A 30-year-old woman with acute infective diarrhoea takes loperamide and notices her stools firm within hours but feels no central opioid effects such as euphoria or sedation. The pharmacokinetic property responsible for this separation of effects is:
- A Poor penetration across the blood-brain barrier due to P-glycoprotein efflux ✓
- B Extensive first-pass metabolism to an inactive glucuronide
- C Rapid plasma protein binding that prevents CNS distribution
- D Selective affinity for peripheral kappa-opioid receptors only
Correct answer: A. Poor penetration across the blood-brain barrier due to P-glycoprotein efflux
Explanation
Loperamide is a mu-opioid receptor agonist acting on enteric neurons to increase segmental contraction, slow transit, and raise anal sphincter tone. It has high affinity for P-glycoprotein at the blood-brain barrier, which actively pumps it out of the CNS, so therapeutic doses produce no central opioid effects. It is not a kappa-selective agent, and its action is not explained by first-pass metabolism or protein binding.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.