Mechanisms of action of loperamide.

The pharmacology of loperamide is discussed, with particular reference to the drug's antidiarrhoeal properties. Its absorption, distribution, metabolism and excretion are considered and rapid concentration in the small intestine is described. The mechanism of action of loperamide on fluid and electrolyte transport is examined with reference to opiate agonism, calcium-channel blocking, calmodulin inhibition, and paracellular permeability. The colon appears to be the main site of action of loperamide on gut motility and transit. In the proximal colon, the drug accentuates segmenting motor activity. Work relating to the activity of loperamide on bacterial toxins and other secretory agents is outlined. Diarrhoea induced by prostaglandins can be prevented by pretreatment with the drug. Details are given of clinical applications of loperamide for diarrhoea control in children and adults. The drug has no significant side-effects and presents no serious threat of abuse.