Disulfram - General Information
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. [PubChem]
Pharmacology of Disulfram
Disulfram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfram 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. Disulfram 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.
Disulfram for patients
Disulfiram appears to decrease the rate at which certain drugs are metabolized and therefore may increase the blood levels and the possibility of clinical toxicity of drugs given concomitantly.
DISULFIRAM SHOULD BE USED WITH CAUTION IN THOSE PATIENTS REVEIVING PHENYTOIN AND ITS CONGENERS. SINCE THE CONCOMITANT ADMINISTRATION OF THESE TWO DRUGS CAN LEAD TO PHENYTOIN INTOXICATION, PRIOR TO ADMINISTERING DISULFIRAM TO A PATIENT ON PHENYTOIN THERAPY, A BASELINE PHENYTOIN SERUM LEVEL SHOULD BE OBTAINED. SUBSEQUENT TO INITIATION OF DISULFIRAM THERAPY. SERUM LEVELS OF PHENYTOIN SHOULD BE DETERMINED ON DIFFERENT DAYS FOR EVIDENCE OF AN INCREASE OR FOR A CONTINUING RISE IN LEVELS. INCREASED PHENYTOIN LEVELS SHOULD BE TREATED WITH APPROPRIATE DOSAGE ADJUSTMENT.
It may be necessary to adjust the dosage of oral anticoagulants upon beginning or stopping disulfiram. since disulfiram may prolong prothrombin time.
Patients taking isoniazid when disulfiram is given should be observed for the appearance of unsteady gait or marked changes in mental status; the disulfiram should be discontinued if such signs appear.
In rats, simultaneous ingestion of disulfiram and nitrite in the diet for 78 weeks has been reported to cause tumors, and it has been suggested that disulfiram may react with nitrites in the rat stomach to form a nitrosamine, which is tumorigenic. Disulfiram alone in the ratís diet did not lead to such tumors. The relevance of this finding to humans is not known at this time.
Patients who are receiving or have recently received metronidazole. paraldehyde. alcohol, or alcohol-containing preparations, e.g. cough syrups, tonics and the like, should not be given disulfiram.
Disulfiram is contraindicated in the presence of severe myocardial disease or coronary occlusion, psychoses, and hypersensitivity to disulfiram or to other thiuram derivatives used in pesticides and rubber vulcanization.
Additional information about Disulfram
Disulfram Indication: For the treatment and management of chronic alcoholism
Mechanism Of Action: Disulfram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake causing an accumulation of acetaldehyde in the blood producing highly unpleasant symptoms. Disulfram blocks the oxidation of alcohol through its irreversible inactivation of aldehyde dehydrogenase, which acts in the second step of ethanol utilization. In addition, disulfiram competitively binds and inhibits the peripheral benzodiazepine receptor, which may indicate some value in the treatment of the symptoms of alcohol withdrawal, however this activity has not been extensively studied.
Drug Interactions: Aminophylline Increases the effect and toxicity of theophylline
Amprenavir Increased risk of side effects (oral solution)
Anisindione Increases the anticoagulant effect
Chlorzoxazone Increases chlorzoxazone levels
Cocaine Increases the cardiac toxicity of cocaine
Dicumarol Increases the anticoagulant effect
Dyphylline Increases the effect and toxicity of theophylline
Ethotoin Increases the effect of phenytoin
Fosphenytoin Increases the effect of phenytoin
Isoniazid Increased risk of CNS adverse efects
Mephenytoin Increases the effect of phenytoin
Metronidazole Possible acute psychosis and confusion
Oxtriphylline Increases the effect and toxicity of theophylline
Phenytoin Increases the effect of phenytoin
Theophylline Increases the effect and toxicity of theophylline
Warfarin Increases the anticoagulant effect
Acenocoumarol Disulfram increases the anticoagulant effect
Food Interactions: Take without regard to meals.
Avoid alcohol for up to 14 days after treatment has been stopped.
Generic Name: Disulfiram
Synonyms: Dupon 4472; Dupont Fungicide 4472; Disulfuram; Disulphuram; TATD; TETD; Tetraethylthioperoxydicarbonic Diamide; Tetraethylthiram Disulfide; Tetraethylthiram Disulphide; Tetraethylthiuram; Tetraethylthiuram Disulfide; Tetraethylthiuram Disulphide; Tetraethylthiuram Sulfide; Tetraethylthiuran Disulfide; TTD; Usaf B-33
Drug Category: Alcohol Deterrents; Enzyme Inhibitors
Drug Type: Small Molecule; Approved
Absorption: Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).
Toxicity (Overdose): LD50=8.6g/kg (orally in rats). Symptoms of overdose include irritation, slight drowsiness, unpleasant taste, mild GI disturbances, and orthostatic hypotension.
Protein Binding: Not Available
Half Life: Not Available
Dosage Forms of Disulfram: Tablet Oral
Chemical IUPAC Name: diethylcarbamothioylsulfanyl diethylaminomethanedithioate
Chemical Formula: C10H20N2S4
Disulfiram on Wikipedia: https://en.wikipedia.org/wiki/Disulfiram
Organisms Affected: Humans and other mammals