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1/ Toxicologists are familiar with loperamide toxicity, but this hasn’t spread as much to other specialities. Thus, my 1st attempt at #tweetorial for #medtwitter . H/T to @jmmarraffa & @DavidJuurlink & @Pete_Wu for their earlier writings. Thxs to @officialdrk12 for the idea
2/ First a poll: Loperamide is/can be:
3/ Loperamide is a mu-opioid agonist with poor oral bioavailability with primary use as an anti-diarrheal. CNS effects are limited when p-glycoprotein (P-GP) is functioning normally at the blood-brain barrier.
4/ In massive (>50-100x usual dose) loperamide ingestions, however, P-GP becomes overwhelmed and >amts become bioavailable, leading to expected opioid CNS effects. Why would people do this? nj1015.com/people-in-nj-a…
5/ Early 1980s reports felt that loperamide had low abuse potential (PMID: 7438696) but more recently it has been described in large doses as “Poor Man’s Methadone” (PMID: 28506439) to avoid opioid withdrawal, or to achieve a psychoactive effect.
6/ Loperamide is a CYP3A4 and P-GP substrate. To potentiate loperamide’s effects, pts may co-ingest grapefruit juice or cimetidine to inhibit CYP3A4; or black pepper to inhibit P-GP. (Finally, grapefruit juice intake is relevant.) 
7/ In early 2010s (@jmmarraffa PMID: 25345436) reports arose among toxicologists of severe cardiac toxicity following massive loperamide ingestions. @DavidJuurlink previously posted these scary ECGs.
8/ At supratherapeutic concentrations, loperamide inhibits cardiac fast Na channels and HERG K channels, resulting in wide QRS and prolonged QTc which can progress to malignant ventricular dysrhythmias. Pts may present with recurrent syncope or cardiac arrest.
9/ For CNS and respiratory depression, naloxone can be used for reversal. For widened QRS, boluses of NaHCO3 1-2mEq/kg over 1-2 min may help. A bicarb drip may be counterproductive by extending the QTc. See @thecurbsiders w/ @dantastictox below.
10/ Most concerning may be the incredibly prolonged QTc (frequently noted as >680msec) 😮. It’s reasonable to normalize all cations (K, Ca, Mg), and get prepared for arrhythmias/torsades. Tachycardia protects against torsades, so consider overdrive pacing via drugs/electricity.
11/ Hard to say how long these effects may last, maybe several days. The natural effect of loperamide would be to delay its own gut absorption, plus there may be co-ingestants intended to decrease metabolism as above.
12/ Another poll to review: Loperamide in large doses is/can
13/ Additional reading @ PMID: 28506439, excellent review of loperamide toxicity @ToxAndHound @ emcrit.org/toxhound/worst…
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@ogi_gajic @medpedshosp @KCToxikin
Thanks for following//END//
@ogi_gajic @medpedshosp @KCToxikin
