Disulfiram (Antabuse):

Antabuse (Disulfiram): Overview
​Antabuse (disulfiram) is a medication used to support the treatment of alcohol use disorder (AUD) by discouraging alcohol consumption through unpleasant physiological reactions.

Mechanism of Action
  • Disulfiram inhibits aldehyde dehydrogenase (ALDH), an enzyme involved in metabolizing alcohol.
  • When alcohol is consumed, it is broken down into acetaldehyde by alcohol dehydrogenase (ADH). Normally, ALDH converts acetaldehyde into acetic acid, a harmless substance.
  • Disulfiram blocks ALDH, leading to the accumulation of acetaldehyde in the blood. Elevated acetaldehyde levels cause severe discomfort, reinforcing abstinence.
Clinical Benefits
  1. Primary Use:
    • Supports abstinence in individuals with AUD by creating a strong deterrent against drinking.
  2. Behavioral Reinforcement:
    • Functions as a psychological and physical barrier to alcohol consumption.
    • Best used in combination with psychosocial support or therapy to improve long-term outcomes.
  3. Adjunctive Role:
    • Not a standalone cure for AUD but enhances the effectiveness of a comprehensive treatment plan.

Dosage
  1. Typical Dosing:
    • Initial dose: 500 mg once daily for 1–2 weeks.
    • Maintenance dose: 250 mg once daily (range: 125–500 mg daily).
  2. Administration:
    • Taken orally.
    • Must be initiated after a period of alcohol abstinence (at least 12–48 hours).
  3. Duration of Use:
    • Varies based on individual needs but typically used for weeks to months under close supervision.

Side Effects
  1. Common Side Effects:
    • Drowsiness or fatigue.
    • Metallic or garlic-like taste in the mouth.
    • Skin rash or acne.
  2. Alcohol-Disulfiram Reaction:
    • Occurs if alcohol is consumed while on disulfiram.
    • Symptoms include:
      • Flushing.
      • Nausea and vomiting.
      • Severe headache.
      • Sweating.
      • Tachycardia or palpitations.
      • Hypotension.
    • In severe cases, reactions can be life-threatening (e.g., respiratory distress or cardiovascular collapse).
  3. Serious Side Effects:
    • Hepatotoxicity (requires liver function monitoring).
    • Peripheral neuropathy (tingling or numbness in extremities).
    • Psychotic symptoms (rare).

Prevalence of Side Effects
  • Mild side effects (e.g., drowsiness, metallic taste) are relatively common but manageable.
  • Severe adverse reactions (e.g., liver damage) are rare but necessitate caution in patients with pre-existing liver disease.
  • The alcohol-disulfiram reaction occurs reliably when alcohol is consumed, reinforcing its deterrent effect.

Key Considerations
  1. Contraindications:
    • Severe cardiac disease.
    • Psychosis.
    • Chronic liver disease or cirrhosis.
    • Recent alcohol use (within 12–48 hours).
  2. Monitoring:
    • Regular liver function tests (LFTs).
    • Monitor for signs of neuropathy or severe reactions.
  3. Counseling:
    • Patients must be educated about avoiding all sources of alcohol, including in medications, mouthwashes, or food.
  4. Pregnancy and Lactation:
    • Not recommended during pregnancy or while breastfeeding unless benefits outweigh risks.

Clinical Effectiveness
  • Disulfiram is most effective in highly motivated individuals or those under supervised treatment.
  • Works best when combined with counseling, behavioral therapy, and peer support programs like Alcoholics Anonymous (AA).
  • Long-term adherence can be challenging, and relapse is possible upon discontinuation.
Antabuse is a potent deterrent against alcohol consumption but requires close medical supervision and commitment from the patient for optimal outcomes.-

Sources