Loperamide: a pharmacological review

Rev Gastroenterol Disord. 2007;7 Suppl 3:S11-8.

Abstract

Loperamide is an antidiarrheal medication approved for the control of diarrhea symptoms and is available without a prescription. Loperamide works by a number of different mechanisms of action that decrease peristalsis and fluid secretion, resulting in longer gastrointestinal transit time and increased absorption of fluids and electrolytes from the gastrointestinal tract. It is a phenylpiperidine derivative with a chemical structure similar to opiate receptor agonists such as diphenoxylate and haloperidol. It was designed to maintain the antidiarrheal activity of these drugs, but minimize the negative aspects associated with their effects on the opiate receptor. Because of loperamides's low oral absorption and inability to cross the blood-brain barrier, it has minimal central nervous system effects. It also has a longer duration of action than diphenoxylate. However, it has no clinically significant analgesic activity and does not decrease the pain associated with some forms of irritable bowel syndrome and diarrhea. Loperamide is metabolized by the cytochrome P450 (CYP) system and is a substrate for the CYP3A4 isoenzyme. Concurrent administration with CYP3A4 inhibitors may elevate loperamide concentrations. Common adverse reactions to loperamide include cramps and nausea. Loperamide is an effective treatment for patients with painless diarrhea and is considered to be free of abuse potential.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidiarrheals / administration & dosage
  • Antidiarrheals / chemistry
  • Antidiarrheals / pharmacokinetics
  • Antidiarrheals / pharmacology*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Drug Interactions
  • Gastrointestinal Transit / drug effects
  • Humans
  • Intestinal Absorption / drug effects
  • Loperamide / administration & dosage
  • Loperamide / chemistry
  • Loperamide / pharmacokinetics
  • Loperamide / pharmacology*
  • Peristalsis / drug effects

Substances

  • Antidiarrheals
  • Cytochrome P-450 Enzyme Inhibitors
  • Loperamide
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human