Tramadol's analgesic mechanism differs from pure opioids in that it additionally acts as:
- A A selective serotonin-norepinephrine reuptake inhibitor (SNRI), contributing to descending pain inhibition independent of opioid receptor activation ✓
- B A GABA-B receptor agonist, activating inhibitory interneurons in the dorsal horn
- C An NMDA receptor antagonist, blocking central sensitization in chronic pain
- D A kappa-opioid receptor full agonist, providing spinal analgesia independent of mu-receptor
Correct answer: A. A selective serotonin-norepinephrine reuptake inhibitor (SNRI), contributing to descending pain inhibition independent of opioid receptor activation
Explanation
Tramadol has a dual mechanism: (1) weak mu-opioid receptor agonism (via its O-demethylated active metabolite M1, formed by CYP2D6), and (2) inhibition of both serotonin (SERT) and norepinephrine (NET) reuptake, augmenting descending inhibitory pain pathways. The SNRI effect explains why tramadol has analgesic efficacy in neuropathic pain where pure opioids are less effective, and why its analgesic effects are not fully reversed by naloxone. Critically, the SNRI component contributes to serotonin syndrome risk when combined with other serotonergic drugs.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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