Pharmacotherapy for Substance Use Disorders

OUD Pharmacotherapy - Opioid Knock Out

• Opioid Antagonists: Block opioid effects. For relapse prevention or overdose reversal.

• Naltrexone (ReVia, Vivitrol)

  • Mechanism: µ-opioid receptor antagonist. Blocks opioid euphoria & psychoactive effects.
  • Use: OUD relapse prevention (after detoxification); also for Alcohol Use Disorder (AUD).
  • Initiation: Must be opioid-free for 7-10 days (e.g., heroin) or 10-14 days (e.g., methadone) to prevent precipitated withdrawal.
    • Consider Naloxone challenge test.
  • Dosing:
    • Oral: 50 mg/day.
    • LAI (Vivitrol): 380 mg IM q4wks.
  • ⚠️ Caution: Hepatotoxicity (monitor LFTs). Avoid in acute hepatitis/liver failure.
  • 📌 Mnemonic: "Nal-TREX-one": TREX (T-Rex) powerfully blocks; ONE for once daily (oral) or once monthly (LAI).

• Naloxone (Narcan)

  • Mechanism: Rapid, potent opioid antagonist. Reverses overdose by displacing opioids.
  • Use: Emergency treatment of opioid overdose.
  • Admin: IV, IM, SC, Intranasal. Rapid onset (1-5 min).
  • Key Point: Short half-life (30-90 min); repeated doses often needed for sustained reversal.

  ⭐ Naloxone administration can precipitate acute, severe withdrawal symptoms in opioid-dependent individuals.

AUD Pharmacotherapy - Booze Blues Busters

• Goal: Reduce relapse, cravings, and alcohol consumption.
• Key Meds (📌 NAD): Naltrexone, Acamprosate, Disulfiram. First-line: Naltrexone, Acamprosate. Disulfiram for select motivated patients.

• Naltrexone (ReVia, Vivitrol)

  • Mechanism: μ-opioid antagonist. ↓ rewarding effects, ↓ cravings.
  • Dose: Oral 50 mg OD; IM depot 380 mg q4wks.
  • ⚠️ CI: Current opioid use (precipitates withdrawal - ensure 7-10 days opioid-free), acute hepatitis, liver failure. Monitor LFTs.

• Acamprosate (Campral)

  • Mechanism: NMDA receptor modulator; restores GABA/glutamate balance.
  • Dose: 666 mg TID (adjust for renal impairment).
  • Use: Maintains abstinence. Effective post-detoxification.
  • ✅ Preferred in liver disease (renal excretion).
  • ⚠️ CI: Severe renal impairment (CrCl < 30 mL/min).

• Disulfiram (Antabuse)

  • Mechanism: Aldehyde dehydrogenase inhibitor → acetaldehyde accumulation if alcohol consumed.
  • Dose: 125-250 mg OD (max 500 mg).
  • Use: Aversion therapy; requires high motivation & supervision.
  • ⚠️ CI: Cardiac disease, psychosis, pregnancy, metronidazole. Avoid ALL alcohol forms.
  • 📌 DER (Disulfiram-Ethanol Reaction): Flushing, N/V, palpitations, hypotension.

⭐ Acamprosate is generally considered safe in patients with liver disease as it is primarily excreted renally and not metabolized by the liver.

Tobacco & Benzo Rx - Puff, Pills, Peace

• First-line Agents for Smoking Cessation:

  • Nicotine Replacement Therapy (NRT):
    • Forms: Patch, gum, lozenge, inhaler, spray.
    • Dosing: Patch (21mg, 14mg, 7mg taper); Gum (2mg if <25 cigs/day, 4mg if ≥25 cigs/day).
    • 💡 Combine patch (long-acting) + short-acting form (gum, lozenge) for breakthrough cravings.
  • Varenicline:
    • MOA: Partial nicotinic receptor agonist.
    • Dose: Start 0.5mg OD → 1mg BD (target 12 wks). Start 1 week before quit date.
    • 💡 Highest monotherapy efficacy for smoking cessation.
    • SE: Nausea, insomnia. ⚠️ Rare neuropsychiatric side effects; monitor.
  • Bupropion (SR):
    • MOA: Norepinephrine-Dopamine Reuptake Inhibitor (NDRI).
    • Dose: 150mg OD → 150mg BD (7-12 wks). Start 1-2 weeks before quit date.
    • 💡 Also aids in reducing post-cessation weight gain.
    • CI: Seizure disorder, eating disorder (bulimia/anorexia), MAOI use within 14 days.

• 📌 Smoking Cessation First-Line: Never Vape Bupropion! (NRT, Varenicline, Bupropion).

• Benzodiazepine (BZD) Withdrawal Management:

  • Principle: Gradual taper using a long-acting BZD.
    • Agents: Diazepam (preferred), Chlordiazepoxide.
    • Taper: Reduce daily dose by 10-25% every 1-2 weeks.
    • 💡 CIWA-B scale can guide symptom-triggered therapy or adjust fixed taper.
  • Adjuncts for symptomatic relief:
    • Propranolol (for autonomic hyperactivity: tachycardia, tremor).
    • Anticonvulsants (e.g., Carbamazepine, Valproate) if high seizure risk or history.
  • ⚠️ Risks: Seizures, delirium, perceptual disturbances, protracted withdrawal symptoms.

⭐ Flumazenil (BZD antagonist) is generally contraindicated in chronic BZD dependence as it can precipitate acute withdrawal and seizures.

High‑Yield Points - ⚡ Biggest Takeaways

• Naltrexone: For opioid & alcohol dependence. Oral/injectable. Monitor liver function.
• Acamprosate: Maintains alcohol abstinence. Renally cleared; preferred in liver disease.
• Disulfiram: Aversive therapy for alcohol. Inhibits aldehyde dehydrogenase, causing unpleasant reaction.
• Methadone: Opioid agonist for OUD. Risk of QT prolongation and drug interactions.
• Buprenorphine: Partial opioid agonist for OUD. Ceiling effect on respiratory depression; safer in overdose.
• Varenicline: Effective for nicotine cessation. Partial nicotinic receptor agonist.