Disulfiram chemical structure
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Disulfiram

Disulfiram is a drug used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Trade names for disulfiram in different countries are AntabuseĀ® and AntabusĀ®. more...

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Under normal metabolism, alcohol is broken down in the liver by the enzyme alcohol dehydrogenase to acetaldehyde, which is then converted by the enzyme acetaldehyde dehydrogenase to the harmless acetic acid. Disulfiram blocks this reaction at the intermediate stage by blocking the enzyme acetaldehyde dehydrogenase. After alcohol intake under the influence of disulfiram the concentration of acetaldehyde in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. As acetaldehyde is one of the major causes of the symptoms of a "hangover" this produces immediate and severe negative reaction to alcohol intake. Some 5-10 minutes after alcohol intake, the patient may experience the effects of a severe hangover for a period of 30 minutes up to several hours.

Disulfiram should not be taken if alcohol has been consumed in the last 12 hours. There is no tolerance to disulfiram: the longer it is taken, the stronger its effects. As disulfiram is absorbed slowly through the digestive tract and eliminated slowly by the body the effects may last for up to 2 weeks after the initial intake. Clearly, patients must be fully informed about the disulfiram-alcohol reaction.

The drug's action was discovered by accident in the 1940s in the Danish drug company Medicinalco: workers testing the substance, which was intended to treat parasitic diseases, on themselves reported severe symptoms after alcohol consumption.

One weakness with Disulfiram and similar treatments is that if not taken under supervision an alcoholic will often not stick to the treatment, since it is easier to give up the drug than alcohol. Even when strictly taken the negative effects will rarely break the drinking patterns of a chronic alcoholic. In some extreme cases, patients with subcutaneous disulfiram tablet implants have been known to cut or dig out the tablet to avoid its effects. For these reasons disulfiram is not in itself a cure for alcoholism and is usually only indicated for select patients who wish to remain in an enforced state of sobriety during other forms of treatment, such as support groups and psychotherapy.

Similarly acting substances

Coprine, a closely related chemical having the same metabolic effects, occurs naturally in several edible mushroom species, such as the inky cap.

Temposil, or citrated calcium carbamide, has the same function as Antabuse but is weaker and safer.

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Disulfiram, behavior therapy in cocaine dependency
From American Family Physician, 1/1/05 by Karl E. Miller

The use of disulfiram in the treatment of cocaine dependence was first introduced in patients who also were abusing alcohol. Disulfiram was thought to reduce a patient's exposure to alcohol, which could have a positive effect on cocaine exposure. Recent studies examining other medication options for treating cocaine dependency found that disulfiram was an effective treatment even in patients who were not abusing alcohol. This study and others suggest that disulfiram may change the subjective and physiologic response to cocaine, but this treatment has not been studied in the general population of patients dependent on cocaine. Carroll and colleagues evaluated the effectiveness of disulfiram therapy in cocaine-dependent patients. In addition, they evaluated the effectiveness of cognitive-behavior therapy and interpersonal psychotherapy in reducing cocaine use.

The trial was a randomized, placebo-controlled, double-masked study of four treatment strategies. These strategies were disulfiram plus cognitive-behavior therapy, disulfiram plus interpersonal psychotherapy, placebo plus cognitive-behavior therapy, and placebo plus interpersonal psychotherapy. The participants attended a community-based outpatient sub-stance abuse program and met the established criteria for current cocaine dependence. Participants received active medication, disulfiram in a dosage of 250 mg per day, or identical placebo capsules. Participants were advised to avoid alcohol during the study. Follow-up for medication compliance occurred weekly, and adverse events were recorded during this time.Cognitive-behavior therapy and inter-personal psychotherapy were based on an established 12-week program modified for cocaine users. The primary outcome measure was self-reported frequency of cocaine use and urine toxicology results.

There were 121 participants in the study. Medication compliance was 76 percent by self-reporting and 72 percent by laboratory analysis. Participants who received disulfiram were significantly less likely to have a relapse than those taking the placebo. Those in the cognitive-behavior therapy sessions were significantly less likely to have a relapse than participants in the interpersonal psychotherapy sessions. There was no significant difference when the interaction of medication and psychotherapy were compared. Participants who were not alcohol-dependent at the beginning of the study or who abstained from alcohol during the study had a greater benefit from disulfiram and cognitive-behavior therapy. The adverse events in the disulfiram group were not significantly different than those in the placebo group. Those who drank alcohol or used cocaine also reported no more adverse events in the disulfiram group than in the placebo group.

The authors conclude that disulfiram and cognitive-behavior therapy are effective treatment options for patients who are cocaine dependent. They add that disulfiram appears to have a direct effect on cocaine use independent of the patient's alcohol use.

Carroll KM, et al. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients. A randomized placebo-controlled trial. Arch Gen Psychiatry March 2004;61:264-72.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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