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Expert Opinion on Pharmacotherapy Jul 2018The extensive and alarming use of opioids for pain management in patients with chronic pain receiving palliative care is associated with non-tolerable gastrointestinal... (Review)
Review
The extensive and alarming use of opioids for pain management in patients with chronic pain receiving palliative care is associated with non-tolerable gastrointestinal (GI) adverse effects. Opioid-induced constipation (OIC) is the most common adverse effect impairing patient quality of life (QOL). In addition, OIC is one of the treatment limiting consequences of opioid analgesics. Management of OIC is becoming a challenge since traditional laxatives have limited efficiency. Peripherally acting mu-opioid receptor antagonists (PAMORA) have been developed for the treatment of OIC with methylnaltrexone bromide being the first approved to treat OIC in adults with advanced illness undergoing palliative care. Areas covered: The authors systematically review the clinical evidence for methylnaltrexone bromide including a review of the pharmacokinetic and pharmacodynamic data along with clinical effectiveness and cost-effectiveness. Though there is a need for further long-term clinical investigation, there is a large body of evidence for both its efficacy and safety in the treatment of OIC. Expert opinion: Methylnaltrexone has both subcutaneous injection and oral dosage forms available in the market. The lack of more evidence in specific populations such as pregnant women, pediatrics and elderly still remains. The global consumption of methylnaltrexone shows a projection of increased use since its approval worldwide in 2008.
Topics: Analgesics, Opioid; Chronic Pain; Clinical Trials as Topic; Constipation; Government Regulation; Half-Life; Humans; Naltrexone; Quality of Life; Quaternary Ammonium Compounds; Treatment Outcome
PubMed: 29979903
DOI: 10.1080/14656566.2018.1491549 -
Expert Opinion on Drug Metabolism &... Feb 2011Opioid-induced constipation is a major side effect of the use of opioid pain medications in a palliative care population. At present, the only approved treatment for... (Review)
Review
INTRODUCTION
Opioid-induced constipation is a major side effect of the use of opioid pain medications in a palliative care population. At present, the only approved treatment for opioid-induced constipation is methylnaltrexone bromide subcutaneous injection. Methylnaltrexone is a peripherally restricted opioid antagonist with μ-opioid receptor selectivity that can reduce opioid activity in peripheral organs such as the gastrointestinal tract while sparing the pain relief afforded by the pain medications.
AREAS COVERED
This article addresses the pharmacokinetics of parenterally administered methylnaltrexone, including the studies in humans that form the basis for our understanding, and information on the disposition, metabolism and elimination of the drug. From this review, the reader will gain an understanding of the body's handling of methylnaltrexone following intravenous or subcutaneous administration.
EXPERT OPINION
Studies conducted to date indicate that methylnaltrexone has high bioavailability after subcutaneous administration at therapeutic dose levels, a terminal half-life of ∼ 8 - 9 h, minimal metabolism, elimination involving renal and non-renal routes, and a limited potential for drug-drug interactions. Combined with high efficacy and good tolerability, the predictable pharmacokinetic behavior of methylnaltrexone facilitates its successful utilization in clinical practice for the treatment of opioid-induced constipation in patients with advanced medical illness.
Topics: Clinical Trials as Topic; Constipation; Humans; Injections, Intravenous; Injections, Subcutaneous; Naltrexone; Narcotic Antagonists; Palliative Care; Quaternary Ammonium Compounds
PubMed: 21222554
DOI: 10.1517/17425255.2011.549824 -
Reviews in Gastroenterological Disorders 2009Constipation is a common problem associated with opiates and opioid compounds used for the treatment of pain and other medical conditions, and can influence patient... (Review)
Review
Constipation is a common problem associated with opiates and opioid compounds used for the treatment of pain and other medical conditions, and can influence patient quality of life. Methylnaltrexone appears effective in the therapy of opioid-induced constipation and will be useful for patients failing to respond to traditional laxative regimens.
Topics: Analgesics, Opioid; Clinical Trials as Topic; Constipation; Dose-Response Relationship, Drug; Drug Interactions; Gastrointestinal Transit; Half-Life; Humans; Infusions, Intravenous; Infusions, Subcutaneous; Laxatives; Naltrexone; Narcotic Antagonists; Postoperative Complications; Quaternary Ammonium Compounds
PubMed: 19898269
DOI: No ID Found -
British Journal of Nursing (Mark Allen...Up to 40% of patients taking opioids develop constipation. Opioid-induced constipation (OIC) may limit the adequate dosing of opioids for pain relief and reduce quality... (Review)
Review
Up to 40% of patients taking opioids develop constipation. Opioid-induced constipation (OIC) may limit the adequate dosing of opioids for pain relief and reduce quality of life. Health professionals must therefore inquire about bowel function in patients receiving opioids. The management of OIC includes carefully re-evaluating the necessity, type and dose of opioids at each visit. Lifestyle modification and alteration of aggravating factors, the use of simple laxatives and, when essential, the addition of newer laxatives or opioid antagonists (naloxone, naloxegol or methylnaltrexone) can be used to treat OIC. This review discusses the recent literature regarding the management of OIC and provides a rational approach to assessing and managing constipation in individuals receiving opioids.
Topics: Analgesics, Opioid; Chronic Pain; Constipation; Disease Management; Enema; Fluid Therapy; Humans; Laxatives; Narcotic Antagonists
PubMed: 27231750
DOI: 10.12968/bjon.2016.25.10.S4 -
The Oncologist Jul 2009
Review
Topics: Humans; Laxatives; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds
PubMed: 19605844
DOI: 10.1634/theoncologist.2009-0049 -
Journal of the American Association For... May 2023Opioids are an integral component of pain management for nonhuman primates. These potent analgesics also adverse gastrointestinal (GI) effects that include constipation,...
Opioids are an integral component of pain management for nonhuman primates. These potent analgesics also adverse gastrointestinal (GI) effects that include constipation, bloating, and delayed gastric emptying. Methylnaltrexone bromide (MNTX) is a selective, peripherally acting μ- and κ-opioid receptor antagonist that can be used to mitigate the GI effects associated with opioid administration. Unlike naltrexone, a similar drug in this class, MNTX possesses an N-methyl-quaternary amine group that prevents it from crossing the blood brain barrier. This blockage allows inhibition of peripheral GI opioid receptors without affecting opioid-mediated analgesia in the central nervous system. We conducted a pharmacokinetic analysis of MNTX in serum and CSF of 6 healthy juvenile male rhesus macaques after subcutaneous administration of a 0.15-mg/kg dose. We hypothesized that the macaques would demonstrate a T of 0.5 h, similar to that of humans, and that no MNTX would be detected in the CSF. This treatment resulted in a peak serum concentration of 114 ± 44 ng/mL at 0.25 ± 0.00 h; peak CSF at concentrations were 0.34 ± 0.07 ng/mL at the T. These data show that subcutaneous administration of MNTX to rhesus macaques may block peripheral adverse effects of opioids without interfering with their central analgesic effects.
Topics: Humans; Male; Animals; Naltrexone; Macaca mulatta; Narcotic Antagonists; Analgesics, Opioid; Quaternary Ammonium Compounds
PubMed: 37080736
DOI: 10.30802/AALAS-JAALAS-22-000111 -
Nature Reviews. Gastroenterology &... May 2016Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute or transient constipation can be due to changes in diet, travel or stress, and secondary... (Review)
Review
Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute or transient constipation can be due to changes in diet, travel or stress, and secondary constipation can result from drug treatment, neurological or metabolic conditions or, rarely, colon cancer. A diagnosis of primary chronic constipation is made after exclusion of secondary causes of constipation and encompasses several overlapping subtypes. Slow-transit constipation is characterized by prolonged colonic transit in the absence of pelvic floor dysfunction. This subtype of constipation can be identified using either the radio-opaque marker test or wireless motility capsule test, and is best treated with laxatives such as polyethylene glycol or newer agents such as linaclotide or lubiprostone. If unsuccessful, subspecialist referral should be considered. Dyssynergic defecation results from impaired coordination of rectoanal and pelvic floor muscles, and causes difficulty with defecation. The condition can be identified using anorectal manometry and balloon expulsion tests and is best managed with biofeedback therapy. Opioid-induced constipation is an emerging entity, and several drugs including naloxegol, methylnaltrexone and lubiprostone are approved for its treatment. In this Review, we provide an overview of the burden and pathophysiology of chronic constipation, as well as a detailed discussion of the available diagnostic tools and treatment options.
Topics: Acute Disease; Adult; Algorithms; Biofeedback, Psychology; Cathartics; Chronic Disease; Colectomy; Constipation; Dietary Fiber; Digital Rectal Examination; Gastrointestinal Transit; Humans; Irritable Bowel Syndrome; Laxatives; Lumbosacral Plexus; Manometry; Medical Records; Nonprescription Drugs; Risk Factors; Serotonin Agents; Transcutaneous Electric Nerve Stimulation
PubMed: 27033126
DOI: 10.1038/nrgastro.2016.53 -
The American Journal of Hospice &... Feb 2011Opioids have become the gold standard for treatment of severe pain in advanced disease, but adverse effects can affect the quality of life. Opioid-induced bowel... (Review)
Review
Opioids have become the gold standard for treatment of severe pain in advanced disease, but adverse effects can affect the quality of life. Opioid-induced bowel dysfunction can lead to refractory constipation. Methylnaltrexone bromide is a peripherally acting mu antagonist and is indicated for the treatment of opioid-induced constipation in patients with advanced illness, when response to standard laxative therapy has been inefficacious. This pharmacology update will review the etiology, pathophysiology, and treatment of opioid-induced constipation, focused on methylnaltrexone as a novel treatment for refractory cases.
Topics: Analgesics, Opioid; Constipation; Defecation; Humans; Naltrexone; Narcotic Antagonists; Pain, Intractable; Palliative Care; Quality of Life; Quaternary Ammonium Compounds
PubMed: 20801917
DOI: 10.1177/1049909110373507 -
Drugs May 2010Methylnaltrexone is a selective mu-opioid receptor antagonist that has restricted ability to cross the blood-brain barrier, thus enabling reversal of opioid-induced... (Review)
Review
Methylnaltrexone is a selective mu-opioid receptor antagonist that has restricted ability to cross the blood-brain barrier, thus enabling reversal of opioid-induced peripheral effects, such as constipation, without affecting the central effects, such as pain relief. Treatment with subcutaneous methylnaltrexone 0.15-0.30 mg/kg, relative to placebo, significantly increased the rescue-free laxation response rate within 4 hours of the first dose (primary endpoint) in adult patients with opioid-induced constipation and advanced illness in two randomized, double-blind, placebo-controlled, multicentre, phase III studies; one was a single-dose study (n = 154), the other a multiple-dose study (n = 133). In the multiple-dose study, rescue-free laxation response rates within 4 hours after at least two of the first four doses (coprimary endpoint) were also significantly higher in methylnaltrexone recipients than in placebo recipients. Moreover, median time to laxation after the first dose was significantly shorter in methylnaltrexone recipients than in placebo recipients in both studies. Methylnaltrexone was not associated with any significant changes in pain scores or central opioid withdrawal in these studies. Methylnaltrexone was generally well tolerated in clinical trials; most adverse events were of mild to moderate severity.
Topics: Analgesics, Opioid; Constipation; Humans; Molecular Structure; Naltrexone; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Treatment Outcome
PubMed: 20426500
DOI: 10.2165/11204520-000000000-00000