Diarrhea, a condition marked by frequent loose or watery bowel movements, can be triggered by multiple factors such as viral or bacterial infections, food intolerances, anxiety, medications, and digestive disorders. Symptoms may include abdominal pain, bloating, nausea, and cramping. Severe or prolonged diarrhea can lead to complications like electrolyte imbalances, malnutrition, and dehydration if left untreated.

Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down bowel movements. They bind to opioid receptors in the gastrointestinal tract, reducing motility and fluid secretion. Loperamide (Imodium), Diphenoxylate, and Difenoxin are commonly used opioids for treating diarrhea.

Loperamide operates by activating opioid receptors in the intestine, increasing anal sphincter tone and mouth-to-cecum travel time. Its poor ability to cross the blood-brain barrier results in minimal central nervous system effects. It is readily available over-the-counter as solutions, capsules, or chewable tablets. It should be discontinued if acute diarrhea doesn't reverse in 2 days. It should not be prescribed for children below two years of age.

Diphenoxylate, another opioid, acts by reducing the movement of the intestines. Its active metabolite, difenoxin, boosts its antidiarrheal effects. To discourage misuse, diphenoxylate is often combined with atropine and is indicated for moderate to severe diarrhea. However, atropine-related anticholinergic effects like constipation, nausea, xerostomia, dry mouth, and blurred vision may also occur.

Enkephalins, endogenous opioids, inhibit intestinal secretions. Racecadotril, a prodrug, is converted to thiorphan. It is an enkephalinase inhibitor and increases enkephalin levels by inhibiting their degradation. This action reduces fluid secretion and enhances absorption in the intestine, providing antidiarrheal effects. It does not penetrate the blood-brain barrier. It is safe for treating acute diarrhea in children; however, it is not approved in the United States.

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