loperamide

An opioid receptor agonist used to treat diarrhoea (antidiarrheal agent).
It shows no significant absorption from the gut and does not cross the blood–brain barrier when used at normal doses.
It can slow down the peristalsis for the food to slowly pass through the gut, resulting in thicker stool.
It is taken by mouth.

It acts on the μ-opioid receptors in the myenteric plexus of the colon, decreasing its activity (the tone of the longitudinal and circular smooth muscles of the intestinal wall). This increases the time material stays there, allowing more water to be absorbed from the fecal matter. It also suppresses the gastrocolic reflex (rhythmic contractions of the colon soon after eating food).

It can generally only antagonize muscarinic receptors in the peripheral nervous system.
As a substrate of P-glycoprotein, it is able to saturate P-glycoprotein (which is fully occupied with substrates and cannot transport additional molecules out of the cell) and produces euphoric effects (central opioid action) at high doses or when used with P-glycoprotein inhibitors.

P-glycoprotein is a protein of the cell membrane that pumps many foreign substances out of cells. It is an ATP-dependent efflux pump with broad substrate specificity.
It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances.
It is extensively distributed and expressed in the intestinal epithelium where it pumps xenobiotics (e.g. toxins, drugs) back into the intestinal lumen, in liver cells where it pumps them into bile ducts, in the cells of the proximal tubule of the kidney where it pumps them into urinary filtrate (in the proximal tubule), and in the capillary endothelial cells composing the blood–brain barrier and blood–testis barrier, where it pumps them back into the capillaries.

(Indications)
• short-term diarrhoea
• irritable bowel syndrome (IBS)
Limited use:
• recurring or longer lasting diarrhoea
• inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• short bowel syndrome

(Side effects)
• abdominal pain
• constipation
• sleepiness
• vomiting
• dry mouth
• increased risk of toxic megacolon

(Contraindications)
• children under 12 years old: Unless otherwise prescribed by their doctor.
• high fever
• blood in stool (hematochezia): Blood in the stool and high fever can be signs of dysentery.
• mucus in stool
• rebound constipation
• during pregnancy or when trying to get pregnant
• for breast-feeding mothers
• allergy to this drug
• liver problems

(Drug interactions)
• As a substrate of P-glycoprotein, the concentration increases when given with a P-glycoprotein inhibitor (e.g. quinidine, ritonavir, ketoconazole), potentially resulting in producing central morphine-like effects by its crossing the blood–brain barrier.
• As capable of decreasing the absorption of some other drugs (e.g. saquinavir), their concentrations decrease when it is given.
• As an antidiarrheal agent, that decreases the peristalsis, when combined with other antimotility drugs (e.g. other opioids, antihistamines, antipsychotics, and anticholinergics), the risk of constipation is increased.

Cf. diphenoxylate