TY - JOUR
T1 - The use of peripheral μ-opioid receptor antagonists (PAMORA) in the management of opioid-induced constipation
T2 - An update on their efficacy and safety
AU - Pergolizzi, Joseph V.
AU - Christo, Paul J.
AU - Lequang, Jo Ann
AU - Magnusson, Peter
N1 - Funding Information:
JVP Jr is a consultant/speaker or researcher for Astra-Zeneca, US World Meds, BDSI, Salix, Enalare, Scilex, and Neumentum and is a principal at Native Cardio. He also reports personal fees from BDSI, during the conduct of the study; grants and/or personal fees from Salix and Astra Zeneca, outside the submitted work. PJC is on the advisory board of GlaxoSmithKline, Consumer Healthcare and is a consultant for Daichii Sankyo. He also reports personal fees from GlaxoSmithKline, Daiichi Sankyo, and BTG, assisted in media work for Algiatry, outside the submitted work. PM has received speaker fees or grants from Abbott, Alylam, Bayer, AstraZeneca, BMS, Boeringer-Ingelheim, Internetmedicine AB, Lilly, Novo Nordsik, Octupus Medical, Orion Pharma, Pfizer and Vifor Pharma. The authors report no other conflicts of interest in this work.
Publisher Copyright:
© 2020 Pergolizzi Jr et al. This work is published and licensed by Dove Medical Press Limited.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Constipation
KW - Methylnaltrexone
KW - Naldemedine
KW - Naloxegol
KW - Opioid antagonism
KW - Opioid-associated bowel disorder
KW - Opioid-associated side effects
KW - Pain
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U2 - 10.2147/DDDT.S221278
DO - 10.2147/DDDT.S221278
M3 - Review article
C2 - 32210534
AN - SCOPUS:85081545134
VL - 14
SP - 1009
EP - 1025
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
SN - 1177-8881
ER -