Review: loperamide—a potent antidiarrhoeal drug with actions along the alimentary tract

SUMMARY The synthetic opioid, loperamide, reduces stool weight, frequency of bowel movements, urgency and faecal incontinence in acute and chronic diarrhoea. In man, the mechanism of action of loperamide is primarily the retardation of small‐intestinal transit, and the stimulation of anal sphincter pressure and of faecal continence. This mechanism increases mucosal contact time, allowing more complete absorption of electrolytes and water. Studies in animals have demonstrated inhibitory effects of opiates and opioids, including loperamide, on fluid and electrolyte secretion induced by various secretagogues. By comparison, opiates have smaller if any antisecretory or pro‐absorptive actions in man. The discrepancies between the results obtained in animal and human experiments are most certainly due to the large differences between drug doses used. Besides its opiate‐receptor binding and stimulating activity, loperamide also behaves as a calcium–calmodulin antagonist and as a calcium channel blocker. These two other mechanisms might contribute to loperamide's antidiarrhoeal activity. Loperamide is more effective and safer than other opiates or opioid drugs in the treatment of both infantile and adult diarrhoea of various causes, although adequate fluid and electrolyte replacement remain the prime need.