{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:52:37Z","timestamp":1763977957683,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T00:00:00Z","timestamp":1457222400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid\u2010induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu\u2010opioid receptors are specifically responsible for opioid\u2010induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid\u2010induced constipation or opioid\u2010induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid\u2010induced constipation. Axelopran (<jats:styled-content style=\"fixed-case\">TD<\/jats:styled-content>\u20101211) and sustained\u2010release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting \u03bc\u2010opioid receptor antagonists. Naloxone essentially functions as a peripherally acting \u03bc\u2010opioid receptor antagonist when administered orally in a sustained\u2010release formulation. Lubiprostone is a locally acting chloride channel (<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>\u20102) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are needed to further define their role in therapy.<\/jats:p>","DOI":"10.1002\/phar.1711","type":"journal-article","created":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T06:42:45Z","timestamp":1457246565000},"page":"287-299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Novel Oral Therapies for Opioid\u2010induced Bowel Dysfunction in Patients with Chronic Noncancer Pain"],"prefix":"10.1002","volume":"36","author":[{"given":"Renee M.","family":"Holder","sequence":"first","affiliation":[{"name":"Department of Medicine Section\u00a0of Palliative Care MedStar Washington Hospital Center Washington District of Columbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Rhee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Roseman University of Health Sciences Henderson Nevada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2008.05.005"},{"key":"e_1_2_5_3_1","unstructured":"Food Drug Administration Center for Drug Evaluation Research.Briefing Document: Anesthetic and Analgesic Drug Products Advisory Committee Meeting June 2014. 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