Loperamid

Loperamid is a synthetic opioid receptor agonist used as an antidiarrheal. It acts primarily on mu-opioid receptors in the enteric nervous system, reducing gastrointestinal motility, increasing intestinal transit time, and allowing more water absorption.

Because of limited ability to cross the blood-brain barrier, loperamid provides anti-diarrheal effects with minimal central effects at usual doses. It is mainly administered orally and is widely available as an over-the-counter medicine in many countries. Dosing typically starts after a loose stool, with adjustments based on response, under label directions; maximal daily doses vary by country and product.

Uses include short-term relief of acute nonspecific diarrhea and the management of chronic diarrhea in some conditions such as irritable bowel syndrome with diarrhea (IBS-D) under medical supervision.

Pharmacokinetics: Loperamid is poorly absorbed and undergoes extensive first-pass metabolism in the liver, with excretion mainly in feces. It is a substrate for P-glycoprotein, which limits CNS penetration. It is metabolized by CYP3A4 and CYP2C8.

Safety: Common adverse effects are constipation, abdominal cramps, nausea, or dizziness. Serious risks include severe constipation, toxic megacolon in susceptible patients, and, with excessive dosing or combined CNS-active substances, potential cardiac conduction abnormalities. It should not be used in diarrhea caused by bacterial infections with fever or blood in stool, or in intestinal obstruction. Use in young children is restricted in many countries. Caution in hepatic impairment.

Interactions and regulation: Increases in exposure can occur with potent CYP3A4 inhibitors or P-gp inhibitors, which may raise the risk of CNS effects or heart rhythm problems. Loperamid products are OTC medicines in many places but may require prescription for higher-dose formulations in some jurisdictions.