Opioid as codeine, has similarly demonstrated little benefit in several recent studies.) Low dose morphine may help chronic cough but its use is limited by side effects. In cases of diarrhea-predominate irritable bowel syndrome, opioids may be used to suppress diarrhea. Loperamide is a peripherally selective opioid available without a prescription used to suppress diarrhea. The ability to suppress diarrhea also produces constipation when opioids are used beyond several weeks. Naloxegol, a peripherally-selective opioid antagonist is now available to treat opioid induced constipation. Opioids may help with shortness of breath particularly in advanced diseases such as cancer and COPD among others.
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