Disulfiram-ethyl and methyl alcohol inhibitor and its pharmacology

Description:-

A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.

This compound belongs to the class of organic compounds known as organic thiocarbonic acid derivatives. These are organic compounds containing the thiocarbonic acid structure or a derivative thereof.

Pharmacodynamics:-

Disulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to hereinafter as the disulfiram-alcohol reaction. This reaction, which is proportional to the dosage of both disulfiram and alcohol, will persist as long as alcohol is being metabolized. Disulfiram does not appear to influence the rate of alcohol elimination from the body. Prolonged administration of disulfiram does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol.

Pharmacokinetics:-

Absorption:- Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).

Metabolism:-Hepatic.

Toxicity LD50=8.6g/kg (orally in rats). Symptoms of overdose include irritation, slight drowsiness, unpleasant taste, mild GI disturbances, and orthostatic hypotension.

Drug interaction:-

1. Acenocoumarol+ disulfiram = The serum concentration of Acenocoumarol can be increased when it is combined with Disulfiram.

2. Acetaminophen+ disulfiram = The metabolism of Acetaminophen can be decreased when combined with Disulfiram.

3. Almotriptan+ disulfiram = The metabolism of Almotriptan can be decreased when combined with Disulfiram.

4. Aminophylline+ disulfiram = The serum concentration of Aminophylline can be increased when it is combined with Disulfiram.

5. Amiodarone+ disulfiram = The metabolism of Disulfiram can be decreased when combined with Amiodarone.

6. Amitriptyline+ disulfiram = The metabolism of Amitriptyline can be decreased when combined with Disulfiram.

7. Aniline+ disulfiram = The metabolism of Aniline can be decreased when combined with Disulfiram.

8. Antipyrine + disulfiram = The metabolism of Antipyrine can be decreased when combined with Disulfiram.

9. Aprepitant+ disulfiram = The serum concentration of Disulfiram can be increased when it is combined with Aprepitant.

10. Aripiprazole+ disulfiram = The serum concentration of Aripiprazole can be increased when it is combined with Disulfiram.

Therapeutic Uses:-

This medication is used along with counseling and support to treat alcoholism. Disulfiram works by blocking the processing of alcohol in the body. This causes you to have a bad reaction when you drink alcohol.

Side Effects:-

Drowsiness, tiredness, headache, acne, and metallic/garlic-like taste in the mouth may occur as your body gets used to the medication.

REFERENCE:-Tripathi K D"Essential of medical pharmacology",7th edition ,page no-394