Loperamide Hydrochloride (Diar-Aid Tablets 2 Mg, Imodium Capsules 2 Mg)
Loperamide hydrochloride is an antidiarrheal agent that slows intestinal motility, affects water and electrolyte movement through intestine, inhibits peristalsis, reduces daily fecal volume, increases viscosity and bulk density of stool, and diminishes loss of fluid and electrolytes. It is indicated in the control and symptomatic relief of acute nonspecific or chronic diarrhea; and in the reduction in volume of ileostomy output.
Loperamide (Imodium, others), like diphenoxylate, is a piperidine derivative. It slows gastrointestinal motility by effects on the circular and longitudinal muscles of the intestine presumably as a result of its interactions with opioid receptors in the intestine. Some part of its antidiarrheal effect may be due to a reduction of gastrointestinal secretion. In controlling chronic diarrhea, loperamide is as effective as diphenoxylate. In clinical studies, the most common side effect is abdominal cramps. Little tolerance develops to 1 s constipating effect.
In human volunteers taking large doses of loperamide, concentrations of drug in plasma peak about 4 hours after ingestion; this long latency may be due to inhibition of GI motility and to enterohepatic circulation of the drug. The apparent elimination half-life is 7 to 14 hours. Loperamide is poorly absorbed after oral administration and, in addition, apparently does not penetrate well into the brain because of P-glycoprotein transporter widely expressed in the brain endothelium. Mice with deletions of one of the genes encoding the P-glycoprotein transporter have much higher brain levels and significant central effects after administration of loperamide. Inhibition of P-glycoprotein by many clinically used drugs, such as quinidine and verapamil, possibly could lead to enhanced central effects of loperamide.
In general, loperamide is unlikely to be abused parenterally because of its low solubility; large doses of loperamide given to human volunteers do not elicit pleasurable effects typical of opioids. The usual dosage is 4 to 8 mg / day; the daily dose should not exceed 16 mg.
Loperamide has been shown to be effective against traveler’s diarrhea, used either alone or in combination with antimicrobial agents (trimethoprim, trimethoprim-sulfamethoxazole, or a fluoroquinolone). Loperamide also has been used as adjunct treatment in almost all forms of chronic diarrheal disease, with few adverse effects. Loperamide lacks significant abuse potential and is more effective in treating diarrhea than diphenoxylate. Overdosage, however, can result in CNS depression (especially in children) and paralytic ileus. In patients with active inflammatory bowel disease involving the colon, loperamide should be used with great caution, if at all, to prevent development of toxic megacolon.
Loperamide N-oxide, an investigational agent, is a site-specific prodrug; it is chemically designed for controlled release of loperamide in the intestinal lumen, thereby reducing systemic absorption.
Loperamide (4 mg initially and not exceeding 16 mg / day) is indicated in the control and symptomatic relief of acute nonspecific diarrhea and chronic diarrhea associated with inflammatory bowel diseases. In addition, it may be used to control traveler’s diarrhea or to reduce the volume of discharge from ileostomies. The antidiarrheal agents are codeine, diphenoxylate, and atropine (Lomotil), and loperamide. Because it causes less addiction than codeine, loperamide is now the most commonly used antidiarrheal agent.
These agents achieve their effects by reducing the propulsive activity of the gut, enhancing the contact time between the intestinal mucosal and the luminal contents, and enhancing active chloride absorption, hence opposing the secretory effects of toxin. Loperamide should not be used in acute diarrhea associated with organisms that penetrate the intestinal mucosa (enteroinvasive Escherichia coli, Salmonella, and Shigella) or in pseudomembranous colitis associated with broad-spectrum antibiotics. Opioid antidiarrheal agents should not be used in cases of severe ulcerative colitis threatened by impending toxic megacolon or in patients with shigellosis, because they prolong duration of the disease.