Loperamide controls acute non-infective diarrhea effectively yet produces neither analgesia nor significant euphoria even at supratherapeutic doses taken orally. The pharmacokinetic property explaining this is:

• A Extensive first-pass metabolism to inactive glucuronides
• B Poor penetration across the blood-brain barrier due to P-glycoprotein efflux and high polarity ✓
• C Rapid renal clearance before reaching the central nervous system
• D Selective affinity for peripheral mu receptors located only in the myenteric plexus

Explanation

Loperamide is a mu-opioid receptor agonist that slows intestinal peristalsis and increases sphincter tone. It is actively pumped out of the central nervous system by P-glycoprotein, limiting brain concentrations, so it lacks central opioid effects at normal doses. At massive overdoses, P-glycoprotein saturation can permit cardiac conduction toxicity through cardiac sodium channels. Diphenoxylate, by contrast, is given with atropine to discourage misuse.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.