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 therapy in alcoholism - Tips from Other Journals
From American Family Physician, 11/1/90

Disulfiram Therapy in Alcoholism Disulfiram has been used for 40 years in the treatment of alcohol dependency dis-orders. The alcohol-aversive potential of disulfiram was first reported in 1937 by an occupational medicine physician who noted that workers who handled disulfiram, which is also an industrial chemical, manifested a distinct illness when they drank alcohol. Use of the drug was introduced into clinical practice on the basis of anecdotal reports, uncontrolled studies and case series.

Wright and Moore review the risks, benefits, indications and efficacy of this alcohol-aversive drug. Disulfiram is an inhibitor of aldehyde dehydrogenase, a necessary enzyme in the metabolism of ethanol. Persons who drink ethanol while taking disulfiram experience a highly unpleasant reaction, consisting of flushing, weakness, nausea and, occasionally, hypotension. Disulfiram will usually produce an aversive reaction to ethanol at a dosage between 250 and 500 mg per day. Cardiac, hepatic and neurologic toxicity can also occur within this dosage range.

Disulfiram is an adjunctive therapy that should be administered only in conjunction with behavioral and psychosocial therapies. The use of disulfiram in alcoholic patients who are not in a comprehensive treatment program will usually not lead to sustained abstinence.

Contraindications to disulfiram use are listed in the table. The drug should never be administered to intoxicated patients. Patients should understand the risks of drinking while taking disulfiram. The physician and patient must agree about the need for clinical supervision and monitoring for efficacy and side effects.

The authors believe that disulfiram may be most effective in reducing an alcoholic patent's ethanol consumption for a short period, such as when the patient is in a program of education, counseling and therapy. Disulfiram has no proven effect on the long-term outcome of alcoholism. (American Journal of Medicine, June 1990, vol. 88, p. 647.)

COPYRIGHT 1990 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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