Alcoholsensitizing Agents

The most commonly used alcohol-sensitizing agent is disulfiram, which has been used in clinical practice since the 1950s to deter alcoholics from drinking. It is not an aversive drug in the strict sense of the word, since it is not used, as apomor-phine is used, to condition individuals to have an aversive response at the sight or smell of alcohol. Rather, its objective is to deter drinking by the threat of having a very unpleasant reaction if one does drink alcoholic beverages. Its severity depends on the amount of alcohol and disulfiram in the blood. The symptoms of the reaction include facial flushing, tachycardia (rapid heart beat), palpitations, dyspnea (indigestion), hypotension (lowered blood pressure), headaches, nausea, and vomiting. Deaths have occurred with severe disulfiram— ethanol reactions (DERs).

A DER results when alcohol is ingested because disulfiram inhibits the functioning of an enzyme, aldehyde dehydrogenase. This enzyme is needed to convert the acetaldehyde—the first metabolic product in the catabolism of ethanol—to acetic acid. If aldehyde dehydrogenase is inhibited, an elevation in blood acetaldehyde results. The increased circulating acetaldehyde is believed to cause most of the symptoms and signs of the DER.

Disulfiram is given orally. The usual dose is 250 milligrams, although larger doses have been used. Doses of less than 250 milligrams may fail to cause a DER, while doses of more than 250 milligrams have a greater risk of producing serious side effects. Adverse effects of disulfiram range from mild symptoms such as sedation, lethargy, and a garliclike or metallic taste in the mouth to more serious side effects such as major depression, psychotic reaction, or idiosyncratic toxic hepatitis—which may be fatal. A dose between 250 milligrams and 500 milligrams is usually adequate to cause a DER if alcohol is ingested but not so high as to cause major side effects. The dose should be individualized for each patient.

Alcohol-sensitizing agents other than disulfiram also exist. Calcium carbimide, which is available in Canada under the brand name Temposil, has been used clinically, although it is currently not ap proved by the FDA for use in the United States. Calcium carbimide produces physiological reactions with alcohol similar to those produced by disulfiram, but the onset of action is quick—within one hour after administration—compared to twelve with disulfiram. Also, the duration of action is short—approximately twenty-four hours— versus up to six days with disulfiram. Calcium carbimide, with its faster onset of action, might be especially helpful with impulsive drinkers. A possible side effect of calcium carbimide is reduced thyroid function, however, thus making its use problematic in patients with thyroid problems. It has some additional side effects that include dizziness, slight depression, skin rashes, and impotence. One puzzling side effect of calcium carbimide is a mild elevation in the patient s white blood cell count. As of 2000, there is a paucity of randomized clinical trials comparing calcium carbamide to placebo—so, its efficacy is uncertain.

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