A patient stabilized on a full mu-opioid agonist for chronic pain is administered buprenorphine, a partial agonist at the same receptor. What is the most likely pharmacodynamic outcome?

• A Synergistic analgesia with an increased risk of serotonin syndrome
• B Reduced analgesic effect due to competitive antagonism by the partial agonist ✓
• C Enhanced respiratory depression due to allosteric potentiation
• D No significant interaction because partial agonists do not bind to opioid receptors

Explanation

A partial agonist has high receptor affinity but low intrinsic activity. When administered to a patient on a full agonist, the partial agonist displaces the full agonist but produces a submaximal response. This reduces net receptor activation, causing competitive antagonism and potentially precipitating withdrawal. Distractor A is wrong because partial agonists do not synergize with full agonists at the same receptor; they block the full agonist's effect.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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