A 58-year-old man with oesophageal cancer has severe neuropathic pain despite high-dose morphine. The palliative care team considers rotating to methadone. Which property BEST explains methadone's advantage in neuropathic cancer pain and opioid-tolerant patients?

• A Pure mu-opioid receptor agonist with no active metabolites
• B Dual action as a mu-opioid receptor agonist and NMDA receptor antagonist ✓
• C High oral bioavailability and short half-life enabling rapid titration
• D Primary action as a kappa-opioid receptor agonist with minimal respiratory depression

Explanation

Methadone's NMDA receptor antagonism contributes to its efficacy in neuropathic pain and helps counteract opioid tolerance, distinguishing it from pure mu agonists. It has a long, not short, half-life, making titration slow and requiring expertise. It is primarily a mu agonist, not a kappa agonist, and does have active metabolites, though these are not the basis of its unique advantage.

Reference: Oxford Textbook of Palliative Medicine, 6th ed.

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Written and medically reviewed by the StethoPrep medical team.