under the trade name Temposil, is a disulfiram-like medication. Its effects are similar to the medication disulfiram (Antabuse) in that it interferes with the normal metabolism of alcohol by preventing ...

Disulfiram Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of ...

* Hydrogen cyanamide

Unintended

Drugs which cause disulfiram-like reactions upon ingestion of alcohol as an unintended effect include: *

Abacavir Abacavir, sold under the brand name Ziagen among others, is a medication used to treat HIV/AIDS. Similar to other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir is used together with other HIV medications, and is not recom ...

Cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...

s such as

cefamandole Cefamandole (INN, also known as cephamandole) 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. Cef ...

cefmenoxime Cefmenoxime is a third-generation cephalosporin antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic ...

cefmetazole Cefmetazole is a cephamycin antibiotic, usually grouped with the second-generation cephalosporins. __TOC__ Adverse effects The chemical structure of cefmetazole, like that of several other cephalosporins, contains an ''N''-methylthiotetrazole ( ...

cefonicid Cefonicide (or cefonicid) is a cephalosporin antibiotic. It has a density of 1.92g/cm3. __TOC__ Synthesis Injectable semi-synthetic cephalosporin antibiotic related to cefamandole, q.v. Cefonicid is synthesized conveniently by nucleophilic dis ...

cefoperazone 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 ...

cefotetan Cefotetan is an injectable antibiotic of the cephamycin type for prophylaxis and treatment of bacterial infections. It is often grouped together with second-generation cephalosporins and has a similar antibacterial spectrum, but with additional ...

ceftriaxone Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint ...

, and latamoxef (moxalactam); thought to be due to common ''N''-methylthiotetrazole

. *

Chloral hydrate Chloral hydrate is a geminal diol with the formula . It is a colorless solid. It has limited use as a sedative and hypnotic pharmaceutical drug. It is also a useful laboratory chemical reagent and precursor. It is derived from chloral (trichl ...

Chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, a ...

Cotrimoxazole Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxaz ...

(

trimethoprim 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 peop ...

/ sulfamethoxazole) *

Ethacrynic acid Etacrynic acid (INN) or ethacrynic acid (USAN), trade name Edecrin, is a loop diuretic used to treat high blood pressure and the swelling caused by diseases like congestive heart failure, liver failure, and kidney failure. A con with etacyrnic ac ...

Griseofulvin Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth. C ...

Hydrazine Hydrazine is an inorganic compound with the chemical formula . It is a simple pnictogen hydride, and is a colourless flammable liquid with an ammonia-like odour. Hydrazine is highly toxic unless handled in solution as, for example, hydrazine ...

s such as

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For l ...

and

procarbazine Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain cancers. For Hodgkin's it is often used together with chlormethine, vincristine, and prednisone while for brain cancers such as glioblastoma multif ...

Ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...

Macrolide The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrol ...

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified in ...

s such as

pimecrolimus Pimecrolimus is an immunomodulating agent of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema). It is available as a topical cream, once marketed by Novartis (however, Galderma has been promoting the compound in ...

and

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

* Mepacrine (quinacrine) *

Nilutamide Nilutamide, sold under the brand names Nilandron and Anandron, is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer.https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020169s008lbl.pdf It has also been ...

* Nitrovasodilators (nitrates) such as

nitroglycerin Nitroglycerin (NG), (alternative spelling of nitroglycerine) also known as trinitroglycerin (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless, oily, explosive liquid most commonly produced by nitrating g ...

Nitroimidazole 5-Nitroimidazole is an organic compound with the formula O2NC3H2N2H. The nitro group at position 5 on the imidazole ring is the most common positional isomer. The term nitroimidazole also refers to a class of antibiotics that share similar chemi ...

s such as

benznidazole Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease this decreases in those who have long-term infection. It is the first-line treatment given its moderate side effe ...

metronidazole 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 ef ...

ornidazole Ornidazole is an antibiotic used to treat protozoan infections. A synthetic nitroimidazole, it is commercially obtained from an acid-catalyzed reaction between 2-methyl-5-nitroimidazole and epichlorohydrin. Antimicrobial spectrum is similar to th ...

, and

tinidazole Tinidazole is a drug 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 ...

Pargyline Pargyline (brand name Eutonyl) is an irreversible selective monoamine oxidase (MAO)-B inhibitor drug ( IC50 for MAO-A is 0.01152 μmol/L and for MAO-B is 0.00820 μmol/L) It was brought to market in the US and the UK by Abbott in 1963 as an ...

Phenacetin Phenacetin (acetophenetidin, ''N''-(4-ethoxyphenyl)acetamide) is a pain-relieving and fever-reducing drug, which was widely used following its introduction in 1887. It was withdrawn from medicinal use as dangerous from the 1970s (e.g., withdrawn ...

Phentolamine Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist. Mechanism Its primary action is vasodilation due to α1 blockade. Non-selective α-blockers can cause a much more pronounced ...

Phenylbutazone Phenylbutazone, often referred to as "bute", is a nonsteroidal anti-inflammatory drug (NSAID) for the short-term treatment of pain and fever in animals. In the United States and United Kingdom, it is no longer approved for human use (except in th ...

Procarbazine Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain cancers. For Hodgkin's it is often used together with chlormethine, vincristine, and prednisone while for brain cancers such as glioblastoma multif ...

Propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...

* Sulfiram *

Sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...

s *

Sulfonylurea Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...

s such as

chlorpropamide Chlorpropamide is a drug in the sulfonylurea class used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea. Mechanism of action Like other sulfonylureas, chlorpropamide acts to increase the secretion of insulin, ...

, glibenclamide (glyburide), and

tolbutamide Tolbutamide is a first-generation potassium channel blocker, sulfonylurea oral hypoglycemic medication. This drug may be used in the management of type 2 diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by ...

Tolazoline Tolazoline is a non-selective competitive α-adrenergic receptor antagonist. It is a vasodilator that is used to treat spasms of peripheral blood vessels (as in acrocyanosis). It has also been used (in conjunction with sodium nitroprusside) ...

Natural

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

Coprine Coprine is a mycotoxin. It was first isolated from common inkcap (''Coprinopsis atramentaria''). It occurs in mushrooms in the genera ''Coprinopsis'' When combined with alcohol, it causes "Coprinus syndrome". It inhibits the enzyme acetaldehyde ...

, via

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

1-aminocyclopropanol; found in

mushroom A mushroom or toadstool is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground, on soil, or on its food source. ''Toadstool'' generally denotes one poisonous to humans. The standard for the name "mushroom" is t ...

s such as ''

Ampulloclitocybe clavipes ''Ampulloclitocybe clavipes'', commonly known as the club-foot or club-footed clitocybe, is a species of gilled mushroom from Europe and North America. The grey brown mushrooms have yellowish decurrent gills and a bulbous stalk, and are found in ...

'' (club-footed clitocybe), '' Coprinus atramentarius'' (common inkcap), and ''

Imperator torosus ''Imperator torosus'', commonly known as the brawny bolete, is a species of bolete fungus in the family Boletaceae. It is native to southern Europe east to the Caucasus and Israel. It is generally associated with deciduous trees such as hornbea ...

'' (brawny bolete) among others *Kudzu (''Pueraria lobata'

*

Coprinopsis atramentaria ''Coprinopsis atramentaria'', commonly known as the common ink cap or inky cap, is an edible (although poisonous when combined with alcohol) mushroom found in Europe and North America. Previously known as ''Coprinus atramentarius'', it is th ...

List of agents previously thought to cause disulfiram-like reactions

Metronidazole 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 ef ...

References

{{Dependence treatment Alcohol Alcohol abuse Alcohol and health Substance-related disorders

List of agents

Intended

Unintended

Natural

List of agents previously thought to cause disulfiram-like reactions

See also

References