Disulfiram acts by inhibiting aldehyde dehydrogenase. Alcohol is metabolized as usual, but acetaldehyde accumulates. Thus, disulfiram causes extreme discomfort in patients who drink alcoholic beverages. Disulfiram alone has little effect; however, flushing, throbbing headache, nausea, vomiting, sweating, hypotension, and confusion occur within a few minutes after an individual taking disulfiram drinks alcohol. The effects may last 30 minutes in mild cases or several hours in severe ones. Because adherence to disulfiram therapy is low and because evidence from clinical trials for its effectiveness is weak, disulfiram is no longer commonly used.
Disulfiram is rapidly and completely absorbed from the gastrointestinal tract; however, a period of 12 hours is required for its full action. Its elimination is slow, and its action may persist for several days after the last dose. The drug inhibits the metabolism of many other therapeutic agents, including phenytoin, oral anticoagulants, and isoniazid. It should not be administered with medications that contain alcohol, including nonprescription medications such as those listed in Table 63–3. Disulfiram can cause small increases in hepatic transaminases. Its safety in pregnancy has not been demonstrated.
Several other drugs have shown efficacy in maintaining abstinence and reducing craving in chronic alcoholism, although none has FDA approval yet for this use. Such drugs include antiseizure agents (topiramate, gabapentin, and valproate, see Chapter 24); and baclofen, a GABA receptor antagonist used as a spasmolytic (see Chapter 27). Studies of varenicline (see Chapter 7) indicate that this nicotinic agonist drug can reduce binge drinking in mice. Clinical trials of selective serotonin reuptake inhibitors (SSRIs, see Chapter 30) and ondansetron, a 5-HT3 antagonist (see Chapter 62) yielded negative results overall, but suggested that these agents may have benefits in certain subgroups of patients. Based on evidence from model systems, efforts are under way to explore agents that modulate cannabinoid CB1 receptors, corticotropin-releasing factor receptors, and GABA receptor systems, as well as several other possible targets. Rimonabant, a CB1 receptor antagonist, has been shown to suppress alcohol-related behaviors in animal models and is being tested in clinical trials of alcoholism.
Other alcohols related to ethanol have wide applications as industrial solvents and occasionally cause severe poisoning. Of these, methanol and ethylene glycol are two of the most common causes of intoxication. Isopropyl alcohol (isopropanol, rubbing alcohol) is another alcohol that is sometimes ingested when ethanol is not available. It produces coma and gastrointestinal irritation, nausea, and vomiting, but is not usually associated with retinal or renal injury.
Methanol (methyl alcohol, wood alcohol) is widely used in the industrial production of synthetic organic compounds and as a constituent of many commercial solvents. In the home, methanol is most frequently found in the form of “canned heat” or in windshield-washing products. Poisonings occur from accidental ingestion of methanol-containing products or when it is misguidedly ingested as an ethanol substitute.
Methanol can be absorbed through the skin or from the respiratory or gastrointestinal tract and is then distributed in body water. The primary mechanism of elimination of methanol in humans is by oxidation to formaldehyde, formic acid, and CO2 (Figure 23–3).