Loperamide is an opioid used for diarrhea that does not produce central opioid effects at therapeutic doses because:

• A It is a kappa-selective agonist with no mu activity
• B It is a substrate for P-glycoprotein efflux at the blood-brain barrier, limiting CNS entry ✓
• C It is ionized at physiological pH and cannot cross lipid membranes
• D It is rapidly metabolized by first-pass effect to an inactive metabolite

Explanation

Loperamide is a mu opioid agonist but is actively pumped out of the CNS by P-glycoprotein (MDR1) at the blood-brain barrier. At standard doses, it acts only on peripheral mu receptors in the myenteric plexus, reducing gut motility. At very high doses or with P-glycoprotein inhibitors, it can enter the CNS and cause respiratory depression and euphoria.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.