Loperamide/simethicone Loperamide/simethicone Loperamide/simethicone is combination medication marketed under the trade name Imodium Multi-Symptom Relief (formerly Imodium A-D Advanced) used to treat diarrhea and gas simultaneously. It is manufactured by the McNeil Consumer Healthcare Division of McNeil PPC, Inc. Loperamide is a μ-opioid receptor agonist that works in the intestines. Although it is an opioid, it has no effects on the central nervous system. It reduces diarrhea by slowing the transit time of contents through the intestinal tract thereby allowing more water to be reabsorbed from the intestinal lumen. Simethicone reduces gas by allowing smaller gas bubbles to coalesce into larger bubbles
Loperamide first-pass metabolism by the liver. Loperamide metabolizes into an MPTP-like compound, but is unlikely to exert neurotoxicity. Efflux by P-glycoprotein also prevents circulating loperamide from effectively crossing the blood–brain barrier, so it can generally only antagonize muscarinic receptors in the peripheral nervous system, and currently has a score of 1 on the anticholinergic cognitive burden scale. Concurrent administration of P-glycoprotein inhibitors such as quinidine potentially allows loperamide to cross the blood–brain barrier and produce central morphine-like effects. Loperamide taken with quinidine was found to produce respiratory depression, indicative of central opioid action. Loperamide has been shown to cause a mild