Loperamide-anti-diarrheal drug

Loperamide

Pharmacodynamics

Loperamide is a synthetic anti-diarrheal indicated for the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease. Loperamide is also indicated for reducing the volume of discharge from ileostomies. In man, Loperamide prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed. Loperamide is an opioid receptor agonist and acts on the mu opioid receptors in the myenteric plexus large intestines; it does not affect the central nervous system like other opioids. It works specifically by decreasing the activity of the myenteric plexus which decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall. 

Mechanism of action

In vitro and animal studies show that Loperamide acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. Loperamide inhibits peristaltic activity by a direct effect on the circular and longitudinal muscles of the intestinal wall. It is a non-selective calcium channel blocker and binds to opioid mu-receptors. Evidence also suggests that at higher concentrations it binds to calmodulin.

Protein binding

97%

Metabolism

Hepatic

Route of elimination

Excretion of the unchanged loperamide and its metabolites mainly occurs through the feces.

Half life

9.1 to 14.4 hours (average 10.8 hours)

Toxicity

Oral, mouse: LD50 = 105 mg/kg. Symptoms of overdose include constipation, drowsiness, lethargy, and nausea.

Drug drug interaction

loperamide + amprenavir= Coadministration with drugs that enhance the gastrointestinal absorption or inhibit the metabolism of loperamide 

loperamide + atazanavir = Coadministration with drugs that enhance the gastrointestinal absorption or inhibit the metabolism of loperamide

ranitidine + loperamide = Coadministration with drugs that enhance the gastrointestinal absorption or inhibit the metabolism of loperamide

bepridil + loperamide = Coadministration with drugs that inhibit the P-glycoprotein (P-gp) efflux transporter may increase the concentrations of loperamide in plasma and central nervous system (CNS). 

Therapeutic uses

Loperamide slows the rhythm of digestion so that the small intestines have more time to absorb fluid and nutrients from the foods you eat. 

Reference- Tripathi KD "Essential of medical pharmacology" 7th edition, page no- 686,687