Paul F Gavaghan Revised by Frederick K Grittner

DISULFIRAM The registered trademark name for disulfiram is Antabuse—it is the most commonly used medication for the treatment of ALCOHOLISM and the only one of two medications (the other being naltrexone) approved for this use in the United States, as of 2000. It is not intended as a substitute for the counseling alcoholics receive while in treatment; it is meant to be an aid in keeping alcoholics sober, so that they may benefit from counseling. Although disulfiram has been in clinical use since the late 1940s, only since the 1980s has its efficacy been studied by appropriate scientific methodology.

Disulfiram is used to deter drinking by causing an unpleasant reaction if a medicated person drinks ALCOHOL (ethanol). This reaction is called the disulfiram-ethanol reaction (DER); the symptoms include flushing, dizziness, rapid heartbeat, nausea, vomiting, and headache. The DER is of varying severity, and the degree of severity often depends on the dose of disulfiram being taken plus the amount of alcohol that was consumed. A DER can cause hypotension (low blood pressure) and can be so severe that death occurrs, although with adjusted dosage regimens this is very rare.

Disulfiram blocks the action of several of the body's enzymes, including aldehyde dehydrogenase (ALDH). The inhibition of ALDH is responsible for the DER; this occurs because ethanol (drinking alcohol) is metabolized in the liver to acetaldehyde. Acetaldehyde, in turn, is converted to acetic acid, which is catabolized to water and carbon dioxide.

Aldehyde dehydrogenase is the enzyme that facilitates the catabolism of acetaldehyde to acetate acid. When the action of ALDH is inhibited by disulfiram, acetaldehyde is not converted to acetate but accumulates in the blood. Most of the symptoms of the DER are due to the increased circulating acetaldehyde. Since the inhibition of ALDH by disulfiram is irreversible, a person taking disulfiram cannot stop taking it one day and begin drinking the next—several days (usually 4 to 7) must go by, because this is the amount of time necessary for the body to produce new enzyme.

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