Pharmacoprophylaxis of alcohol dependence: Review and update Part I: Pharmacology

Abstract

Alcohol dependence is a major problem in India. The pharmacological armamentarium for relapse prevention of alcohol has widened with the addition of new drugs. In this article, we review the pharmacology and efficacy of the four most important such drugs: disulfiram, naltrexone, acamprosate and topiramate. The first part of this two-part review series concerns the comparative pharmacology and the second part concerns the efficacy studies. Overall, all four of these drugs have modest but clinically significant usefulness as pharmacoprophylactic agents for relapse prevention or minimization of alcohol dependence. Combinations might be helpful, especially for naltrexone and acamprosate. The issue of supervision and compliance remains important, especially for such drugs as disulfiram and naltrexone. Topiramate is a promising new agent and requires further study. Disulfiram, while very effective in compliant patients, presents challenges in terms of patient selection and side effects. For patients with hepatic impairment, acamprosate is a good choice.

Disulfiram Induced Reversible Hypertension: A Prospective Case Study and Brief Review

“…[14] Hypertension may be a clinically significant, dose-dependent and usually reversible side-effect of DSF therapy. [1516] In our opinion, an index of suspicion for vascular side-effects of DSF in cases with the comorbid alcohol and tobacco dependence may detect and also prevent misdiagnosis of essential hypertension. We suggest that in detected individuals, reduction of dose may be advised along with life style modification, dietary measures, and regular monitoring of BP.…”

A study of cardiovascular complications of disulfiram-ethanol reaction

“…It can be best achieved by various behavioral approaches and with medications. [5] Drugs can be used to maintain abstinence and prevent relapse. These drugs include deterrent and anticraving drugs.…”

“…[6] Among these, disulfiram, naltrexone and acamprosate are the only approved drugs in the management of alcohol abuse. [5] Disulfiram (Antabuse), chemically diethylthiocarbamoyl or tetraethyl thiuram, is the most extensively used deterrent drug for clinical management of alcoholism since its introduction in 1948. [7,8] Disulfiram reacts with the ingested alcohol (disulfiram-ethanol reaction or DER) to promote acetaldehyde accumulation, which is responsible for the unpleasant reaction in alcoholics, thus making them intolerant to alcohol.…”

“…The effects of disulfiram are seen within 1-2 hours of ingestion, peak action at about 12 hours and effects are sustained up to 72 hours. [5] DER occurs in subjects maintained on disulfiram therapy, even if they consume a small amount of ethanol (as low as blood alcohol concentration of 5-10 mg/dL). [9] This reaction is produced during alcohol challenge test or if the subject relapses while still on disulfiram therapy (up to 2 weeks after the last dose) in spite of being advised to abstain from alcohol.…”

“…Thus, chronic alcoholics may have a chronically elevated acetaldehyde concentration in the blood, which may result in excessive increase in acetaldehyde level during the reaction leading to more severe manifestations. [5] DER can begin within 5-15 minutes after ingestion of alcohol and the duration of the reaction can vary from 30-60 minutes to several hours in more severe cases or as long as there is alcohol in the blood. [6] Disulfiram is used only in selected and wellmotivated chronic alcoholics who want to remain in a state of enforced sobriety so that supportive psychotherapeutic treatment can be applied to their best advantage.…”