Opioid-Induced Constipation: Challenges and Therapeutic Opportunities


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Abstract

There has been an alarming increase in the prescription of opiates and opioids for chronic non-cancer pain in the past 15 years. It is estimated that opiate-induced constipation (OIC) is experienced by ∼40% of these patients, and that constipation and other gastrointestinal symptoms may dissuade patients from using the required analgesic dose to achieve effective pain relief. Opiates have several effects on gastrointestinal functions, and the inhibition of colonic transit and intestinal and colonic secretion results in constipation. Several different pharmacological approaches are being developed to prevent or treat OIC: prolonged release formulations that contain naloxone (a less specific opiate antagonist that is widely distributed) and a new class of peripherally restricted μ-opiate receptor antagonists, including methylnaltrexone, alvimopan, tapentadol, NKTR-118, and TD-1211. Novel patient response outcomes have been developed to facilitate demonstration of efficacy and safety of drugs in development for OIC.

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