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Cureus Apr 2021The present study discusses opioid-induced constipation (OIC) in advanced cancer patients, focusing on the OIC definition, pathophysiology, and treatment. OIC is any... (Review)
Review
The present study discusses opioid-induced constipation (OIC) in advanced cancer patients, focusing on the OIC definition, pathophysiology, and treatment. OIC is any change from baseline defecation patterns and bowel habits that developed after starting opioid therapy. The condition is characterized by bowel frequency reduction, worsening or development of straining, a sensation of incomplete defecation, or distress associated with bowel habits. OIC is common in advanced cancer patients, with a prevalence of approximately 51%-87% in patients taking opioids for pain management. Patients are likely to experience severe distress, work productivity reduction, poor quality of life, and increased healthcare utilization. OIC has a complex pathophysiology that involves propulsive and peristalsis impairment, intestinal mucosal secretion inhibition, intestinal fluid absorption enhancement, and anal sphincters function impairment. The Rome III criteria are used to assess and diagnose clinical OIC and can also be diagnosed through the Patient Assessment of Constipation (PAC) measures, including the symptom survey (PAC-SYM) and quality of life survey (PAC-QOL). Non-pharmacological treatment of OIC involves lifestyle habits and dietary adjustments, although these interventions might be insufficient to manage the condition. Pharmacological treatments involve the use of traditional laxatives and newer agents like peripherally acting mu-opioid receptor agonists (PAMORAs), including naldemedine, naloxegol, and methylnaltrexone. More novel treatments for OIC that target the pathophysiology are still needed and should be studied carefully for safety and efficacy.
PubMed: 33850679
DOI: 10.7759/cureus.14386 -
Scientific Reports Jul 2019Opioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use and can significantly impact quality of life, especially in...
Opioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use and can significantly impact quality of life, especially in patients with advanced illness. Methylnaltrexone has proven effective in treating cancer patients with OIC who have not responded adequately to conventional laxative therapy, though use is relatively contraindicated in those with peritoneal carcinomatosis due to theoretical risk and reported cases of perforation. The aim of this study was to evaluate the safety of methylnaltrexone in patients with carcinomatosis. We performed a retrospective review of 3058 pediatric and adult patients who received methylnaltrexone at Memorial Sloan Kettering Cancer Center from 2009-2016. Data collected included age, cancer diagnosis, history of abdominal surgery, prior radiation therapy, evidence of peritoneal carcinomatosis, and complications. Charts were reviewed for any complications at 24 hours, 72 hours, and one week following drug administration, as well as at present. We identified 3058 patients (median age 56, range 1-95) who received a total of 3995 doses of methylnaltrexone. Three hundred thirty three (median age 55, range 4-88) had peritoneal carcinomatosis. The most common primary malignancies included pancreatic (17.7%), ovarian (13.5%), colon (7.2%), and lung (6.6%). 228/333 (68.4%) had a history of abdominal surgery and 85/333 (25.5%) underwent prior radiation therapy. Three patients had adverse outcomes or complications, with only one (0.3%) thought to be related to methylnaltrexone use. To our knowledge, this is the largest study to evaluate the outcomes of patients with carcinomatosis receiving methylnaltrexone and the first to include pediatric patients. We found one perforation attributed to methylnaltrexone. Methylnaltrexone should be considered for treatment of refractory OIC in cancer patients with peritoneal carcinomatosis due to low risk of complications.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Child; Child, Preschool; Constipation; Female; Humans; Infant; Male; Middle Aged; Naltrexone; Peritoneal Neoplasms; Quaternary Ammonium Compounds; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 31270339
DOI: 10.1038/s41598-019-44864-2 -
Clinical Drug Investigation May 2012Opioids are one of the most widely used therapies for the palliative treatment of cancer pain; however, despite their proven analgesic efficacy, they are associated with... (Review)
Review
Opioids are one of the most widely used therapies for the palliative treatment of cancer pain; however, despite their proven analgesic efficacy, they are associated with several adverse effects. Associated with psychological distress and multiple concomitant clinical concerns, constipation is the most commonly occurring adverse effect of chronic opioid therapy in cancer patients. Whilst prophylaxis remains the first-line management option, methylnaltrexone is a recommended treatment option for opioid-related constipation if administration of laxatives is ineffective. Due to its inability to cross the blood-brain barrier, methylnaltrexone exerts a peripheral inhibition of opioid-related effects without influencing the opioid-induced central effects; as a result, the analgesic effect of opioids is unaffected. Moreover, multiple clinical trials, albeit not always conducted specifically in cancer patients, have demonstrated that up to 4 months' treatment with either intravenous or subcutaneous methylnaltrexone provides effective relief from opioid-related constipation and is well tolerated. Preliminary evidence indicates that the addition of methylnaltrexone to standard care for opioid-related constipation may also be advantageous from a pharmacoeconomic perspective. In addition, preliminary data suggest that methylnaltrexone could be associated with some further clinical benefits other than the treatment of opioid-related constipation, such as the improvement of gastric emptying, the relief of nausea/vomiting, and the reduction of the risk of regurgitation and pulmonary aspiration. This narrative review examines the most recent evidence and evaluates the current role of methylnaltrexone in the management of opioid-related constipation, and its potential efficacy in cancer patients. The pharmacokinetics, pharmacodynamics, efficacy and tolerability of methylnaltrexone are discussed.
Topics: Analgesics, Opioid; Constipation; Humans; Naltrexone; Narcotic Antagonists; Neoplasms; Pain; Palliative Care; Quaternary Ammonium Compounds
PubMed: 22413747
DOI: 10.2165/11598000-000000000-00000 -
Therapeutic Advances in Chronic Disease Mar 2016Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with... (Review)
Review
Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain.
PubMed: 26977281
DOI: 10.1177/2040622315627801 -
Current Oncology Reports Dec 2015Constipation is common in the general population and for those on opioids and/or who are suffering from advanced cancer. Self-management consists of dietary changes,... (Review)
Review
Constipation is common in the general population and for those on opioids and/or who are suffering from advanced cancer. Self-management consists of dietary changes, exercise, and laxatives. However, responses to self-management efforts are often inadequate to relieve the subjective and objective experience of constipation. Multiple new anti-constipating medications have recently been tested in randomized trials and the following are available commercially: probiotics, prucalopride, lubiprostone, linaclotide, elobixibat, antidepressants, methylnaltrexone, alvimopan, and naloxegol. This review will discuss the evidence-based benefits of these medications and outline an approach to managing constipation.
Topics: Analgesics, Opioid; Carrier Proteins; Chloride Channel Agonists; Constipation; Gastrointestinal Agents; Humans; Laxatives; Membrane Glycoproteins; Neoplasms; Probiotics; Randomized Controlled Trials as Topic
PubMed: 26449843
DOI: 10.1007/s11912-015-0481-x -
Drugs Aug 2013Most prescribed opioids exert their analgesic effects via activation of central μ-opioid receptors. However, μ-opioid receptors are also located in the... (Review)
Review
Most prescribed opioids exert their analgesic effects via activation of central μ-opioid receptors. However, μ-opioid receptors are also located in the gastrointestinal (GI) tract, and activation of these receptors by opioids can lead to GI-related adverse effects, in particular opioid-induced constipation (OIC). OIC has been associated with increased use of healthcare resources, increased healthcare costs, and decreased quality of life for patients. Nonpharmacologic (e.g., increased fiber uptake) and pharmacologic agents (e.g., laxatives) may be considered for the treatment and prevention of OIC. However, many interventions, such as laxatives alone, are generally insufficient to reverse OIC because they do not target the underlying cause of OIC, opioid activation of μ-opioid receptors in the GI tract. Therefore, there has been keen interest in antagonism of the μ-opioid receptor in the periphery to inhibit the effects of opioids in the GI tract. In this review, currently available pharmacologic therapies for the treatment and prevention of OIC are summarized briefly, with a primary focus on the administration of the peripheral μ-opioid receptor antagonist methylnaltrexone bromide in patients with OIC and advanced illness who are receiving palliative care. Also, clinical trial data of methylnaltrexone treatment in patients with OIC and other pain conditions (i.e., chronic noncancer pain and pain after orthopedic surgery) are reviewed. Data support that methylnaltrexone is efficacious for the treatment of OIC and has a favorable tolerability profile.
Topics: Analgesics, Opioid; Clinical Trials as Topic; Constipation; Dietary Fiber; Humans; Laxatives; Naltrexone; Narcotic Antagonists; Pain; Quaternary Ammonium Compounds; Receptors, Opioid, mu
PubMed: 23881667
DOI: 10.1007/s40265-013-0084-5 -
Current Opinion in Investigational... Jan 2008Progenics Pharmaceuticals Inc and Wyeth Pharmaceuticals are developing methylnaltrexone, a micro-receptor opioid antagonist derived from naltrexone by the addition of a... (Review)
Review
Progenics Pharmaceuticals Inc and Wyeth Pharmaceuticals are developing methylnaltrexone, a micro-receptor opioid antagonist derived from naltrexone by the addition of a methyl group. The intravenous formulation of methylnaltrexone is currently in phase III clinical trials for the potential treatment of postoperative ileus.
Topics: Analgesics, Opioid; Gastrointestinal Motility; Humans; Ileus; Naltrexone; Postoperative Complications; Postoperative Nausea and Vomiting; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Urinary Retention
PubMed: 18183536
DOI: No ID Found -
Journal of Pain and Symptom Management Jan 2008Opioid-induced bowel dysfunction is a distressing condition that may persist indefinitely in the clinical setting. As we understand more about normal gastrointestinal... (Review)
Review
Opioid-induced bowel dysfunction is a distressing condition that may persist indefinitely in the clinical setting. As we understand more about normal gastrointestinal (GI) physiology, we are also beginning to understand more fully how opioids cause bowel dysfunction. Current therapeutic interventions for opioid-induced bowel dysfunction can be burdensome and sometimes lack efficacy. Systemic opioid antagonists administered orally can induce laxation, but can unpredictably induce systemic or local GI tract withdrawal symptoms. Two new investigational agents, alvimopan and methylnaltrexone, are peripherally acting opioid antagonists that do not cross the blood-brain barrier. Studies to date show promise that these agents may relieve opioid-induced bowel dysfunction in a well-tolerated manner without reversing central analgesia.
Topics: Analgesics, Opioid; Animals; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Narcotic Antagonists
PubMed: 17981003
DOI: 10.1016/j.jpainsymman.2007.01.017 -
Journal of Visceral Surgery Mar 2022Postoperative constipation occurs relatively frequently, and can involve drug-related, surgical and lifestyle and dietary factors. Gastrointestinal motility can be...
Postoperative constipation occurs relatively frequently, and can involve drug-related, surgical and lifestyle and dietary factors. Gastrointestinal motility can be altered by inflammation, surgery, opioid medications, hypnotics, anti-secretory or anesthetic drugs or by functional modifications for which the physiopathology is not well defined. There are a number of laxatives available. These include bulk laxatives, osmotic laxatives and locally acting laxatives such as suppositories and enemas. Stimulant laxatives have a role to play in the short-term management of persistent constipation. 5-HT4 receptor antagonists are recommended in refractory constipation. Other specific therapeutic laxatives can be proposed such as methylnaltrexone in opioid-induced constipation or neostigmine in Ogilvie's syndrome. The prevention and/or early detection of iatrogenic constipation, whether postoperative or not, is essential and the knowledge how to improve patient comfort and reduce the duration of gastrointestinal motor disorders with specific drugs or other means is essential, particularly the postoperative period.
Topics: Analgesics, Opioid; Constipation; Digestive System Surgical Procedures; Humans; Iatrogenic Disease; Laxatives
PubMed: 35172956
DOI: 10.1016/j.jviscsurg.2021.12.003 -
Current Oncology Reports Jul 2007Cancer-related constipation is common and a significant detractor from patient quality of life. It has many possible causes and is still not well understood. Information... (Review)
Review
Cancer-related constipation is common and a significant detractor from patient quality of life. It has many possible causes and is still not well understood. Information is lacking on therapies for cancer-related constipation among current medications approved by the US Food and Drug Administration (FDA). Most agents have only been formally tested in comparison with placebo in chronic idiopathic constipation if at all. Few comparative studies of laxatives have been performed to establish superiority or synergy. As we understand more about the physiology of the gastrointestinal tract, new targeted therapies have become available. These include a selective chloride channel activator, lubiprostone, and a selective 5HT4 serotonin receptor agonist, tegaserod, both of which have been FDA approved for chronic idiopathic constipation. The role of these agents in cancer-related constipation remains to be seen. On the horizon are two investigational peripherally acting opioid receptor antagonists, alvimopan and methylnaltrexone. Preliminary results in cancer-related constipation suggest that these agents may be important additions to our treatment repertoire.
Topics: Alprostadil; Constipation; Fatty Acids; Gastrointestinal Agents; Humans; Indoles; Lubiprostone; Naltrexone; Narcotic Antagonists; Neoplasms; Piperidines; Quaternary Ammonium Compounds; Serotonin Receptor Agonists
PubMed: 17588352
DOI: 10.1007/s11912-007-0034-z