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Disulfiram has been widely used as an adjunct in the treatment of alcoholism and has relatively few side effects. An alcoholic patient who developed hepatotoxic reaction while on disulfiram therapy is described. Although such reactions may occur, the dangers of continued drinking outweigh the dangers of taking disulfiram for the alcoholic.
A case of an adult with disulfiram-induced hepatitis is presented. An etiological role for the drug was proved when the patient underwent a provocative challenge and developed evidence of hepatocellular damage, reversible on withdrawal of the drug. Disulfiram-induced liver injury is difficult to detect in a population with a high incidence of alcohol-related hepatic disease. Liver chemistries should be screened before beginning disulfiram therapy and periodically during treatment.
Effects of barbital and disulfiram on the metabolism of serotonin (5-HT) in vivo were studied. One hr after intracerebroventricular injection of [14C]-5-HT (3 nmoles, 0.5 muCi), the levels of the total and deaminated radioactive materials were increased in rats receiving either barbital or disulfiram, as compared to those of control rats. In addition, an additive effect was observed by a combined administration of these two drugs. The results in this paper strongly suggest that barbital and disulfiram inhibit the metabolism of 5-hydroxyindoleacetaldehyde (5-HIAAld), a first deaminated metabolite in 5-HT metabolism.
A 28-year-old woman experienced a confusional attack with hallucinations associated with moderate motor deficiency of the lower limbs during treatment with disulfiram 1 g/day. Later on, a temporary increase in disulfiram dosage to 1.75 g/day was followed by quadriplegia and paralysis of the facial and glosso-pharyngeal nerves. Paralysis regressed rapidly in the cranial and upper limb areas, but very slowly in the lower limbs. Disulfiram-induced peripheral neuropathies are not uncommon. They may take various forms, such as optic neuritis, polyneuritis of the limbs and, exceptionally, severe multiple paralysis with psychic disorders, as in the case reported here.
In cirrhotic, steatosic and healthy subjects, the authors studied the metabolism of disulfiram (TETD) administrated orally (500 mg) 3 consecutive days. Carbon disulfide (CS2) and the whole TETD, diethyl dithiocarbamate (DDC) disulfides, were determined by a gas chromatographic method. The evolution of metabolites is similar in steatosic and healthy subjects. In cirrhotics the CS2, DDC and disulfides level increase within the 3 days. This phenomenon may be related with hepatic toxicity of TETD and with the persistence of disulfiram-alcohol reaction. The authors suggest to use low doses of disulfiram in cirrhotic.
Thirty male alcoholic inpatients received in a random double-blind design placebo (P) or disulfiram 250 mg. (D) at bedtime in order to evaluate the effects of the latter on EEG-EOG sleep patterns. Subjects (S's) had no major medical illness and required no medication for 3 weeks prior to the study. There were 13 disulfiram S's and 17 placebo S's. The total REM time decreased significantly (p less than 0.05) in the D group. Total number of REM episodes decreased and latency to stage 1 REM increased in the disulfiram group. These results are characteristic of sleep patterns induced by the administration of catecholaminergics and opposite to those induced by catecholamine inhibiting agents.
An alcoholic patient had a gradual increase of BP while he was treated with disulfiram. The BP returned to normal after the disulfiram was withdrawn. Increased BP should be considered a possible side effect of long-term disulfiram therapy, especially in the presence of alcohol-induced liver damage.
The urinary excretion of vanillylmandelic acid (VMA), homovanillic acid (HVA) and total metanephrines (TMNs) was studied in a group of White male alcoholic patients under three experimental conditions--on admission and prior to treatment, after 7 days of administration of a placebo, and after 9 days of administration of disulfiram 400 mg/d Disulfiram caused a significant decrease in VMA levels compared with the pretreatment (P less than 0,01) and placebo (P less than 0,05) levels. The output of HVA and TMNs was unchanged. It is suggested that disulfiram may produce false-negative results in cases of suspected phaeochromocytoma if VMA levels only are assayed. TMNs would appear to be the measurement of choice in such a situation.
Thirty male sober alcoholic inpatients received placebo or disulfiram in a random double-blind design in order to evaluate the effects of disulfiram on nocturnal penile tumescence. The amount and frequency of full erections were decreased in the cohort receiving disulfiram. Implications of these results for the role of norepinephrine in penile tumescence are discussed.
The colorimetric reaction of cuprous iodide and disulfiram has been collaboratively studied in 8 laboratories to determine the drug in tablet form at 2 dosage levels. The disulfiram was extracted from the tablet matrix with methylene chloride. After a basic wash with 1 M NaOH, an aliquot of the methylene chloride solution was reacted with solid cuprous iodide, and the absorbance of the resulting color was measured. Single assays on 2 synthetic preparations of known disulfiram content were performed with average recoveries of 98.4 and 99.2% for 93.3 and 105.3 mg, respectively. Duplicate determinations on 2 commercial tablet preparations declared at 250 and 500 mg gave mean and standard deviation values of 246.6 +/- 6.40 and 493.6 +/- 12.0 mg, respectively. The results agreed closely with those obtained by the author using the NF iodometric titration procedure. The method has been adopted official first action.
Disulfiram (Antabuse) is used extensively in the management of alcoholism and, although mild psychiatric symptoms are quite common side-effects of treatment with this drug, psychotic reactions rarely occur. With the high doses of disulfiram used in earlier days, the incidence of 'psychosis' was estimated at 2 - 20%. A more recent review suggests that the incidence is far lower and that the 'psychosis' described in many cases consisted of mild psychiatric disturbances, such as anxiety and sedation, as well as a more florid psychosis or an organic brain syndrome. Of the 52 cases reported in the English-language literature, only 9 reflect psychotic reactions to disulfiram, the remainder being schizophrenic or developing a picture of organic brain syndrome. We report a case because of its implications.
In a retrospective investigation we report our experience with alcohol-dependent patients who were hospitalized between 1987 and 1990. There were 58 patients, 29% of them were hospitalized several times. In the middle of 1991 and 1992 we interviewed the family doctors and the social workers who cared for the patients. In 48% of the patients there was improvement, in 24% there was a stabilization, and in 28% we noted a deterioration. There was no difference in patients treated by the family doctor alone or in patients treated by the social workers. Comparing patients taking Disulfiram with patients taking no drug, there was no difference in improvement (48% versus 50%). But the good results in patients not taking disulfiram were nearly exclusively noted for those who had been hospitalized in a special clinic for alcohol-dependent persons. Patients who were hospitalized several times for alcohol withdrawal had a worse chance to improve their situation (-20%). The therapy with disulfiram in alcohol-dependent patients is helpful to cure chronic alcoholics. Programs in a specialized clinic improve also the chance to be cured of the addiction.
Blood variations of bradykininogen and bradykinin have been measured in the Dog after single or combined treatments with ethanol and disulfiram. Ethanol only induces hyperbradykinnemia and chronic disulfiram decreases plasmatic level of bradykinnogen without modifying bradykinn. During associated treatment disulfiram-ethanol, physiological disturbances are observed in bradykinin formation; these disturbances can explain partly vasomotor reaction following treatments.
This paper reviews the controlled studies which have led to the increasing recognition that supervised disulfiram is one of the few demonstrably effective interventions in alcoholism, both alone and as an adjunct to psychosocial methods. The specifically behavioural implications of disulfiram treatment are also noted. It examines techniques for maximising disulfiram's therapeutic effectiveness and reviews recent research into its pharmacokinetics, mode of action, toxicology and bioavailability. Finally, the prospects for an effective depot preparation are discussed.
The effect of disulfiram (teturam, antabus) (200 mg/kg, intragastrically) on the rat brain glycolipid structure was studied. It was found that disulfiram increased the contents of cerebrosides I and III in nervous tissue. The administration of alcohol (1 g/kg, 20% solution, intraperitoneally), with disulfiram being simultaneously administered, was accompanied by increased levels of brain cerebrosides I and II.
In our study we have tried to compare the prophylactic effects of superoxide dismutase (SOD), SOD+catalase (CAT), desferrioxamine, verapamil and disulfiram, which are all free oxygen radical (FOR) scavengers, in an animal model of experimental acetic acid colitis. The control group had 58.3% colonic ulcers. The SOD group (48.6% ulcerated area) and the SOD+CAT group (47.2% ulcerated area) did not show a significant difference when compared with the control group. The values were significantly different in all other groups when compared with the control group (desferrioxamine (29.2% ulcerated area): P < 0.01; verapamil (10.4% ulcerated area) and disulfiram (7.6% ulcerated area): P < 0.001. In conclusion, desferrioxamine, verapamil and disulfiram have been found to be effective as prophylactics in experimental acetic acid colitis.
Disulfiram treatment caused marked elevations of circulating blood acetone levels in rat and man. In the rat, disulfiram (0.59 g/kg, p.o.) given singly or for three consecutive days increased the fasting blood acetone levels 5- and 25-fold, fespectively. Circulating acetone levels were also estimated noninvasively in man by measuring acetone in the expired air. A 15-fold increase in the expired air acetone levels was observed in a group of five male non-fasting subjects taking disulfiram (250 mg daily) for a minimum of one month, when compared to control subjects.
The disulfiram-ethanol reaction is a well-known clinical phenomenon occurring as a result of acetaldehyde accumulation in the blood. Symptoms usually begin within 5-15 minutes after ingestion of ethanol in patients who have taken disulfiram 3-123 hours earlier, and generally occur in the following order: flushing, sweating, palpitations, dyspnea, hyperventilation, increased pulse rate, fall in blood pressure, nausea, vomiting, and drowsiness. Patients need not experience all these symptoms, and recovery is generally complete. Trimethoprim-sulfamethoxazole (cotrimoxazole) is a commonly prescribed antimicrobial agent that may produce a reaction similar to that of disulfiram when taken by patients who drink ethanol. This drug-chemical interaction may result in accumulation of acetaldehyde in the blood.