A patient with chronic cancer pain on oral morphine develops opioid-induced constipation (OIC) that does not respond to laxatives. The physician prescribes methylnaltrexone. The key pharmacological property that makes methylnaltrexone effective for OIC without reversing analgesia is:
- A It is selective for kappa-opioid receptors in the gut and does not block mu receptors in the brain
- B It is metabolised to an active mu-agonist metabolite in the CNS that maintains analgesia
- C It is a peripherally restricted mu-opioid antagonist that does not cross the blood-brain barrier due to its quaternary ammonium structure ✓
- D It selectively inhibits 5-HT4 receptors in the gut, promoting prokinetic motility independent of opioid receptors
Correct answer: C. It is a peripherally restricted mu-opioid antagonist that does not cross the blood-brain barrier due to its quaternary ammonium structure
Explanation
Methylnaltrexone is a quaternary ammonium derivative of naltrexone. The permanent positive charge prevents it from crossing the blood-brain barrier (unlike tertiary amine naltrexone), so it selectively blocks peripheral mu-opioid receptors in the enteric nervous system. This reverses opioid-induced reduction in gut motility and secretion, relieving OIC, without penetrating the CNS to antagonise the analgesic or mood effects of centrally acting opioids. Alvimopan works similarly. Neither acts on kappa or 5-HT4 receptors.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.