What is the mechanism of action of Disulfiram (Antabuse), also known as (Antabuse) (Disulfiram)?

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From the Guidelines

Disulfiram (Antabuse®) is not recommended as a first-line treatment for alcohol use disorder due to its potential for toxic liver injury and limited efficacy in patients with liver-function abnormalities. When considering treatment options for alcohol use disorder, it is essential to prioritize medications that have demonstrated efficacy and safety in patients with liver disease. According to the 2013 clinical practice guidelines for the management of alcoholic liver disease 1, disulfiram is currently not commonly used due to its aversive therapy mechanism, which causes unpleasant symptoms such as flushing, dizziness, nausea, vomiting, arrhythmia, dyspnea, and headache when alcohol is consumed. Instead, medications like baclofen, acamprosate, and naltrexone have shown promise in maintaining abstinence and reducing cravings for alcohol. For example, baclofen has been found to effectively maintain abstinence in patients with liver cirrhosis 1, while acamprosate reduces withdrawal effects and cravings for alcohol, with a recommended dosage of 1,998 mg/day for patients with a body weight of ≥60 kg 1. Naltrexone, on the other hand, decreases the concentration of dopamine in the brain and dampens activation of the reward pathway by alcohol, but its use is not recommended in patients with ALD due to the risk of toxic liver injury 1. Key considerations when treating alcohol use disorder include:

  • Patient liver function and potential for toxic liver injury
  • Efficacy of the medication in maintaining abstinence and reducing cravings
  • Importance of combining medication with counseling and behavioral interventions
  • Need for careful patient selection and monitoring to minimize adverse effects.

From the FDA Drug Label

Disulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage During alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. One (or even two) weeks after a patient has taken his last dose of disulfiram, ingestion of alcohol may produce unpleasant symptoms. The patient will experience a disulfiram-alcohol reaction if they ingest alcohol while taking Disulfiram, which can persist as long as alcohol is being metabolized.

  • The reaction is proportional to the dosage of both disulfiram and alcohol.
  • Prolonged administration of disulfiram does not produce tolerance; the patient becomes more sensitive to alcohol over time 2.

From the Research

Disulfiram (Antabuse®) Overview

  • Disulfiram is a medication approved for the treatment of alcohol use disorder [(3,4,5)].
  • It works by deterring alcohol consumption, as it causes unpleasant reactions when alcohol is consumed 6.

Efficacy of Disulfiram

  • Studies have shown that disulfiram is effective in reducing alcohol consumption and increasing abstinence days [(4,6,7)].
  • A meta-analysis found that disulfiram was effective only when intake was supervised 4.
  • A randomized, multicentre, open-label, comparative trial found that supervised disulfiram was more effective than naltrexone and acamprosate in reducing heavy drinking days and increasing abstinence days 7.

Safety and Tolerability

  • Disulfiram has a unique safety profile that needs to be balanced with the treatment objective and individual patient preferences 3.
  • Safety considerations include the impact of concurrent alcohol consumption, multiple physical comorbidities, and concomitant medication 3.
  • A review of disulfiram literature found that supervised intake of disulfiram has proven to be an effective and safe adjunct to biopsychosocial alcoholism therapy 6.

Comparison with Other Medications

  • Disulfiram has been compared to other medications, including naltrexone and acamprosate, in several studies [(4,6,7)].
  • A meta-analysis found that acamprosate and naltrexone were more effective than disulfiram in supporting continuous abstinence 4.
  • However, a randomized, multicentre, open-label, comparative trial found that supervised disulfiram was more effective than naltrexone and acamprosate in reducing heavy drinking days and increasing abstinence days 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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