Aldehyde Dehydrogenase Inhibitors

ALDEHYDE DEHYDROGENASE INHIBITORS

Disulfiram

It inhibits the enzyme aldehyde dehydrogenase probably after conversion into active metabolites. When alcohol is ingested after taking disulfiram, the concentration of acetaldehyde in tissues and blood rises and a number of highly distressing symptoms (aldehyde syndrome) are produced promptly. These are— flushing, burning sensation, throbbing headache, perspiration, uneasiness, tightness in chest, dizziness, vomiting, visual disturbances, mental confusion, postural fainting and circulatory collapse. Duration of the syndrome (1–4 hours) depends on the amount of alcohol consumed. Because of risk of severe reaction, disulfiram is infrequently used.

Disulfiram has been used as an aversion technique in chronic alcoholics who are motivated and sincerely desire to leave the habit. After abstaining from alcohol overnight, disulfiram is given 1 g on 1st day, 0.75 g on 2nd day, 0.5 g on 3rd and 0.25 g subsequently. Sensitization to alcohol develops after 2–3 hours of first dose, reaches its peak at ~12 hours and lasts for 7–14 days after stopping it, because inhibition of aldehyde dehydrogenase with disulfiram is irreversible: synthesis of fresh enzyme is required for return of activity. Thus, the subject’s resolve not to drink is reinforced by the distressing symptoms that occur if he drinks a little bit. It should not be used in patients who are physically dependent on alcohol.

Side effects of disulfiram (as such) are infrequent, include rashes, metallic taste, nervousness, malaise and abdominal upset. It inhibits a number of other enzymes as well including alcohol dehydrogenase, dopamine β hydroxylase and several cytochrome P450 isoenzymes. Thus, it prolongs t½ of many drugs.

ESPERAL, ANTADICT 250 mg tab. (internationally marketed as ANTABUSE)