4.4 Pharmacotherapy for Alcohol & Nicotine Use Disorders

Pharmacotherapy for Alcohol & Nicotine Use Disorders

Alcohol Use Disorder (AUD) Pharmacotherapy Overview

Pharmacotherapy plays a vital role in the comprehensive management of Alcohol Use Disorder (AUD), working synergistically with psychosocial interventions (e.g., Cognitive Behavioral Therapy, 12-step mutual aid groups). Three medications are currently FDA-approved for AUD: Naltrexone, Acamprosate, and Disulfiram. Selecting the appropriate agent requires evaluating patient recovery goals (abstinence vs. reduction in heavy drinking), hepatic function, renal clearance, and medication adherence potential.

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AUD Pharmacotherapeutic Agents

1. Naltrexone (Oral ReVia / Injectable Vivitrol)

• Mechanism: Competitive antagonist at mu-opioid receptors. By blocking endogenous opioid release triggered by alcohol consumption, naltrexone reduces the euphoric "reward" of drinking and decreases alcohol craving.
• Indication & Dosing: Oral: 50 mg PO daily. Injectable: 380 mg IM gluteal injection Q4 weeks.
• Clinical Application: Effective for both total abstinence and reduction of heavy drinking (helps prevent a lapse from becoming a full relapse).
• Safety & Monitoring: Contraindicated in patients taking prescribed opioids, those in acute opioid withdrawal, or patients with acute hepatitis/liver failure. Obtain baseline liver function tests (LFTs); monitor serum transaminases periodically.

2. Acamprosate (Campral)

• Mechanism: Structural analogue of GABA that restores balance between neuronal excitation and inhibition by modulating NMDA glutamate receptors while enhancing GABA-A tone. It reduces the chronic "protracted withdrawal" distress (anxiety, insomnia, dysphoria) that triggers relapse.
• Indication & Dosing: Standard dose: 660 mg PO three times daily (TID) (two 333 mg delayed-release tablets TID).
• Clinical Application: Indicated for maintenance of abstinence in patients who have already achieved detoxification.
• Renal Dosing Precautions: Acamprosate is cleared exclusively by the kidneys and does NOT undergo hepatic metabolism.
  • Moderate Renal Impairment (CrCl 30–50 mL/min): Reduce dose to 333 mg PO TID.
  • Severe Renal Impairment (CrCl < 30 mL/min): ABSOLUTELY CONTRAINDICATED.
  • Excellent choice for patients with severe liver disease or cirrhosis where naltrexone is unsafe.

3. Disulfiram (Antabuse)

• Mechanism: Irreversible inhibitor of aldehyde dehydrogenase (ALDH), the enzyme responsible for converting acetaldehyde to acetate during alcohol metabolism.
• The Disulfiram-Alcohol Reaction: If alcohol is consumed while taking disulfiram, toxic levels of acetaldehyde accumulate rapidly in the bloodstream within 5–10 minutes, producing a severe, highly unpleasant physiological reaction: intense facial flushing, throbbing headache, nausea, severe vomiting, diaphoresis, tachycardia, chest pain, dyspnea, and hypotension.
• Dosing & Administration: 250 mg to 500 mg PO daily. Patient must refrain from alcohol for at least 12 hours prior to the first dose.
• Nursing Counseling: Disulfiram works via psychological deterrent. Patients must be educated to avoid hidden sources of alcohol (cough syrups, mouthwashes, hand sanitizers, cooking wines, aftershaves). The disulfiram-alcohol reaction can occur up to 14 days after discontinuing disulfiram due to slow enzyme regeneration.

AUD Pharmacotherapy Comparison Matrix

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Nicotine Use Disorder Pharmacotherapy

Tobacco use disorder remains the leading cause of preventable morbidity and mortality worldwide. First-line FDA-approved pharmacotherapies comprise Nicotine Replacement Therapy (NRT), Varenicline, and Bupropion SR.

1. Nicotine Replacement Therapy (NRT)

NRT delivers controlled doses of therapeutic nicotine to relieve withdrawal symptoms without exposing the patient to toxic combustion products (tar, carbon monoxide).

• Long-Acting Formulations: Nicotine Transdermal Patch (21 mg, 14 mg, 7 mg steps). Provides constant baseline nicotine levels over 16–24 hours.
• Short-Acting Formulations: Nicotine Gum, Lozenge, Inhaler, Nasal Spray (2 mg and 4 mg strengths). Selected based on time-to-first-cigarette (TTFC): if patient smokes within 30 minutes of waking, start with 4 mg strength.
• Combination NRT (Gold Standard): Combining a long-acting patch (baseline control) with a short-acting form (lozenge or gum for acute breakthrough cravings) achieves significantly higher quit rates than monotherapy.

2. Varenicline (Chantix)

• Mechanism: Partial agonist at alpha-4 beta-2 nicotinic acetylcholine receptors. Provides moderate dopamine release to alleviate nicotine craving and withdrawal, while competitively blocking smoked nicotine from binding, reducing the rewarding effect of smoking.
• Dosing Protocol: Titrated over 1 week (0.5 mg daily for 3 days, then 0.5 mg BID for 4 days, then 1 mg BID). Target quit date is set for Day 8 (or within 8–35 days of starting).
• Side Effects & Nursing Care: Take with food and a full glass of water to minimize nausea. Educate regarding potential vivid dreams or insomnia.

3. Bupropion SR (Zyban / Wellbutrin)

• Mechanism: Inhibits neuronal reuptake of norepinephrine and dopamine (NDRI), mimicking nicotine's neurochemical actions on reward pathways.
• Dosing Protocol: 150 mg PO daily for 3 days, then 150 mg PO BID (spaced at least 8 hours apart). Target quit date set after 1–2 weeks of treatment.
• Black Box Warnings & Contraindications: Contraindicated in patients with seizure disorders, current or prior diagnosis of anorexia nervosa or bulimia, or undergoing abrupt withdrawal from alcohol/sedatives (lowers seizure threshold).