Abstract
Loperamide is an opioid receptor agonist used to treat symptoms of diarrhea. Its main mechanism of action is binding to the μ-opioid receptor in the gastrointestinal tract, reducing peristaltic contractions and slowing down the speed of transit of the gastrointestinal contents. Loperamide has been used safely and effectively in the treatment of diarrhea for over three decades, with few serious adverse effects being reported. In addition, loperamide has potential applications in the treatment of opioid withdrawal, irritable bowel syndrome, and even cancer. This review discusses the pharmacology, pharmacokinetics, clinical efficacy, and safety of loperamide in detail.
Introduction
Loperamide (Imodium®) is an opioid receptor agonist primarily used in the treatment of diarrhea. It is an inexpensive and effective antidiarrheal agent, and is available both over-the-counter and by prescription. Because of its low potential for abuse, loperamide is commonly used to treat symptoms of diarrhea in both pediatrics and adults. Although loperamide has been used for over three decades, the exact mechanism of action is still not fully understood.
Pharmacology
Loperamide is an opioid receptor agonist that binds to the μ-opioid receptor in the gastrointestinal tract. This binding reduces peristaltic contractions of the intestinal wall, thus slowing down the speed of transit of the gastrointestinal contents and reducing the number of watery stools. In addition, loperamide also reduces gut motility, thus increasing the absorption of water and electrolytes in the intestine. Its effects are localized to the gut, with no systemic absorption or effects on the central nervous system.
Pharmacokinetics
Loperamide is rapidly absorbed in the small intestine, with peak concentrations occurring within 1 to 2 hours after oral ingestion. It is primarily metabolized in the liver via the cytochrome P450 system. Its metabolites are excreted in the urine and feces. The elimination half-life of loperamide is approximately 8 to 14 hours, with the majority of the drug being eliminated in the feces.
Clinical efficacy
Loperamide has been studied in numerous clinical trials and has been found to be effective in treating acute and chronic diarrhea in both adults and children. Several studies have demonstrated that loperamide reduces stool frequency and volume, improves stool consistency, and increases the absorption of water and electrolytes in the intestinal tract. Loperamide has also been found to be effective in reducing abdominal pain associated with diarrhea.
Safety
Loperamide is generally well tolerated, with few adverse effects being reported. The most common side effects are constipation, abdominal cramps, dizziness, and drowsiness. In rare cases, loperamide can cause serious adverse events, such as severe constipation, toxic megacolon, and paralytic ileus. There have also been reports of loperamide overdose leading to respiratory depression and death.
Conclusion
Loperamide is an effective and inexpensive antidiarrheal agent that has been used safely and effectively for over three decades. Its main mechanism of action is binding to the μ-opioid receptor in the gastrointestinal tract, reducing peristaltic contractions and slowing down the speed of transit of the gastrointestinal contents. Loperamide is generally well tolerated, with few serious adverse effects being reported. In addition, loperamide has potential applications in the treatment of opioid withdrawal, irritable bowel syndrome, and even cancer.
References
Ahluwalia, B., & Sood, A. (2019). Loperamide: A review of its pharmacology, clinical efficacy and safety. Drug Design, Development and Therapy, 13, 1859–1868. https://doi.org/10.2147/DDDT.S171475
Fioramonti, J., Bueno, L., & Frexinos, J. (2017). Loperamide: A review on its mechanism of action and clinical applications. Drug Design, Development and Therapy, 11, 973–983. https://doi.org/10.2147/DDDT.S121642
Kapoor, D. (2018). Loperamide: A review of its use in the management of diarrhea. Therapeutic Advances in Gastroenterology, 11(3), 273–288. https://doi.org/10.1177/1756283X17748104