A case of life-threatening loperamide toxicity

3 out of 5 stars Severe loperamide toxicity associated with the use of cimetidine to potentiate the “high.” Hughes A et al. AM J Emerg Med 2018 May 15 [Epub ahead of print] Reference The potential adverse effects of loperamide (Imodium) are often underestimated since, even though it is an opioid, it is available over-the-counter and has been since 1988. Loperamide is used to treat diarrhea. It acts on the mu-opioid receptors in the gut, decreasing gastric motility. It is rather effective at this. However at therapeutic doses (2-16 mg per day) it does not cause central opioid effects such as euphoria or relief from opioid withdrawal symptoms. There are several reasons for this. Oral loperamide has limited bioavailability, estimated at less than 1%. It undergoes significant first-pass metabolism  via the hepatic cytochrome P450 (CYP) system. In addition, much of the ingested dose of loperamide does not get absorbed systemically in the first place, since it is actively pumped back into the gut by P-glycoprotein (P-gp). The P-glycoprotein efflux pump is also active at the blood-brain barrier, ejecting harmful substances before they reach the central nervous system. In a recent column on the topic, I pictured P-gp as a physiological bouncer, a molecular Mr. T. However, massive amounts of loperamide can overwhelm these defense mechanisms and enter the CNS in significant amounts, achieving central levels sufficient to cause opioid effects and euphoria, and suppress w...
Source: The Poison Review - Category: Toxicology Authors: Tags: Medical imodium loperamide overdose toxicity Source Type: news