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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 -
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 -
Journal of the Advanced Practitioner in... 2019Opioid-induced constipation (OIC) is a common adverse effect associated with opioid therapy, with many patients never developing tolerance to this effect. There are many... (Review)
Review
Opioid-induced constipation (OIC) is a common adverse effect associated with opioid therapy, with many patients never developing tolerance to this effect. There are many traditional laxatives available to help patients combat this symptom, yet OIC may not reliably respond to conventional treatment. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have a place in the treatment of refractory OIC, when traditional laxatives have not resulted in effective laxation. There are a number of PAMORAs now available, and methylnaltrexone is the only PAMORA indicated for the treatment of OIC in adults with advanced illness, as well as for patients with chronic noncancer pain, including patients with chronic pain related to prior cancer treatment who do not require frequent opioid escalation. Advanced practitioners need to have an understanding of how and when to best use these medications for the different indications in patients with advanced illness or chronic noncancer-related pain.
PubMed: 31308989
DOI: No ID Found -
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 -
The Medical Letter on Drugs and... Apr 2018
Topics: Abuse-Deterrent Formulations; Acute Pain; Administration, Oral; Analgesics, Opioid; Chronic Pain; Drug Interactions; Drug Tolerance; Humans; Opioid-Related Disorders; Treatment Outcome
PubMed: 29664446
DOI: No ID Found -
Postgraduate Medicine 2016Constipation is a common adverse effect in patients requiring long-term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Constipation is a common adverse effect in patients requiring long-term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor antagonist, is an effective treatment of opioid induced constipation (OIC) without affecting centrally mediated analgesia. Our objective was to conduct a review and meta-analysis to evaluate the efficacy of methylnaltrexone for treatment of OIC, as well as to provide a clinical discussion regarding newly developed alternatives and provide the current treatment algorithm utilized at our institution.
METHODS
We performed a systematic review and meta-analysis of randomized control trials using Cochrane Collaboration Databases and MEDLINE from 2007-present. Literature related to methylnaltrexone, opioids, opioid receptors, opioid antagonists, opioid-induced constipation were reviewed. A meta-analysis was completed with the primary outcome of rescue-free bowel movement (RFBM) within four hours of administration. All pooled analyses were based on random-effects models.
RESULTS
1239 patients were analyzed; 599 received methylnaltrexone and 640 received placebo. With a 95% CI calculated, the true risk difference is between 0.267 and 0.385, demonstrating a statistically significant difference in RFBM between treatment and placebo groups (p < 0.0001). Both the 0.15 mg/kg, 0.30 mg/kg doses every other day, and 12 mg/day dose were found to have increased risk of RFBM compared to placebo.
CONCLUSION
Results support the use of methylnaltrexone. Furthermore, the use of methylnaltrexone to induce laxation may decrease use of health care resources, increase work productivity, and improve cost utilization. New treatments have been made available; however, controlled clinical studies are needed to demonstrate long-term efficacy, safety and cost-effectiveness. Possible limitations of this study include the relatively small number of randomized, placebo-controlled trials investigating the efficacy of methylnaltrexone versus placebo. There is also the possibility of publication bias, which may lead to overestimating the efficacy of methylnaltrexone in treating OIC.
Topics: Analgesics, Opioid; Chronic Pain; Constipation; Humans; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Treatment Outcome
PubMed: 26839023
DOI: 10.1080/00325481.2016.1149017 -
BMJ Clinical Evidence Sep 2015Constipation is a common adverse effect of opioids. As an example, constipation is reported in 52% of people with advanced malignancy, and this figure rises to 87% in... (Review)
Review
INTRODUCTION
Constipation is a common adverse effect of opioids. As an example, constipation is reported in 52% of people with advanced malignancy, and this figure rises to 87% in people who are terminally ill and taking opioids. There is no reason to believe that people with chronic non-malignant disease who are prescribed opioids will be any less troubled by this adverse effect.
METHODS AND OUTCOMES
We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of opioid antagonists for constipation in people prescribed opioids? The population we studied included people with any condition, although most studies were in people with cancer pain. We searched Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review).
RESULTS
At this update, searching of electronic databases retrieved 162 studies. After deduplication and removal of conference abstracts, 84 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 47 studies and the further review of 37 full publications. Of the 37 full articles evaluated, two systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for three PICO combinations.
CONCLUSIONS
In this systematic overview we categorised the efficacy for three interventions based on information relating to the effectiveness of alvimopan, methylnaltrexone, and naloxone.
Topics: Analgesics, Opioid; Constipation; Gastrointestinal Agents; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Piperidines; Quaternary Ammonium Compounds; Treatment Outcome
PubMed: 26360669
DOI: No ID Found -
Current Oncology Reports Oct 2022Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on... (Review)
Review
PURPOSE OF REVIEW
Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action.
RECENT FINDINGS
We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.
Topics: Cell Proliferation; Humans; Naltrexone; Narcotic Antagonists; Neoplasms; Quaternary Ammonium Compounds; Receptors, Opioid
PubMed: 35648340
DOI: 10.1007/s11912-022-01295-z -
The American Journal of Medicine Apr 2015
Topics: Abdominal Pain; Adult; Analgesics, Opioid; Anorexia; Chronic Disease; Diabetes Mellitus, Type 1; Drug Administration Schedule; Endoscopy, Gastrointestinal; Gastroparesis; Humans; Hypertension; Kidney Failure, Chronic; Male; Naltrexone; Narcotic Antagonists; Nausea; Neuralgia; Quaternary Ammonium Compounds; Substance Withdrawal Syndrome; Treatment Outcome; Vomiting
PubMed: 25460532
DOI: 10.1016/j.amjmed.2014.10.044 -
The Journal of Pediatric Pharmacology... 2022To evaluate the association between methylnaltrexone and urine output (UOP) in critically ill children with opioid-associated urinary retention.
OBJECTIVE
To evaluate the association between methylnaltrexone and urine output (UOP) in critically ill children with opioid-associated urinary retention.
METHODS
This retrospective study included patients admitted to the pediatric intensive care unit between December 1, 2019, and November 30, 2020, who received methylnaltrexone for opioid-associated oliguria (spontaneous UOP below 1 mL/kg/hr and at least 1 dose of an opioid within the preceding 6 hours).
RESULTS
Twenty-five patients (median age = 5.5 years, IQR 1.7-16.4; median weight = 19 kg, IQR 9-45) were included. Mean methylnaltrexone dose was 0.15 ± 0.006 mg/kg. A statistically significant increase in UOP from baseline to 6 hours following methylnaltrexone was observed (p = 0.001), but not all patients responded. Fourteen patients (56%) had no UOP following methylnaltrexone administration, while 11 (44%) demonstrated a robust increase (median = 0 mL/kg/hr at baseline [IQR 0-0] to 1.96 mL/kg/hr [IQR 1.08-2.22; p = 0.001]) within 6 hours following methylnaltrexone administration. Younger patients responded better than older patients (responder age = 2.5 years [IQR 0.8-7]) versus 11.4 years [IQR 1.75-17.5] for non-responders) (p = 0.04). Both intravenous (IV) and subcutaneous (SQ) routes were associated with an increase in UOP (IV, p = 0.04; SQ, p = 0.02). The effect persisted for up to 24 hours after administration. Sixty-four percent of patients required urinary catheter placement. Pain scores (averaged 6 hours before and after methylnaltrexone) remained unchanged (p = 0.44).
CONCLUSIONS
Methylnaltrexone may increase spontaneous UOP in some children with opioid-associated urinary retention, but urinary catheterization rates remain high.
PubMed: 35558358
DOI: 10.5863/1551-6776-27.4.373