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Disulfiram treatment of alcoholism

Disulfiram will produce an aversive reaction with ethanol, usually at a dose between 250 mg/day and 500 mg/day, although some patients may not have an aversive reaction at this level. Cardiac, hepatic, and neurologic toxicity can also occur within this dosage range. If disulfiram is to be used, the …

Review

. 1990 Jun;88(6):647-55.

doi: 10.1016/0002-9343(90)90534-k.

Disulfiram treatment of alcoholism

C Wright  1 , R D Moore

Affiliations

Affiliation

1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

PMID: 2189310

DOI: 10.1016/0002-9343(90)90534-k

Free article Review

Disulfiram treatment of alcoholism

C Wright et al. Am J Med. 1990 Jun.

Free article

. 1990 Jun;88(6):647-55.

doi: 10.1016/0002-9343(90)90534-k.

Authors

C Wright  1 , R D Moore

Affiliation

1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

PMID: 2189310

DOI: 10.1016/0002-9343(90)90534-k

Erratum in

Am J Med 1991 Oct;91(4):446

Abstract

Purpose: For 40 years, disulfiram has been the alcohol-aversive drug used most frequently by American physicians in the treatment of alcohol dependency disorders. We reviewed the clinical literature regarding the risks, benefits, indications, and efficacy of this controversial drug and summarized current knowledge of this therapy. Conclusions: Disulfiram will produce an aversive reaction with ethanol, usually at a dose between 250 mg/day and 500 mg/day, although some patients may not have an aversive reaction at this level. Cardiac, hepatic, and neurologic toxicity can also occur within this dosage range. If disulfiram is to be used, the patient must clearly understand the risks of drinking while taking the drug, and the physician and patient must agree about the need for continued clinical supervision and monitoring for efficacy and side effects. The physician must also recognize that disulfiram is only an adjunctive therapy and that continued support, supervision, and other therapeutic measures are required. Disulfiram is probably effective in reducing the frequency of alcohol consumption in the compliant patient over the short term (e.g., 6 months). Certain subgroups of patients, such as those who are older, those who are more socially stable, and those who are well-motivated, may experience a beneficial effect for longer periods. The drug may be most effective in reducing short-term alcohol consumption when the compliance of the patient is supervised, although consideration of this kind of therapy includes the practical problems of supervising the patient and concerns that the supervising person may be placed in a difficult position. Prescription of disulfiram without accompanying education, counseling, and concomitant alcoholism therapy is not beneficial. Disulfiram has no proven effect on the long-term outcome of alcoholism.

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Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, ...

Yonsei Med J. 2006 Apr 30; 47(2): 167–178.

Published online 2006 Apr 30. doi: 10.3349/ymj.2006.47.2.167

PMCID: PMC2687624 PMID: 16642544

Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

Young-Chul Jung and Kee Namkoong

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Abstract

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence. These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.

Keywords: Alcohol dependence, pharmacotherapy, naltrexone, acamprosate

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INTRODUCTION

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environment factors.1 Over the last 20 years, there has been considerable progress in efforts to reduce the enormous alcohol related costs to society, such as traffic accidents in which the driver is intoxicated, and to set boundaries for injudicious alcohol use in Korea. These socio-cultural changes have probably been successful in lowering the prevalence of alcohol abuse but the prevalence of alcohol dependence seems to have been less affected.2 In a recent Korean epidemiological study,3 it was established that 10.20% of the adult population has a lifetime prevalence of alcohol dependence (15.97% of men and 4.64% of women) which makes alcohol dependence the second most common psychiatric disorder in Korea.

Treating alcohol dependence usually consists of two phases: detoxification and rehabilitation. The initial detoxification stage deals with acute withdrawal symptoms. The later rehabilitation stage attempts to prevent relapse and develops a lifestyle compatible with long-term abstinence. Whereas detoxification is widely accepted as a pharmacotherapeutic domain, rehabilitation, in clinical practice, has traditionally involved psychosocial and psychotherapeutic interventions consisting of individual and group psychotherapy, cognitive-behavioral treatments, and self-directed groups such as Alcoholics Anonymous. Although psychosocial treatments have shown effectiveness in reducing alcohol consumption and maintaining abstinence, 40 to 70% of patients still relapse to drinking within a year following treatment.4 As a part of the efforts to improve the treatment outcomes for alcohol dependence, pharmacotherapy is being investigated as another modality to enhance abstinence and prevent relapse, complementing psychosocial interventions.

The rationale of using pharmacotherapy for alcohol dependence is based on several premises.5,6 First, advances in neurobiology have identified the neurobehavioral effects of alcohol and their associated neurotransmitter systems which are related to the development of dependence and, at the same time, are potential targets for pharmacological approaches. Second, recent genetic studies have confirmed that alcohol dependence is a heterogeneous condition. While some gene variations predispose people to alcohol dependence, others confer protection. Third, animal models of alcohol dependence relapse have demonstrated that pharmacologic agents can reduce alcohol consumption and have proven to be fairly predictive of similar responses in human patients. Fourth, medications have improved the treatment of other addictive disorders such as bupropion for nicotine dependence and methadone for heroin dependence, encouraging pharmacotherapies for the treatment of alcohol dependence.

To date, three medications - disulfiram, naltrexone, and acamprosate - have been approved by the U.S. Food and Drug Administration (FDA) for treatment of alcohol dependence (Table 1). Only about 20% of eligible patients receive them, however.7 Unfortunately, medications are still disparaged as a "crutch" and some still stick to the old adage, "You can't treat a drug problem with a drug."8

Table 1

Medications for Relapse Prevention of Alcohol Dependence

SSRI, Serotonin-Specific Reuptake Inhibitor.

This article discusses (1) the neurobiological basis of alcohol dependence; (2) the efficacy and safety of disulfiram, naltrexone and acamprosate, the approved pharmacotherapies for alcohol dependence; (3) the ongoing issues for improving the effectiveness of pharmacotherapy, and (4) the novel pharmacotherapies currently under investigation.

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Medications for Treating Alcohol Dependence

Medications for treating alcohol dependence primarily have been adjunctive interventions, and only three medications--disulfiram, naltrexone, and acamprosate--are approved for this indication by the U.S. Food and Drug Administration. Disulfiram, an aversive agent that has been used for more than 40 years, has significant adverse effects and compliance difficulties with no clear evidence that it increases abstinence rates, decreases relapse rates, or reduces cravings. In contrast, naltrexone, an anticraving agent, reduces relapse rates and cravings and increases abstinence rates. Acamprosate also reduces relapse rates and increases abstinence rates. Serotonergic and anticonvulsant agents promise to play more of a role in the treatment of alcohol dependence. Although not approved by the U.S. Food and Drug Administration for this indication, the anticonvulsant topiramate and several serotonergic agents (e.g., fluoxetine, ondansetron) have been shown in recent studies to increase abstinence rates and decrease drinking.

Medications for Treating Alcohol Dependence

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STEVEN H. WILLIAMS, PH.D.

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2005;72(9):1775-1780

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A more recent article on medications for alcohol use disorder is available.

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Medications for treating alcohol dependence primarily have been adjunctive interventions, and only three medications—disulfiram, naltrexone, and acamprosate—are approved for this indication by the U.S. Food and Drug Administration. Disulfiram, an aversive agent that has been used for more than 40 years, has significant adverse effects and compliance difficulties with no clear evidence that it increases abstinence rates, decreases relapse rates, or reduces cravings. In contrast, naltrexone, an anticraving agent, reduces relapse rates and cravings and increases abstinence rates. Acamprosate also reduces relapse rates and increases abstinence rates. Serotonergic and anticonvulsant agents promise to play more of a role in the treatment of alcohol dependence. Although not approved by the U.S. Food and Drug Administration for this indication, the anticonvulsant topiramate and several serotonergic agents (e.g., fluoxetine, ondansetron) have been shown in recent studies to increase abstinence rates and decrease drinking.

Almost one third of Americans consume enough alcohol to be considered at risk for alcohol dependence, and alcohol abuse and dependence are associated with more than 100,000 deaths from alcohol-related diseases and injuries each year. The economic cost of alcohol abuse and dependence was estimated at more than $184 billion for 1998.1 Use of screening tools and brief primary care interventions for alcohol problems significantly reduces drinking levels in “problem drinkers” who are not yet alcohol dependent.2 Counseling and 12-step structured treatment programs have been the mainstays of alcohol dependence treatment, whereas pharmacologic treatments traditionally have played an adjunctive role.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

EnlargePrint

Naltrexone (Trexan) and acamprosate (Campral) are recommended as FDA-approved options for treatment of alcohol dependence in conjunction with behavior therapy. A 5

Disulfiram (Antabuse) does not increase abstinence rates or decrease relapse rates or cravings compared with placebo, and it is not recommended for routine use in primary care. B 6

Fluoxetine (Prozac) and other SSRIs are recommended for patients with comorbid depressive disorders. B 13,14

Topiramate (Topamax) and ondansetron (Zofran) are recommendedto reduce drinking frequency and increase abstinence. B 3,4

. .

To date, three medications—disulfiram (Antabuse), naltrexone (Trexan), and acamprosate (Campral)—have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence, and only about 20 percent of eligible patients receive them. In the past decade, however, there has been a growing body of evidence supporting a more central role for medications in the treatment of alcohol dependence. These medications, the evidence supporting them, and recommended dosages are discussed in the following. 3,4 provides a summary of the medications with prescribing information, adverse effects, contraindications, and costs.

TABLE 1

Medications for Treatment of Alcohol Dependence

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Acamprosate (Campral) Yes 333-mg enteric coated tablets Adults ≥ 132 lbs (60 kg): two tablets three times per day Diarrhea, headache, flatulence, nausea, vomiting, dyspepsia Severe renal impairment (creatinine clearance < 30 mL per minute [0.5 mL per second]) To avoid adverse gastrointestinal effects, initial dosing usually is at one half the given dosages with an increase of one tablet to the daily dosage each week. $125

Adults < 132 lbs: two tablets with the morning meal, one with the midday meal, and one with the evening meal

Disulfiram (Antabuse) Yes Begin with 250 mg once per day; increase to 500 mg once per day. Disulfiram–alcohol interaction: palpitations, flushing, nausea, vomiting, headache Alcohol, metronidazole (Flagyl), or paraldehyde use psychosis; cardiovascular disease Initiate only after patient has abstained from alcohol for at least 12 hours. 42

Not generally recommended for treating alcohol dependence in the primary care setting

Patient should carry an identification card describing the disulfiram–alcohol interaction.

Monitor liver function tests for hepatotoxicity.

Fluoxetine (Prozac) No Begin with 20 mg per day; may increase to 60 mg per day as needed. Nausea, headache, sedation, anxiety, sexual dysfunction Use of an MAOI, mesoridazine (Serentil), or thioridazine (Mellaril) Recommended only in patients with comorbid depression 127 (79 to 89 generic)

Nalmefene (Revex) No Available only in an injectable form (outside of research) to treat opiate overdose. Nausea, tachycardia, vasodilation, dizziness, headache, chills, vomiting None — 62 (for 2 mL [2 mg])

Naltrexone (Trexan) Yes 50 mg once per day Nausea, headache, anxiety, sedation Narcotic use, acute opioid withdrawal, acute hepatitis, liver failure Monitor liver function tests for hepatotoxicity. 205 (128 to 137 generic)

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