Antabuse

Antabuse is a substance used in cases of additive disorders (alcohol dependence).

The mechanism of the anti-alcohol effect of the drug is associated with its effect on the metabolism of alcohol inside the body by blocking the activity of enzyme systems that participate in the transformation of alcohol. Along with this, it also blocks the action of 5-oxyindoleacetic acid with adrenaline, causing the accumulation of acetaldehyde in the blood, which leads to the appearance of somatovegetative disorders in a person (potentiation of the heartbeat, decrease in blood pressure, tightness in the chest area, chills, a feeling of horror, etc.).

Indications Antabuse

It is used for therapy in people with chronic alcoholism (any type and phase of the disease).

Release form

It is produced in the form of effervescent tablets of white or almost white color of 200 and 400 mg. There are beveled edges and a score line and the marking "CD" - on one side there are score lines and "C" - on the other side there are score lines.

Pharmacokinetics

Injected into muscle tissue, disulfiram crystallizes at a very high speed, followed by the formation of a large number of small crystals, and then gradually passes into the blood. High lipid solubility rates allow disulfiram to be widely distributed within the body and accumulate within fatty tissues.

Disulfiram undergoes metabolic processes quite quickly with the formation of the element DDC; part of the substance is excreted in the form of carbon disulfide together with the air that the patient exhales, and the other part is involved in intrahepatic metabolism with the formation of methyl-DDC, which is transformed into the therapeutically active component methyl-DTC.

The half-life of methyl-DTC is approximately 10 hours, and its inhibitory effect on aldehyde dehydrogenase is much longer lasting. However, although the metabolic elements are in low concentration, disulfiram-ethanol type manifestations can develop within 20 days from the moment of drug administration.

In case of mild or moderate liver dysfunction, metabolic processes are not weakened. In case of liver cirrhosis, there is an increase in blood levels of metabolites.

Excretion of metabolic elements is mainly realized with urine. Some amount is excreted with air that a person exhales (in the form of carbon disulfide). Another 20% in the form of constant disulfiram is excreted with feces.

Dosing and administration

Before starting therapy, it is necessary to conduct a full examination of the patient. Also, it is necessary to have a conversation with him, in which it should be conveyed that he is strictly forbidden to take drugs or alcoholic beverages during the therapy period. After this, it is necessary to obtain his written consent and a receipt that he was warned about the risks of taking drugs and alcohol, as well as about the obligation to comply with the conditions of a long-term therapeutic and rehabilitation course.

Also, before starting treatment, it is necessary to completely eliminate withdrawal symptoms and complete a course of general strengthening, detoxification and symptomatic treatment. Along with this, it is recommended to perform rational psychotherapy procedures. In addition, 1-3 days before using the drug, you must completely stop using tranquilizers, sleeping pills, neuroleptics and antidepressants. Before starting therapy, the patient must have clinical manifestations of post-withdrawal syndrome: strong psychological craving for drugs and alcohol, bad mood, severe irritability, sleep disorders, anxiety, loss of appetite and fear.

The effervescent tablet is dissolved in water in an amount sufficient to completely dissolve the drug. Treatment is prescribed after a thorough examination of the patient and warning about the consequences and complications. Take 200-500 mg 1-2 times a day according to an individual regimen. After 7-10 days, a disulfiram-alcohol test is performed (20-30 ml of vodka after taking 500 mg of the drug); if the reaction is weak, the alcohol dose is increased by 10-20 ml (the maximum dose of vodka is 100-120 ml). The test is repeated after 1-2 days in hospital and after 3-5 days on an outpatient basis, with adjustment of the alcohol and/or drug doses as needed. Subsequently, a maintenance dose of 150-200 mg/day can be used for 1-3 years.

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Use Antabuse during pregnancy

Antabuse is prohibited during pregnancy. Before starting therapy, it is necessary to completely exclude the possibility of pregnancy in the patient, and use reliable contraceptives during the course.

During the treatment period, you should stop breastfeeding.

Contraindications

Main contraindications:

• severe intolerance associated with disulfiram;
• severe stages of diseases affecting the cardiovascular system: atherosclerosis in the area of the cerebral vessels, severe cardiosclerosis, aortic aneurysm, pre- or post-infarction conditions, elevated blood pressure (grades 2-3), coronary insufficiency, decompensated cardiovascular pathologies and severe diseases affecting the cerebral vessels;
• severe stages of liver failure;
• endocrine diseases, including hyperthyroidism and diabetes (severe or moderate);
• epileptiform syndromes and epilepsy (excluding alcohol-related epilepsy);
• chronic neuropsychiatric pathologies (including manic-depressive psychosis and schizophrenia);
• ulcers in the gastrointestinal tract during the acute stage or with the appearance of bleeding;
• diseases affecting the hematopoietic system;
• neuritis affecting the optic or auditory nerve, as well as polyneuritis;
• glaucoma;
• combination with isoniazid, phenytoin or metronidazole;
• tuberculosis (also diagnosed for the first time; accompanied by infiltrate and hemoptysis);
• having severe or moderate asthma;
• malignant neoplasms;
• leukopenia or anemia;
• pulmonary emphysema and severe respiratory failure;
• endarteritis of an obliterating nature;
• cerebral infections of infectious nature and residual symptoms after a stroke or infection;
• persons over 60 years of age;
• consumption of food or drinks, as well as medications or cosmetics that contain alcohol (within 24 hours from the moment of administration of disulfiram);
• history of psychosis;
• traumatic pathology.

Side effects Antabuse

Side effects include:

• disorders in the functioning of the nervous system: mono- or polyneuropathy, neuritis in the optic nerve area, polyneuritis affecting the legs, drowsiness, disorientation, memory impairment, headaches and disorders of a neuropsychiatric nature are often observed. Sometimes epileptiform seizures develop;
• digestive problems: metallic taste. Sometimes loss of appetite, diarrhea, vomiting, hepatitis or jaundice are observed;
• allergy symptoms: itching or epidermal rash;
• sexual dysfunction: occasional weakening of potency;
• manifestations associated with the disulfiram-ethanol compound: heart rhythm disorders, myocardial infarction, collapse, cerebral edema and angina attacks. In addition, coronary insufficiency with decreased cardiac function, arrhythmic shallow breathing (or its complete cessation), as well as cyanosis in the nails or lips may develop;
• other: sore throat or dry cough, severe fatigue, fear, a sharp medicinal smell from the mouth and severe pain in the injection area with the development of irradiation to the leg, as well as warmth in the throat. Sometimes an increase in temperature to 37-38 ^o C, darkening of the urine and reflex anuria may be observed;
• Changes in test results: Liver function test results may change.

Overdose

In case of intoxication, there is a potentiation of side symptoms, development of encephalopathy or extrapyramidal signs; confusion of consciousness is also observed. In severe disorders, there is a failure of the cardiovascular system function and a comatose state.

Symptomatic actions are carried out. In severe cases, the patient is laid horizontally, with a heating pad at the feet, and is given ammonia to smell and is given vitamin C and glucose intravenously.

If cardiac function is weakened, corazol, cordiamine, caffeine or camphor are used.

In case of a drop in blood pressure, ephedrine, strychnine, adrenaline, as well as metazone and prednisolone are used. Lobeline or cytitone is used subcutaneously; carbogen should also be inhaled.

During epileptiform attacks, 25% magnesium sulfate liquid (5 ml) diluted in 40% glucose (20-40 ml) is administered, as well as 2-4 ml of seduxen. An enema with chlorhydrate is also performed.

Interactions with other drugs

Combining the drug with coumarin anticoagulants (including warfarin) leads to potentiation of anticoagulant activity and increases the likelihood of bleeding.

Disulfiram inhibits the effects of liver enzymes, which is why its use together with substances whose metabolic processes are carried out inside the liver can lead to a disruption of their metabolism.

The combination of the drug and phenothiazine derivatives, tricyclics, and MAOIs may increase the risk of adverse effects associated with drug interactions.

Administration together with buspirone may, in theory, provoke the development of mental disorders (such as mania).

Use with disulfiram reduces the clearance values of imipramine and desipramine.

The combination of Antabuse and amitriptyline can potentiate the medicinal activity of disulfiram, but at the same time the toxic effect of amitriptyline on the central nervous system can be increased.

Administration in combination with chloridazepoxide and diazepam increases their plasma values, which sometimes leads to dizziness. The effect of diazepam can weaken the severity of the effect of disulfiram-alcohol. There is a possibility of potentiation of the toxic properties of temazepam.

Administration together with isoniazid may provoke depression and dizziness; with caffeine - causes a decrease in the rate of excretion of this element from the body; use with metronidazole leads to confusion and the development of psychosis in the active phase; use with omeprazole may cause catatonia and impaired consciousness.

When combining drugs with perphenazine, there is a risk of developing psychotic manifestations.

Use simultaneously with rifampicin causes a slowdown in its metabolic processes and excretion.

The combination of the drug and phenazone prolongs the half-life of the latter.

Use with phenytoin and other benzodiazepine derivatives, as well as with morphine, barbiturates and pentidine potentiates the side effects and therapeutic effects of these medications (due to an increase in their plasma levels); signs of intoxication also appear.

Combination with chlorzoxazone increases its plasma values.

Administration with chlorpromazine may potentiate the decrease in blood pressure.

There is information about the occurrence of drug interactions with substances such as amphetamines and bupropion with methylphenidate.

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Storage conditions

Keep out of reach of children; keep tightly closed in original container; store at room temperature, away from excess heat and moisture (not in the bathroom or near a sink); discard when out of date or no longer needed.

Shelf life

Antabuse can be used for a period of 36 months from the date of manufacture of the pharmaceutical substance.

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Application for children

The drug is prohibited for use in pediatrics.

Analogues

Analogues of the drug are Antakson, Naltrexin, Lidevin with Biotredin, Teturam and Vivitrol with Medichronal and Disulfiram, as well as Esperal, Colme and Naltrex.