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Disulfiram implants in the treatment of alcoholism some mechanisms of action.

For nearly 20 years, disulfiram implanted subcutaneously, has been used in alcoholics who have failed to respond to other treatment. Significantly positive results have been reported in a large number of cases. Despite this extensive use, many questions remain as to how these effects are exerted. As the reaction to alcohol following disulfiram implantation occurs less frequently and in lower intensity than following oral ingestion, psychological mechanisms probably play a vital role. Based in part on out own recent series of cases, the following explanations are offered regarding the possible mechanisms of action: (1) high motivation to stop drinking is manifested by agreeing to the precedure and reinforced by the procedure; (2) palpable presence of hte drug in the site of implantation; (3) generally sufficient reactivity of the agent to indicate activity to the patient;(4) in obsessional patients there is a removal of the fear of resumption of drinking for an extended period of time. For the more sociopathic patients the implant appears to provide a more structured ego boundary to allow the patient to change.

Adult↗

Increased sympathetic nervous system activity in alcoholic patients treated with disulfiram.

The authors measured plasma levels of norepinephrine (NE) and dopamine beta-hydroxylase (DBH), pulse rates, and blood pressures of 81 hospitalized alcoholic patients. Treatment with 500 mg/day of disulfiram (but not 250 mg/day or placebo) resulted in small but significant increases in plasma NE and in blood pressure. The 500-mg dose did not appreciably inhibit DBH. Patients receiving high doses of disulfiram should have their blood pressure monitored and their dose decreased to 250 mg/day when possible.

Adult↗

Disulfiram encephalopathy as a cause of the catatonia syndrome.

The authors describe a case of the catatonia syndrome associated with disulfiram therapy. Although useful in the management of chronic alcoholism, disulfiram is being increasingly associated with a wide spectrum of side effects and untoward medical sequelae, which now include catatonia. The authors note that catatonia is a clinical syndrome associated with multiple medical conditions as well as psychiatric disorders.

Adult↗

Case report of acute disulfiram overdose.

The authors describe the clinical symptoms of a disulfiram overdose in a male patient and present the plasma concentrations of disulfiram and its metabolites 4 and 7 days after the overdose.

Acute Disease↗

Pharmacokinetic interaction of disulfiram and antidepressants.

Intravenous imipramine and desipramine were administered to two detoxified alcoholics before and during disulfiram treatment. Tricyclic pharmacokinetic parameters, determined from plasma samples over 48 hours, indicated decreased total body clearance, increased elimination half-life, and higher peak plasma levels during disulfiram treatment.

Adult↗

Do ethanol and metronidazole interact to produce a disulfiram-like reaction?

OBJECTIVE: To obtain and evaluate evidence about the supposed disulfiram-like interaction between metronidazole and ethanol. DATA SOURCES: MEDLINE search from January 1964 to June 1999, using the terms metronidazole, ethanol, and drug reaction. DATA SYNTHESIS: The manufacturer's warnings include a disulfiram-like reaction between metronidazole and ethanol. However, review of reports published between 1969 and 1982 produced no convincing evidence that this reaction exists. Six case reports involving eight patients were evaluated. CONCLUSIONS: Four of the eight cases were serious, including one death, but the authors of all the reports presumed the metronidazole-ethanol reaction to be an established pharmacologic fact. None provided evidence that could justify their conclusions.

Alcohol Deterrents↗

Reevaluation of the disulfiram-alcohol reaction in man.

The intensity of the disulfiram-alcohol reaction is found to depend on the blood acetaldehyde level, a disulfiram-induced predisposition reflected by alkalosis, and an individual predisposition reflected by dopamine-beta-hydroxylase activity.

Alcoholism↗

Control orientation and disulfiram.

Alcoholics electing to take disulfiram were significantly more externally oriented, as measured by Rotter's Internal-External Locus of Control Scale, than were alcoholics not electing to take disulfiram.

Adult↗

Behavioral use of disulfiram in the treatment of problem drinking.

As part of an outpatient treatment research project alternative ways of using Antabuse (disulfiram) in the treatment of problem drinkers are developed. Instead of forced regular use, Antabuse was administered as a voluntary situational therapeutic tool. Subjects were 84 men and 51 women. Thirty percent of both men and women decided to use Antabuse. Men most often used disulfiram continuously for a longer period or to stop an ongoing drinking period. The women used Antabuse to secure shorter periods of abstinence as part of their drinking schedules and to prevent drinking in specific high-risk situations. The subjects using Antabuse reduced their ethanol consumption significantly (p less than .05) at the end of the follow-up period, compared to the nonusers.

Adult↗

Inhibitory effect of ethanol administration on beta-alanine-2-oxoglutarate aminotransferase (GABA aminotransferase) in disulfiram-pretreated rats.

Ethanol in the presence of disulfiram (N,N,N',N'-tetraethylthiuram disulfide, an inhibitor of aldehyde dehydrogenase) inhibited liver beta-alanine-oxoglutarate aminotransferase (beta-AlaAT I) activity yet activated tyrosine aminotransferase (TAT) in weanling rats in vivo. The effect on beta-AlaAT I was followed by the inhibitory expression of beta-AlaAT I mRNA. The beta-AlaAT I activity was reduced with a pseudo-first-order profile with time, and the half-life was calculated to be 12.3 +/- 0.83 h with the rate constant (Kd) of 0.056 +/- 0.004 h-1. The synthesis of beta-AlaAT I in rat liver was estimated to be 1.56 x 10(-10) mol/g of wet tissue per hour at a steady state. A combination of ethanol and disulfiram also reduced beta-alanine-pyruvate aminotransferase (beta-AlaAT II) activity to 60% of the control after 24 h.

4-Aminobutyrate Transaminase↗

Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: is there still a role for these drugs?

Disulfiram and calcium carbimide are two alcohol deterrants widely used in alcoholism treatment, however, there exist great concerns over their safety. Reports on hepatotoxicity, mainly related to disulfiram therapy, have been published. The hepatotoxic potential of calcium carbimide is less well characterized. Here, we describe four cases of liver damage related to this therapeutic group that were submitted to a Registry of hepatotoxicity and point out the limitations that we face when prescribing these compounds. A reassessment of the role of these compounds in the management of alcohol dependence is clearly needed.

Adult↗

Disulfiram-induced fulminant hepatic failure in an active duty soldier.

Fulminant hepatic failure is a rare complication of disulfiram treatment for alcoholism. In the instances that it does occur, previous liver disease or failure to be abstinent from alcohol are thought to be causative. This case describes fulminant hepatic failure in a patient taking disulfiram with no previous liver disease and report of being compliant with alcohol abstinence. Careful pretreatment screening and rigorous monitoring patients are recommended to help prevent this life-threatening event.

Adult↗

[Acute disulfiram intoxication with severe neurological sequaelae and presenting misleading psychiatric deficiency].

Disulfiram self poisoning is exceptional. The authors report on the case of such an intoxication related to the ingestion of a potentially lethal dose of this drug (30 g) and draw the attention on the following points: 1) The initial signs may be misleading because they include both psychiatrics and neurological signs such as phonation abnormalities, myoclonias and tetraparesia. 2) The evolution is unforseeable with the possible occurrence of severe psychological and motricity sequaelae, associated with bilateral and symetric injuries of the putamen, the palladium and the basal nuclei on CT-scan (or MRI). The pathophysiologic al mechanisms of theses signs are discussed, and the need for disulfiram in the care of alcoholic patients seeking for withdrawal as well.

Adult↗

[Evaluation of disulfiram treatment in chronic alcoholism].

Disulfiram is an effective therapeutic agent in the treatment of chronic alcoholism as long as certain conditions are maintained; the patient realises that he is ill, the patient is motivated to be treated and that alcohol withdrawal be maintained chiefly during the first year where there is periodic uneasiness. Disulfiram therapy must only be prescribed in the phase where the chronic alcoholic accepts the treatment and not in the phase where he negates it.

Alcoholism↗