Disulfiram

Disulfiram is an active substance for the treatment of alcohol dependence. It is a carbamate derivative, i.e. a derivative of carbamates. Disulfiram inhibits the complete breakdown of alcohol. It is a white crystalline (crystal-forming) powder that is not soluble in water. Disulfiram should not be used on its own, but as part of a holistic withdrawal therapy for alcoholics as an accompanying therapy.

Disulfiram is used as an adjunctive therapy for the withdrawal of alcoholics. It is converted in the body to diethyl thiocarbonate, which blocks the enzyme aldehyde dehydrogenase in the liver in a targeted (selective) and irreversible (irreversible) manner. Alcohol is first converted in the body by the enzyme alcohol dehydrogenase to acetaldehyde, a substance that is poisonous (toxic) to the body, and then converted by aldehyde dehydrogenase to acetic acid , which is harmless to the body. The inhibition of aldehyde dehydrogenase by disulfiram does not result in the conversion to the harmless acetic acid, but the poisonous (toxic) acetaldehyde accumulates in the body. Each time the alcoholic ingests alcohol, a series of intolerance reactions occur due to the increase in the concentration of toxic acetaldehyde.

The following reactions are observed:

• heat
• reddening of the skin
• vasodilation
• Low blood pressure (hypotension)
• Rapid pulse (tachycardia)
• strong heartbeat (palpitations)
• headache
• sweating
• Breathing disorders
• rapid breathing (hyperventilation)
• chest pain.

These numerous unpleasant reactions are intended to trigger an aversion to alcohol in those affected (aversion therapy). The effect of these intolerance reactions lasts until the alcohol is completely broken down.

Disulfiram also inhibits the enzyme dopamine β-hydroxylase. This enzyme is responsible for the conversion of dopamine into noradrenaline. This inhibition reduces the likelihood of relapse.

Always take disulfiram exactly as described in the package leaflet or as advised by your doctor.

The recommended dose is 800 mg/day for 2-3 days at the start of treatment.

After 2-3 days, a daily dose of 100-200 mg/day is recommended. The duration of treatment should be at least 6 months, but may possibly last several years. It is recommended to take disulfiram in the presence of a trusted person. Disulfiram should be taken in the evening as it can cause severe drowsiness. Regular blood tests to check liver function are also recommended.

The following side effects may occur:

Very common:

• Confusion,
• Memory and concentration disorders,
• restlessness
• mania
• depression
• headaches
• drowsiness
• fatigue
• Faintness

Frequent:

• Nausea and vomiting
• Diarrhea
• Altered taste sensation
• Bad breath
• Increase in liver enzymes

Occasionally:

• Hypersensitivity
• Swelling of the skin and mucous membranes
• Itching
• Skin rash

Rarely:

• Perceptual disturbances
• Sensory disturbances
• Excitement
• Overconfidence
• Delusions and hallucinations
• Nervous dysfunction
• tremors
• Color vision disorders
• Muscle and joint pain

Very rare:

• Impotence
• Change in sexual desire
• High blood pressure
• Inflammation of the optic nerve
• Seizures
• Gait instability and movement disorders
• Disorders of fine motor skills
• Speech problems
• hepatic coma
• acute liver failure
• massive inflammation of the liver (hepatitis)
• Liver cell damage, which can be fatal in individual cases
• fever
• blistering
• Increase in ketone bodies (acetonemia)
• Increase in cholesterol

Frequency unknown:

• Pain in the upper abdomen

During disulfiram therapy, the intake of alcohol should be avoided at all costs, as otherwise fatal (lethal) complications such as a heart attack (myocardial infarction) or angina pectoris may occur. Intolerance reactions occur from a quantity of 3 g of pure alcohol (ethanol), which corresponds to approx. 75 ml of beer or 32 ml of wine. It should be noted that alcohol is also contained in some medicines and foods (cough syrups, tinctures, chocolates with alcohol content, etc.). In any case, those affected should be prepared to abstain from alcohol.

Interactions may occur if the following medicines are taken at the same time:

Disulfiram can increase the effect of the following medicines:

• Benzodiazepines (sleeping pills and tranquillizers, anti-anxiety medication)
• Phenytoin (medication for epilepsy)
• Clomipramine (mood-enhancing medication)
• Pimozide (medication for mental illnesses)
• Rifampicin and isoniazid (tuberculosis medication)
• Medication to inhibit blood clotting ("blood thinners")
• Metronidazole (medication for infections)
• Theophylline (medication for respiratory diseases)

The following medications increase intolerance reactions:

• Cyanamide
• metronidazole
• tricyclic antidepressants
• MAO inhibitors
• chlorpromazine
• phenothiazine compounds
• antihypertensive drugs (vasodilators, alpha and beta receptor blockers)

Drugs for the treatment of allergies (antihistamines) and diazepam can weaken the intolerance reactions.

Disulfiram should not be taken with aldehyde-containing medications.

Drugs to neutralize stomach acid (antacids) can reduce the absorption of disulfiram.

Disulfiram must not be taken in the following cases:

• if you are allergic to disulfiram
• if you are allergic to nickel, as there is an increased risk of liver inflammation (hepatitis).
• with a low serum albumin and a serum bilirubin value of >25 mmol/L
• in angina pectoris
• in cardiomyopathies
• cardiac arrhythmia
• severe circulatory disorders with particularly low blood pressure (hypotension)
• diabetes mellitus (diabetes mellitus)
• severe liver and kidney dysfunction
• thyroid disorders
• for lung and respiratory diseases
• epilepsy
• for psychoses
• severe personality disorders
• alcohol consumption (during and up to 14 days after the end of therapy)
• in the case of acute alcohol intoxication or residual alcohol in the blood

Disulfiram is not approved for children and adolescents under the age of 18 .

The lowest possible dosage should be administered to patients over 65 years of age.

Disulfiram is not approved for use during pregnancy.

Disulfiram is not approved for breastfeeding because it passes into breast milk.

Disulfiram was used as early as the 19th century to vulcanize rubber in the manufacture of rubber. Coincidentally, it was discovered in 1937 that it caused intolerance to alcoholic beverages among factory workers. Disulfiram was first approved in Switzerland in 1949. Disulfiram has not been approved in Germany since 2013.