A patient on buprenorphine for opioid use disorder requires emergency surgery with fentanyl for analgesia. Which pharmacological principle explains why high-dose fentanyl may be ineffective and what is the management?

• A Buprenorphine induces CYP3A4, rapidly metabolizing fentanyl to inactive norfentanyl
• B Buprenorphine's very high receptor affinity and slow receptor dissociation (partial agonist with ceiling for analgesia) occupy mu receptors, limiting fentanyl access; manage with high-dose ketamine, regional anesthesia, or continuing buprenorphine and adding non-opioid multimodal analgesia ✓
• C Buprenorphine upregulates mu-opioid receptors causing tolerance to fentanyl
• D Buprenorphine activates kappa receptors causing dysphoria that antagonizes fentanyl analgesia

Explanation

Buprenorphine is a partial mu-opioid agonist with extremely high affinity (sub-nanomolar Ki) and very slow receptor dissociation kinetics (off-rate). At standard opioid use disorder doses, it occupies 80–95% of mu receptors. Its tight binding prevents full agonists like fentanyl from displacing it at normal doses, requiring very high fentanyl doses to compete — raising overdose risk. Preferred approaches include: continuing buprenorphine throughout and providing supplemental non-opioid analgesia (ketamine infusions, regional blocks, NSAIDs, acetaminophen), or in some protocols, converting to full agonist perioperatively with opioid monitoring.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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