The use of peripheral μ-opioid receptor antagonists (PAMORA) in the management of opioid-induced constipation: An update on their efficacy and safety

Joseph V. Pergolizzi, Paul J. Christo, Jo Ann Lequang, Peter Magnusson

Research output: Contribution to journalReview articlepeer-review

Abstract

Peripherally acting μ-opioid receptor antagonists (PAMORAs) constitute a class of drugs which reverse opioid-induced constipation (OIC) with similar opioid analgesic effects. OIC differs from other forms of constipation in that it is an iatrogenic condition that occurs when an opioid acts on the dense network of μ-opioid receptors in the enteric system, which affect a variety of functions including gastrointestinal motility, secretion, and other factors that can cause bowel dysfunction. Unfortunately, laxative products, bowel regimens, dietary changes, and lifestyle modifications have limited effectiveness in preventing OIC, Opioid-associated adverse effect which occurs in 40% to 80% of opioid patients and may led to cessation of the treatment. PAMORAs are μ-receptor opioid antagonists specifically developed so that they have very limited ability to cross the blood-brain barrier and thus they are able to antagonize peripheral but not central μ-opioid receptors. PAMORAs are designed to have no effect on the analgesic benefits of opioid pain relievers but to relieve but antagonizing the effects of the opioid in the gastrointestinal system. The three main PAMORAS are methyl-trexone (oral or parenteral), naldemedine (oral only), and naloxegol (oral only). Clinical studies demonstrate the safety and efficacy of these agents for alleviating constipation without diminishing the analgesic effect of opioid therapy. The aim of this narrative review to update the current status of PAMORAs for treating OIC in terms of safety and efficacy.

Original languageEnglish (US)
Pages (from-to)1009-1025
Number of pages17
JournalDrug Design, Development and Therapy
Volume14
DOIs
StatePublished - 2020

Keywords

  • Constipation
  • Methylnaltrexone
  • Naldemedine
  • Naloxegol
  • Opioid antagonism
  • Opioid-associated bowel disorder
  • Opioid-associated side effects
  • Pain

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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