Naloxegol (a peripherally acting mu-opioid receptor antagonist, PAMORA) is used for opioid-induced constipation without reversing central analgesia because:

• A Naloxegol has higher affinity for enteric μ-opioid receptors than CNS μ-receptors
• B Naloxegol is PEGylated and is a P-glycoprotein substrate, limiting its CNS penetration while maintaining gut activity ✓
• C Naloxegol selectively inhibits δ-opioid receptors in the myenteric plexus without affecting μ-receptors centrally
• D Naloxegol undergoes complete first-pass metabolism into the μ-active form only in the gut wall

Explanation

Naloxegol is a PEGylated derivative of naloxone. PEGylation makes it a substrate for P-glycoprotein (P-gp) efflux transporters at the blood-brain barrier; active P-gp efflux limits its CNS penetration. In the GI tract (which lacks a significant P-gp barrier), naloxegol freely antagonises enteric μ-opioid receptors, reversing opioid-induced reduction in intestinal motility and secretion. This selectivity allows restoration of bowel function without compromising pain control.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.