Disulfiram-alcohol reaction

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Disulfiram-alcohol reaction (DAR)
Other namesDisulfiram ethanol reaction (DER), Antabuse effect, Acetylhyde sindrome
The Alcohol Flushing Response.png
Alcohol flush reaction is a visible effect of DAR.
Specialty Toxicology
Symptoms Flush, nausea, lightheadedness, headache, sweating, vomiting, vertigo, etc
CausesIngestion of disulfiram with alcohol

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]

Contents

Disulfiram has been used to treat alcoholism since 1948 after its accidental discovery in Denmark. [8] [9] [10]

Pharmacology

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]

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, [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]

See also

Related Research Articles

A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as forward reactions, and in some cases this has physiological significance: for example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde.

Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3CHO, 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">Alcohol dehydrogenase</span> Group of dehydrogenase enzymes

Alcohol dehydrogenases (ADH) (EC 1.1.1.1) 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 NADH. In humans and many other animals, they serve to break down alcohols that are otherwise toxic, and they also participate in the generation of useful aldehyde, ketone, or alcohol groups during the biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.

<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">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">Mushroom poisoning</span> Harmful effects from ingestion of toxic substances present in a mushroom

Mushroom poisoning is poisoning resulting from the ingestion of mushrooms that contain toxic substances. Symptoms can vary from slight gastrointestinal discomfort to death in about 10 days. Mushroom toxins are secondary metabolites produced by the fungus.

<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">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">Alcohol tolerance</span> Bodily responses to the functional effects of ethanol in alcoholic beverages

Alcohol tolerance refers to the bodily responses to the functional effects of ethanol in alcoholic beverages. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcohol use disorder.

<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.

Ethanol, an alcohol found in nature and in alcoholic drinks, is metabolized through a complex catabolic metabolic pathway. In humans, several enzymes are involved in processing ethanol first into acetaldehyde and further into acetic acid and acetyl-CoA. Once acetyl-CoA is formed, it becomes a substrate for the citric acid cycle ultimately producing cellular energy and releasing water and carbon dioxide. Due to differences in enzyme presence and availability, human adults and fetuses process ethanol through different pathways. Gene variation in these enzymes can lead to variation in catalytic efficiency between individuals. The liver is the major organ that metabolizes ethanol due to its high concentration of these enzymes.

<i>Coprinopsis atramentaria</i> Species of fungus

Coprinopsis atramentaria, commonly known as the common ink cap, tippler's bane, or inky cap, is an edible mushroom found in Europe and North America. Previously known as Coprinus atramentarius, it is the second best known ink cap and previous member of the genus Coprinus after C. comatus. It is a widespread and common fungus found throughout the northern hemisphere. Clumps of mushrooms arise after rain from spring to autumn, commonly in urban and disturbed habitats such as vacant lots and lawns, as well as grassy areas. The grey-brown cap is initially bell-shaped before opening, after which it flattens and disintegrates. The flesh is thin and the taste mild. It can be eaten, but due to the presence of coprine within the mushroom, it is poisonous when consumed with alcohol, as it heightens the body's sensitivity to ethanol in a similar manner to the anti-alcoholism drug disulfiram.

<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">Cyclopropanone</span> Chemical compound

Cyclopropanone is an organic compound with molecular formula (CH2)2CO consisting of a cyclopropane carbon framework with a ketone functional group. The parent compound is labile, being highly sensitive toward even weak nucleophiles. Surrogates of cyclopropanone include the ketals.

<span class="mw-page-title-main">Hangover</span> Discomfort following alcohol consumption

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 symptoms of a hangover may include headache, drowsiness, concentration problems, dry mouth, dizziness, fatigue, gastrointestinal distress, absence of hunger, light sensitivity, depression, sweating, hyper-excitability, irritability, and anxiety.

<span class="mw-page-title-main">Short-term effects of alcohol consumption</span> Overview of the short-term effects of the consumption of alcoholic beverages

The short-term effects of alcohol consumption range from a decrease in anxiety and motor skills and euphoria at lower doses to intoxication (drunkenness), to stupor, unconsciousness, anterograde amnesia, and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once it is in the bloodstream, it can diffuse into nearly every cell in the body.

<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 (drug)</span> Active ingredient in alcoholic beverages

Alcohol, sometimes referred to by the chemical name ethanol, is a depressant drug that is the active ingredient in fermented drinks such as beer, wine, and distilled spirits. It is one of the oldest and most commonly consumed recreational drugs, causing the characteristic effects of alcohol intoxication ("drunkenness"). Among other effects, alcohol produces happiness and euphoria, decreased anxiety, increased sociability, sedation, impairment of cognitive, memory, motor, and sensory function, and generalized depression of central nervous system (CNS) function.

<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-like drug</span> Drug that causes an adverse reaction to alcohol

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. 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.

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