Makindo Medical Notes

💊 Buprenorphine is a partial μ-opioid receptor agonist and κ-opioid receptor antagonist used in pain management and opioid dependence. It produces analgesia with a ceiling effect for respiratory depression, reducing overdose risk compared with full agonists like morphine. However, it still causes sedation, constipation, and dependence, and must be used cautiously in combination with other sedatives.

📘 About

• Always check the BNF entry here for up-to-date formulations and dosing.
• Used for moderate to severe pain and as part of opioid substitution therapy (OST) in dependence (often with naloxone as Suboxone®).
• Has slow receptor dissociation → long duration of action, but can make reversal with naloxone more difficult in overdose.

⚙️ Mode of Action

• Acts as a partial agonist at μ-opioid receptors → produces analgesia but with a ceiling effect on euphoria and respiratory depression.
• Acts as a weak antagonist at κ-opioid receptors → reduces dysphoria and some side effects seen with other opioids.
• At high doses, can displace full agonists (e.g. heroin, methadone) and precipitate withdrawal in dependent individuals.

💊 Indications & Doses

• Moderate–severe pain: IM or slow IV injection 200–400 micrograms every 6–8 hours.
• Premedication: 400 micrograms sublingual (SL).
• Transdermal patches:
• Butrans®: 5 micrograms/hour patch, changed every 7 days (max 2 patches at once). Apply to clean, dry, non-hairy upper torso skin; rotate sites and avoid reapplying to the same area for ≥3 weeks.
• Transtec®: 35 micrograms/hour patch, changed every 96 hours (max 2 patches). Rotate sites; avoid reapplying to the same area for ≥6 days.
• See BNF for other formulations (e.g. buccal films, sublingual tablets, depot injections for dependence).

🔄 Interactions

• Avoid concurrent use with benzodiazepines, alcohol, or other CNS depressants — risk of respiratory depression and coma.
• May potentiate effects of other opioids or sedatives.
• Use caution with CYP3A4 inhibitors (e.g. macrolides, azoles) — can ↑ plasma levels.

⚠️ Cautions

• Respiratory depression remains a key risk, especially in naïve or elderly patients — treat with airway support and naloxone if severe.
• Use cautiously in hepatic impairment (metabolised by liver) and renal failure.
• May cause precipitated withdrawal if given to patients on full μ-opioid agonists.
• Driving impairment — warn patients of legal and safety implications.

🚫 Contraindications

• Acute respiratory depression or severe COPD.
• Coma, head injury, or raised intracranial pressure.
• Paralytic ileus or severe hepatic impairment.
• Hypersensitivity to buprenorphine or patch excipients.

💥 Adverse Effects

• Common: drowsiness, dizziness, nausea, constipation, miosis, sweating.
• Serious: respiratory depression (less pronounced than morphine), confusion, hypotension.
• Prolonged use → dependence and withdrawal on cessation.
• Ceiling effect on respiratory depression limits overdose lethality relative to full agonists.

🧠 Teaching Note

Buprenorphine’s dual action as a partial μ-agonist and κ-antagonist explains both its therapeutic benefit and unique safety profile. It is often used in combination with naloxone (Suboxone®) for supervised opioid substitution to deter misuse. Because it binds tightly to opioid receptors, it can blunt the effect of other opioids for several days after use — an important consideration in acute pain management.

📚 References

• BNF: Buprenorphine
• DrugBank: Buprenorphine
• NICE NG46: Controlled drugs — safe use and management
• UKCPA Perioperative Medicines Handbook (2024)

🕓 Revisions

• 2025-10 — Expanded and annotated by Dr O’Kane (Makindo edition).