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Postoperative ileus (POI) and constipation are common secondary effects of opioids and carry significant clinical and economic impacts. μ-Opioid receptors mediate opioid analgesia in the central nervous system (CNS) and gastrointestinal-related effects in the periphery. Peripherally acting μ-opioid receptor antagonists (PAMORAs) block the peripheral effects of opioids in the gastrointestinal tract, while maintaining opioid analgesia in the CNS. While most are not approved for POI or postoperative opioid-induced constipation (OIC), PAMORAs have a potential role in these settings via their selective effects on the μ-opioid receptor. This review will discuss recent clinical trials evaluating the safety and efficacy of PAMORAs, with a focus on alvimopan (Entereg ® ) and methylnaltrexone (Relistor ® ) in patients with POI or postoperative OIC. We will characterize potential factors that may have impacted the efficacy observed in phase 3 trials and discuss future directions for the management and treatment of POI.

Peripherally Acting μ-Opioid Receptor Antagonists in the Management of Postoperative Ileus: a Clinical Review