Disulfiram-alcohol reaction (DAR) is the effect of the interaction in the human body of alcohol drunk with

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 Enzyme inhibition, inhibiting the enzyme aldehyde dehydrogenase (specifically ALD ...

or some types of mushrooms. The DAR is key to disulfiram therapy that is widely used for alcohol-aversive treatment and management of other addictions (e.g.

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

use). Once disulfiram-treated patients take

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

, even in small doses, they experience strong unpleasant sensations (

flush Flush may refer to: Places * Flush, Kansas, a community in the United States Architecture, construction and manufacturing * Flush cut, a type of cut made with a French flush-cut saw or diagonal pliers * Flush deck, in naval architecture * F ...

, nausea,

lightheadedness Lightheadedness is a common and typically unpleasant sensation of dizziness or a feeling that one may faint. The sensation of lightheadedness can be short-lived, prolonged, or, rarely, recurring. In addition to dizziness, the individual may fee ...

, headache, sweating, vomiting, and

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

). Disulfiram has been used to treat

alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...

since 1948 after its accidental discovery in

Denmark Denmark is a Nordic countries, Nordic country in Northern Europe. It is the metropole and most populous constituent of the Kingdom of Denmark,, . also known as the Danish Realm, a constitutionally unitary state that includes the Autonomous a ...

Pharmacology

DAR symptoms usually begin within 5–15 minutes of the ingestion of alcohol by a patient who has taken

3–12 hours before. Increased

acetaldehyde Acetaldehyde (IUPAC systematic name ethanal) is an organic compound, organic chemical compound with the chemical formula, formula , sometimes abbreviated as . It is a colorless liquid or gas, boiling near room temperature. It is one of the most ...

content in blood is considered to be the cause of the toxic effect. Disulfiram inhibits several human

aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have ...

s (ALDH), most importantly the version coded for by gene

ALDH2 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 majo ...

which metabolizes acetaldehyde. The reaction is found to depend on a disulfiram-induced predisposition reflected by

alkalosis Alkalosis is the result of a process reducing hydrogen ion concentration of arterial blood plasma (alkalemia). In contrast to acidemia (serum pH 7.35 or lower), alkalemia occurs when the serum pH is higher than normal (7.45 or higher). Alkalosis ...

, the blood acetaldehyde level, and an individual predisposition reflected by

dopamine β-hydroxylase Dopamine beta-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme () that in humans is encoded by the DBH gene. Dopamine beta-hydroxylase catalysis, catalyzes the conversion of dopamine to norepinephrine. The three substr ...

activity. The intensity of a patient's experience of DAR varies with the ethnicity of the patient. It has long been known that

can cause

hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...

and can be fatal (1 case per 30,000 patients), although due to dosage reductions in recent decades, such cases are extremely rare. Death, however, from the reaction itself without significant liver damage is also possible as an atypical case.

Unintended initiations

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, but a significant toxic effect does not appear to be achieved in this way. During the

COVID-19 pandemic The COVID-19 pandemic (also known as the coronavirus pandemic and COVID pandemic), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began with an disease outbreak, outbreak of COVID-19 in Wuhan, China, in December ...

, there were also cases of DAR initiation due to the use of alcohol-based

hand sanitizer Hand sanitizer (also known as hand antiseptic, hand disinfectant, hand rub, or handrub) is a liquid, gel, or foam used to kill viruses, bacteria, and other microorganisms on the hands. It can also come in the form of a cream, spray, or wipe. W ...

s. Some mushrooms contain substances that, when combined with alcohol, cause DAR. They include

lurid bolete ''Suillellus luridus'' (formerly ''Boletus luridus''), commonly known as the lurid bolete, is a fungus of the family Boletaceae, found in calcareous broad-leaved tree, broadleaved woodlands in Europe. Basidiocarp, Fruit bodies appear in summer ...

(''Boletus luridus''),

inky cap ''Coprinopsis atramentaria'', commonly known as the common ink cap, tippler's bane, or inky cap, is a species of fungus. Previously known as ''Coprinus atramentarius'', it is the second best-known ink cap and previous member of the genus '' ...

(''Coprinopsis atramentaria''), and club-foot (''Clitocybe clavipes''). Because of the similarities to

(tetraethylthiuram disulfide) poisoning, it was long speculated that disulfiram was the active ingredient in common inkcap. In 1975,

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 aldehyde de ...

was identified as the compound in the common inkcap, with the mechanism identified in 1979.

References

{{Reflist Alcohol and health Substance-related disorders

Pharmacology

Unintended initiations

See also

References