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      Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey

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          Abstract

          Introduction

          Laxatives are commonly used to treat opioid-induced constipation, the commonest and most bothersome complication of opioids. However, laxatives have a nonspecific action and do not target underlying mechanisms of opioid-induced constipation; their use is associated with abdominal symptoms that negatively impact quality of life.

          Objective

          To assess the effects of laxatives in patients taking opioids for chronic pain.

          Methods

          One hundred ninety-eight UK patients who had taken opioid analgesics for at least one month completed a cross-sectional online or telephone survey. Questions addressed their pain condition, medication, and laxative use (including efficacy and side effects). The survey also assessed bowel function using the Bowel Function Index.

          Results

          Since starting their current opioid, 134 of 184 patients (73%) had used laxatives at some point and 122 (91%) of these were currently taking them. The most common laxatives were osmotics and stimulants. Laxative side effects were reported in 75%, most commonly gas, bloating/fullness, and a sudden urge to defecate. Side effects were more common in patients less than 40 years of age. Approximately half of patients said laxatives interfered with work and social activities, and one-fifth needed an overnight hospital stay because of their pain condition and/or constipation. Laxatives did not improve the symptoms of constipation, as assessed by the Bowel Function Index. Constipation was not related to opioid strength, dose of opioid, or number of laxatives taken.

          Conclusions

          Use of laxatives to treat opioid-induced constipation is often ineffective and associated with side effects. Instead of relieving the burden of opioid-induced constipation, laxative use is associated with a negative impact.

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          Most cited references22

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          Incidence, prevalence, and management of opioid bowel dysfunction.

          Opioid bowel dysfunction (OBD) is a common adverse effect associated with opioid therapy. OBD is commonly described as constipation; however, it is a constellation of adverse gastrointestinal (GI) effects, which also includes abdominal cramping, bloating, and gastroesophageal reflux. The mechanism for these effects is mediated primarily by stimulation of opioid receptors in the GI tract. In patients with pain, uncontrolled symptoms of OBD can add to their discomfort and may serve as a barrier to effective pain management, limiting therapy, or prompting discontinuation. Patients with cancer may have disease-related constipation, which is usually worsened by opioid therapy. However, OBD is not limited to cancer patients. A recent survey of patients taking opioid therapy for pain of noncancer origin found that approximately 40% of patients experienced constipation related to opioid therapy ( 50% of the time. Laxatives prescribed prophylactically and throughout opioid therapy may improve bowel movements in many patients. Nevertheless, a substantial number of patients will not obtain adequate relief of OBD because of its refractory nature. Naloxone and other tertiary opioid receptor antagonists effectively reduce the symptoms of constipation in opioid-treated patients. However, because they also act centrally, they may provoke opioid withdrawal symptoms or reverse analgesia in some patients. There are 2 peripherally selective opioid receptor antagonists, methylnaltrexone and ADL 8-2698 (Adolor Corporation, Exton, PA, USA), that are currently under investigation for their use in treating OBD. Early studies confirm that they are effective at normalizing bowel function in opioid-treated patients without entering the central nervous system and affecting analgesia. With a better understanding of the prevalence of OBD and its pathophysiology, a more aggressive approach to preventing and treating OBD is possible and will likely improve the quality of life of patients with pain.
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            Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden

            As a result of the undesired action of opioids on the gastrointestinal (GI) tract, patients receiving opioid medication for chronic pain often experience opioid-induced bowel dysfunction (OBD), the most common and debilitating symptom of which is constipation. Based on clinical experience and a comprehensive MEDLINE literature review, this paper provides the primary care physician with an overview of the prevalence, pathophysiology and burden of OBD. Patients with OBD suffer from a wide range of symptoms including constipation, decreased gastric emptying, abdominal cramping, spasm, bloating, delayed GI transit and the formation of hard dry stools. OBD can have a serious negative impact on quality of life (QoL) and the daily activities that patients feel able to perform. To relieve constipation associated with OBD, patients often use laxatives chronically (associated with risks) or alter/abandon their opioid medication, potentially sacrificing analgesia. Physicians should have greater appreciation of the prevalence, symptoms and burden of OBD. In light of the serious negative impact OBD can have on QoL, physicians should encourage dialogue with patients to facilitate optimal symptomatic management of the condition. There is a pressing need for new therapies that act upon the underlying mechanisms of OBD.
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              Opioid-induced bowel dysfunction: pathophysiology and potential new therapies.

              Opioid treatment for postoperative or chronic pain is frequently associated with adverse effects, the most common being dose-limiting and debilitating bowel dysfunction. Postoperative ileus, although attributable to surgical procedures, is often exacerbated by opioid use during and following surgery. Postoperative ileus is marked by increased inhibitory neural input, heightened inflammatory responses, decreased propulsive movements and increased fluid absorption in the gastrointestinal tract. The use of opioids for chronic pain is characterised by a constellation of symptoms including hard dry stools, straining, incomplete evacuation, bloating, abdominal distension and increased gastroesophageal reflux. The current management of opioid-induced bowel dysfunction among patients receiving opioid analgesics consists primarily of nonspecific ameliorative measures. Intensive investigations into the mode of action of opioids have characterised three opioid receptor classes -mu, delta and kappa- that mediate the myriad of peripheral and central actions of opioids. Activation of mu-opioid receptors in the gastrointestinal tract is responsible for inhibition of gut motility, whereas receptors in the central nervous system mediate the analgesic actions of opioids. Blocking peripheral opioid receptors in the gut is therefore a logical therapeutic target for managing opioid-induced bowel dysfunction. Available opioid antagonists such as naloxone are of limited use because they are readily absorbed, cross the blood-brain barrier, and act at central opioid receptors to reverse analgesia and elicit opioid withdrawal. Methylnaltrexone and alvimopan are recently developed opioid antagonists with activity that is restricted to peripheral receptors. Both have recently shown the ability to reverse opioid-induced bowel dysfunction without reversing analgesia or precipitating central nervous system withdrawal signs in non-surgical patients receiving opioids for chronic pain. In addition, recent clinical studies with alvimopan suggest that it may normalise bowel function without blocking opioid analgesia in abdominal laparotomy patients with opioid-related postoperative ileus.
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                Author and article information

                Journal
                Pain Med
                Pain Med
                painmedicine
                Pain Medicine: The Official Journal of the American Academy of Pain Medicine
                Oxford University Press
                1526-2375
                1526-4637
                October 2017
                08 October 2016
                08 October 2016
                : 18
                : 10
                : 1932-1940
                Affiliations
                [* ]Department of Gastroenterology, University College Hospital, London, UK
                []Chronic Pain Policy Coalition (CPPC) Policy Connect, CAN Mezzanine, 32-36 Loman Street, London
                []Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, UK
                [§ ]Mundipharma International Limited, Cambridge, UK
                Author notes
                [* ] Correspondence to: Sara Dickerson, MSc, Mundipharma International Limited, 194 Cambridge Science Park, Milton Road, Cambridge, CB4 0AB, UK. Tel: +44-0-1223-424211; Fax: +44-0-1223-426-626 E-mail: sara.dickerson@ 123456mundipharma.co.uk .

                Funding sources: Napp Pharmaceuticals Limited funded the study. Anton Emmanuel works at University College London, which receives a proportion of funding from the National Institute for Health Research Comprehensive Biomedical Research Centre funding scheme.

                Disclosures and conflicts of interest: Anton Emmanuel has served on advisory boards and received speaker fees from Almirall, Medtronic, Mundipharma International Limited, Napp Pharmaceuticals Limited, Norgine, and Shire. Martin Johnson has served on advisory boards and given lectures sponsored by GlaxoSmithKline, Grünenthal, Mundipharma International Limited, Napp Pharmaceuticals Limited, and Pfizer. Paula McSkimming has received travel expenses from Mundipharma International Limited. Sara Dickerson is an employee of Mundipharma International Limited. Napp Pharmaceuticals Limited (the sponsor of the study) is an independent associate of Mundipharma International Limited.

                Article
                pnw240
                10.1093/pm/pnw240
                5914325
                28339544
                9da2a203-6601-436e-8f49-d46dfd332b84
                © 2016 American Academy of Pain Medicine.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Page count
                Pages: 9
                Funding
                Funded by: National Institute for Health Research 10.13039/501100000272
                Categories
                OPIOIDS & SUBSTANCE USE DISORDERS SECTION
                Original Research Articles

                Anesthesiology & Pain management
                 opioid,opioid-induced constipation,laxatives,chronic pain,survey,bowel function index

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