Use Of Disulfiram Research Articles

Use of disulfiram in psychological treatment of multiply hospitalized alcoholics.

Use of disulfiram in psychological treatment of multiply hospitalized alcoholics.

Use of disulfiram in psychological treatment of multiply hospitalized alcoholics.

Use of disulfiram in psychological treatment of multiply hospitalized alcoholics.

Disulfiram intoxication in a child

DISULFIRAM INHIBITS acetaldehyde dehydrogenase, which catalyzes the oxidation of acetaldehyde, the init ial product of e thanol metabolism. Ingest ion of e thanol while this enzyme is inhibi ted results in accumula t ion of acetaldehyde, causing flushing, diaphoresis, vomiting, tachycardia, headache, chest pain, dyspnea, and anxiety, which persist for hours. These unpleasant symptoms are the basis for use of disulfiram in alcohol rehabi l i ta t ion programs, reinforcing motivat ion to avoid ethanol use. Disulf i ram is relatively nontoxic, but untoward effects have been observed af ter large doses or extended periods of t reatment . The widespread use of disulfiram (200,000 pat ients in the Uni ted Sta tes at any given time; Ayerst Laborator ies , te lephone communica t ion , 1983) in sett ings associated with accidental poisoning in children (unemployment , mar i ta l discord and instability, and alcoholic family members) leads us to suspect tha t this intoxicat ion may be underdiagnosed in this country. We found only six reports of chi ldhood intoxicat ion? -7 We report an addi t ional case of disulfiram intoxicat ion in a child, and discuss the distinctive features of this syndrome in children.

Alcoholism. Images, impairments, interventions.

Diagnosis of alcoholism requires a vigilant attitude and aggressive pursuit of supporting evidence by the primary care physician. Because the alcoholic is characteristically defensive and commonly denies the diagnosis, the physician must be persistent and honest when confronting the patient. Effective treatment is available through programs comprising patient and family education, psychotherapy, medical supervision, involvement in Alcoholics Anonymous, use of disulfiram (Antabuse), and follow-up care. Since the recovering alcoholic is vulnerable to relapse, long-term maintenance of sobriety requires not only abstinence from alcohol but also avoidance of psychoactive and narcotic drugs.

Fulminant Hepatitis Associated With Disulfiram

Disulfiram is used commonly as reinforcement in the treatment of chronic alcoholism. Although the drug is generally considered safe, there are reports of side effects including psychosis and hepatitis. We report a case of fatal fulminant hepatitis caused by the use of disulfiram in a man with previously normal hepatocellular function.

Principles of disulfiram use

Considerable experience has accumulated in the years since disulfiram was introduced as an aid to recovery from alcoholism. It is now clear that successful use requires that the drug be part of an overall treatment program and that the patients selected voluntarily and willingly participate in this program. Compliance and the desire for long-term change are the key. The author presents a 12-step pretreatment approach, with which the prescribing physician can ensure that the drug is being appropriately integrated into the overall program and is being used in suitably motivated patients.

Can disulfiram use precipitate urges to drink alcohol?

Although pharmacological data suggest that patients taking disulfiram should have a reduced desire to drink alcohol, voluntary compliance with disulfiram treatment is quite poor. As a possible explanation for why so many patients discontinue taking disulfiram and return to excessive drinking, it was hypothesized that daily disulfiram administration might serve as a cognitive stimulus precipitating urges to drink alcohol and/or inadvertently exposing patients to additional drinking-related cues. If this is the case, then patients taking disulfiram should report more thoughts about or urges to drink alcohol. In an explanatory, uncontrolled clinical study, alcohol abusers who were taking disulfiram tended to self-record more cravings for alcohol over a two week period than did abstinent patients who were not taking disulfiram. Controlled research is needed to investigate whether disulfiram use may serve as a cue antecedent to relapse to drinking.

Regulation of polypeptide synthesis in endothelial cells and hybridoma cells by the copper ionophore disulfiram

Treatment of two clonal lines of vascular endothelial cells, two lines of antibody producing hybridoma cells and their parental line of myeloma cells with the anti-alcoholism copper lonophore, disulfiram, leads to rapid and irreversible depression of protein synthesis. In particular, synthesis of the biologically active molecules fibronectin, collagen and immunoglobulins was depressed. In contrast, disulfiram induced several novel ‘stress’ proteins in endothelial cells. These results suggest that clinical use of disulfiram may cause profound biochemical imbalance in tissues of the vasculature and of the immune system.

A review of the clinical use of disulfiram and calcium carbimide in alcoholism treatment.

The role of disulfiram and calcium carbimide in alcoholism treatment is currently under critical review. Evidence supporting the efficacy of these drugs is unclear: although many alcoholism therapists are of the opinion that the alcohol deterrents are useful in the treatment of the chronic alcoholic, clinical studies with disulfiram that use proper evaluation methodologies report no or only low improvement rates, and there have been no controlled studies with calcium carbimide. Although disulfiram is thought to be safe when administered in therapeutic dosages, toxicity can occur in alcoholics treated with this drug. Information concerning the toxicity of calcium carbimide in alcoholics is incomplete. In this article, the efficacy and toxicity of disulfiram and calcium carbimide are reviewed, and guidelines for their safe and effective use in alcoholism treatment are presented.

Effect of disulfiram on adrenergic function

Disulfiram inhibits dopamine β‐hydroxylase activity, and in animals dopamine (3‐hydroxylase activity becomes rate‐limiting in norepinephrine synthesis. It has been suggested that altered synthesis disturbs adrenergic function and plays a role in the hypotensive aspect of the ethanol‐disulfiram reaction in man. We evaluated adrenergic function in 7 normal subjects before and during disulfiram administration, 500 mg/day orally, for 2 wk. Urinary excretion of vanilmandelic acid (VMA) (5.8 ± 0.45 to 2.8 ± 0.31 mgl24 hr, p < 0.01) and norepinephrine (37.8 ± 6.5 to 16.3 ± 2.9 µg/24 hr, p < 0.02) decreased, whereas homovanillic acid (HVA) (4.0 ± 0.4 to 13.9 ± 3.2 mg/24 hr, p < 0.05) increased during disulfiram. During disulfiram use, blood pressure rose in the supine position (from 125/71 to 136/83 mm Hg, p < 0.01) and after 2 min of standing (from 120/87 to 138/97, p < 0.01) in all subjects. In response to nitroglycerin and upright posture, systolic hypotension was greater during disulfiram use (19.1 ± 2.2 vs 29.3 ± 1.8 mm Hg, p < 0.01); hypotension‐associated heart rate responses (change in heart rate/change in systolic blood pressure) were diminished (from 2.8 ± 0.5 to 1.9 ± 0.2 beats/min/mm Hg, p < 0.02). Disulfiram had no effect on pressor responses to tryamine and norepinephrine. Urinary excretion data were consistent with reduced norepinephrine synthesis during disulfiram administration. The cardiovascular responses to usual activities were unchanged by disulfiram, although with extreme hypotensive stress there was evidence of impaired response.

Use of disulfiram in histochemical study of effect of different stimuli on content of noradrenaline in brain structures.

1. In the absence of preliminary inhibition of synthesis weak stimuli do not cause changes in the level of fluorescence of noradrenaline in the structures investigated. 2. A decrease in the level of fluorescence of noradrenaline in brain structures, a decrease in the components of “open field” behavior, and deterioration of the reproduction of a conditioned response of passive avoidance were found 12 h after administration of 200 mg/kg disulfiram. 3. Preliminary inhibition of noradrenaline synthesis by disulfiram makes it possible to detect a decrease in the level of noradrenaline fluorescence in brain structures both upon electrical stimulation of the stimuli and in testing the rats in an “open field” and upon the reproduction of a conditioned response of passive avoidance.

Methodological problems in the search for antialcoholic remedies (literature review)

Methods used currently in the treatment of alcoholism, such as conditioned reflex therapy, the creation of intolerance, sensitization to alcohol by the use of disulfiram, etc., are unsatisfactory to clinicians because they are not sufficiently effective, and also because of serious side effects and complications which accompany treatment with drugs like disulfiram. Medicines are needed which are more effective and have a wider range of therapeutic activity. The massive search for new antialcoholic substances is quite possible under conditions of well-designed animal experiments. Nevertheless, the experimental methods for searching for such substances are virtually undeveloped. Models of chronic alcoholism in animals, used advantageously in the study of the pathogenesis of this illness, are not always satisfactory for screening antialcoholic drugs. It is therefore appropriate to consider the basic studies of this subject in developing the most efficient directions for experimental selection of new antialcoholic drugs. In screening studies, one must attempt to satisfy the following requirements: 1) models of chronic alcoholism should develop the disorder in a comparatively short time; 2) the experiments should be easily and precisely reproducible and should have clearly quantitative characteristics permitting comparison in the presence of several variables, of which the medication is one. Analysis of the experimental data of different investigators illustrates the necessity of meeting certain conditions in establishing models of chronic alcoholism. One of the most important conditions is the correct choice of experimental animals. Different animal species are not equally easily induced to develop alcohol addiction. The Finnish investigators, Arvola and Forsander [1, 2] compared the ability to develop alcohol addiction in six animal species: hedgehog, golden hamster, guinea pig, rabbit, white rat, and mouse. The consumption of a 10% solution of ethanol was studied under conditions of free choice. The golden hamster consumed the largest quantity of alcohol, the guinea pig the least. The hamster also most sharply distinguished solutions with lower alcohol concentrations, and also freely consumed alcohol solutions of a wide range of concentrattens. Komura et al. [3], came to analogous conclusions and, furthermore, established a correlation between alcoholic consumption by animals and the activity level of alcohol dehydrogenase in the liver. In their experiments additional alcohol consumption was easily developed in golden hamsters and some strains of mice. These animals had the highest levels of alcohol dehydrogenase activity, while guinea pigs had a low level of alcohol consumption and of enzyme activity. The authors suggest the use of these criteria in the selection of animals as experimental models for chronic alcoholism. Although experiments have been conducted successfully on various animals and birds, including monkeys, dogs, miniature pigs, pigeons, etc., most studies show a preference for working with traditional laboratory animals, rats and mice. For these it is necessary to specify the strain, the sex, and the age of the animals, the conditions under which they are maintained, and their diet. Numerous studies have shown that addiction is most easily developed in mice of the C57B1 strain and its hybrids. Mice of the KR and DBA strains avoid Consuming alcohol. Such a relationship to alcohol can de

Disulfiram Therapy in Alcoholism: Patient Compliance Studied with a Urine‐Detection Procedure

SUMMARYA simple urine test to verify disulfiram (Antabuse®) use has been developed. Compliance with disulfiram therapy was determined in 95 consecutive abstinent alcoholic patients in an outpatient clinic. All patients were allegedly taking disulfiram. Twenty percent of them were found not to be using the drug, even though they said they were. Disulfiram is unusual because it is probably the patient's belief that he is taking it that is therapeutic, not the action of the drug. Because of this, it is difficult to incorporate placebo controls and double‐blind procedures into studies of disulfiram efficacy. However, with any research design, no conclusions will be valid if based solely on patients' reports of use.

Alcoholism Treatment in Private Psychiatric Hospitals; a National Survey

Responses from 71 of 128 private psychiatric hospitals indicated that 91% treated alcoholics chiefly by psychotherapeutic means, with considerable use of Alcoholics Anonymous and disulfiram.

Combined Use of Lithium and Disulfiram

Combined Use of Lithium and Disulfiram

Alcohol in cough medicines hazard to disulfiram user.

To the Editor.— The use of disulfiram (Antabuse) as an adjunct to alcoholism treatment programs is well known in this country, and may be increasing. 1 The minimal dose of alcohol necessary to evoke a reaction in the disulfiram treated patient is somewhat controversial, 2 although it has been suggested that as little as 7 ml of alcohol may cause typical reactions. 3 Thus, in disguised forms, alcohol could represent a serious hazard for patients receiving disulfiram. Our experience with a patient who had a disulfiram-alcohol reaction following the ingestion of a single dose of an over-the-counter, widely advertised cough medication, containing 25% alcohol, serves to emphasize the dangers of alcohol-containing preparations in these unique patients. Report of a Case.— The patient, a 46-year-old white man, was admitted to the hospital because of the abrupt onset of nausea, vomiting, and flushing of several hours' duration. He had been a heavy

Use of Disulfiram (Antabuse) in Alcoholism

Use of Disulfiram (Antabuse) in Alcoholism

Combined Use of Disulfiram and Metronidazole in Treatment of Alcoholism

Combined Use of Disulfiram and Metronidazole in Treatment of Alcoholism

Disulfiram—Alcohol Side Effects

To the Editor:— I certainly do agree with the tenor of what Dr. Fox says regarding the use of disulfiram and would like to state very clearly that I continue to use it and strongly believe in it as an adjunct in the treatment of alcoholism. I reported the reaction since I felt that it was quite a striking one and because the reaction occurred in an individual who was not by any means otherwise psychotic. The individual on which I reported had functioned well in the community prior to that episode, which was the first and only one of its kind for him. There have been none since. As a matter of fact, I am not sure that he could have been classified as an alcoholic in the usual sense, but instead as a heavy drinker. More recently, I have been using disulfiram with people who are not alcoholics,

Lymphocytopenia induced in a strain of laboratory mice by agents commonly used in treatment of ectoparasites.

SummaryThe normal leucocyte picture of heart blood of the Prince Henry strain of mice is presented. Tetmosol and Lanokil have been shown capable of producing gross modification to this picture by inducing an acute lymphocytopenia. The results are discussed with respect to immunological aberrations‐which might follow the use of disulfiram for the treatment of chronic alcoholism.