Disulfiram

Facial dushing after ingestion of alcohol occurs in up to one-third of patients taking chlorpropamide. The mechanism, like that of the disulfiram reaction, probably involves inhibition of the oxidation of acetaldehyde, a metaboUte of ethanol. The plasma concentration of chlorpropamide may be correlated with chlorpropamide—alcohol dushing. 

DISTEARYL PEROXYDI-CARBONATE DISUCCINIC ACID PEROXIDE, 72X In water DISUCCINIC ACID PEROXIDE, technical pure DISULFIRAM... 

Disulfiram may be made by the reaction of diethyl amine with carbon disulfide in the presence of sodium hydroxide. The (CjHjljNCSSNa intermediate is oxidatively coupled using hydrogen peroxide to give disulfiram. 

Diethylacetylamino malonate Hydroxytryptophan Diet hy lal ly I-(1 -met hylbutyl) malonate Thiamylal Diethylamine Amodiaquin Benzquinamide Bialamicol Diethylpropion HCI Disulfiram Ethamivan... 

Ethanol is almost entirely metabolized in the liver. The first step, oxidation by alcohol dehydrogenase, yields acetaldehyde, a reactive and toxic compound. Essentially all of the acetaldehyde is converted to acetate by the liver enzyme aldehyde dehydrogenase. Aldehyde dehydrogenase is inhibited by the drag disulfiram. Given alone, disulfiram is a nontoxic substance. However, ethanol consumption in the presence of... 

Procarbazine causes myelosuppression, hypnotic and other effects on the central nervous system, e.g., vivid nightmares. Also, procarbazine causes a disulfiram like syndrome on ingestion of ethanol. 

The effects of warfarin may increase when administered with acetaminophen, NSAIDs, beta blockers, disulfiram, isoniazid, chloral hydrate, loop diuretics, aminoglycosides, cimetidine, tetracyclines, and cephalosporins. Oral contraceptives, ascorbic acid, barbiturates, diuretics, and vitamin K decrease the effects of warfarin. Because die effects of warfarin are influenced by many drugp, die patient must notify die nurse or die primary healdi care provider when taking a new drug or discontinuing... 

Ethanol is oxidized by alcohol dehydrogenase (in the presence of nicotinamide adenine dinucleotide [NAD]) or the microsomal ethanol oxidizing system (MEOS) (in the presence of reduced nicotinamide adenine dinucleotide phosphate [NADPH]). Acetaldehyde, the first product in ethanol oxidation, is metabolized to acetic acid by aldehyde dehydrogenase in the presence of NAD. Acetic acid is broken down through the citric acid cycle to carbon dioxide (CO2) and water (H2O). Impairment of the metabolism of acetaldehyde to acetic acid is the major mechanism of action of disulfiram for the treatment of alcoholism. 

One fascinating aspect of the effect of the genetic polymorphisms described earlier is that acculturation can partially overcome the protective factor, and Asian groups born in North America may have only partial protection (Goldman 1993 Tu and Israel 1995). In individuals who consume small amounts of alcohol over time, the aversive effects diminish, an effect similar to that described in clinical reports of patients who developed a resistance to the effects of disulfiram. 

Pharmacology. Disulfiram is almost completely absorbed after oral administration. Because it binds irreversibly to ALDH, renewed enzyme activity requires the synthesis of new enzyme. This feature creates the potential for the occurrence of a DER for at least 2 weeks after the last ingestion of disulfiram. Consequently, alcohol should be avoided during this period. 

Disulfiram produces a variety of adverse effects, which commonly include drowsiness, lethargy, and fatigue (Chick 1999). Other more serious adverse effects, such as optic neuritis, peripheral neuropathy, and hepatotoxicity, are rare. Psychiatric effects of disulfiram are also uncommon. They probably occur only at higher dosages of the drug and may result from the inhibition by disulfiram of a variety of enzymes in addition to ALDH. Included among the enzymes inhibited by disulfiram is dopamine P-hydroxylase, inhibition of which increases dopamine levels, which in turn can exacerbate psychotic symptoms in patients with schizophrenia and occasionally may result in psychotic or depressive symptoms in patients without schizophrenia. 

Disulfiram is usually given orally. Because there is an increased risk of side effects and toxic hazards as the dosage is increased, the daily dosage prescribed in the United States has been limited to 250—500 mg/day. However, efforts to titrate the dosage of disulfiram in relation to a challenge dose of ethanol indicated that some patients require in excess of 1 g/day of disulfiram to reach blood levels sufficient to produce a DER (Brewer 1984). 

In deciding whether disulfiram should be used in alcoholism rehabilitation, patients should be made aware of the hazards of the medication, including the need to avoid over-the-counter preparations that include alcohol, the need to avoid drugs that can interact with disulfiram, and the potential for a DER to be precipitated by alcohol used in food preparation. The administration of disulfiram to anyone who does not agree to use it, who does not seek to be abstinent from alcohol, or who has any psychological or medical contraindications is not recommended. 

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