disulfiram

Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme aldehyde dehydrogenase (specifically ALDH2), causing many of the effects of a hangover to be felt immediately following alcohol consumption. Disulfiram plus alcohol, even small amounts, produces flushing, throbbing in the head and neck, a throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, shortness of breath, hyperventilation, fast heart rate, low blood pressure, fainting, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, abnormal heart rhythms, heart attack, acute congestive heart failure, unconsciousness, convulsions, and death.

In the body, alcohol is converted to acetaldehyde, which is then broken down by ALDH2. When the dehydrogenase enzyme is inhibited, acetaldehyde builds up, causing unpleasant side effects. The clinical use of disulfiram mimics the effects seen in individuals with ALDH2 deficiency. A common variation that causes deficiency is the ALDH2*2 allele, which affects an estimated 540 million people of East Asian ancestry. ALDH2 variants can be found in other ethnic groups, but they are less common. It is estimated that 120 million people of non-East Asian genetic ancestry have reduced ALDH2 enzymatic activity.