Methylnaltrexone for Reversal of Constipation Due to Chronic Methadone Use
01 Jan 2017-
TL;DR: It is demonstrated that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages and may have clinical utility in managing opioid-induced constipation.
About: The article was published on 2017-01-01 and is currently open access. It has received 260 citations till now. The article focuses on the topics: Methylnaltrexone & Methadone.
Citations
More filters
TL;DR: No data support any beneficial effect of ileus and indeed it may contribute to delayed recovery and prolonged hospital stay, so efforts should be made to reduce such ileu.
Abstract: Background
Postoperative ileus has traditionally been accepted as a normal response to tissue injury. No data support any beneficial effect of ileus and indeed it may contribute to delayed recovery and prolonged hospital stay. Efforts should, therefore, be made to reduce such ileus.
Methods
Material was identified from a Medline search of the literature, previous review articles and references cited in original papers. This paper updates knowledge on the pathophysiology and treatment of postoperative ileus.
Results and conclusion
Pathogenesis mainly involves inhibitory neural reflexes and inflammatory mediators released from the site of injury. The most effective method of reducing ileus is thoracic epidural blockade with local anaesthetic. Opioid-sparing analgesic techniques and non-steroidal anti-inflammatory agents also reduce ileus, as does laparoscopic surgery. Of the prokinetic agents only cisapride is proven beneficial; the effect of early enteral feeding remains unclear. However, postoperative ileus may be greatly reduced when all of the above are combined in a multimodal rehabilitation strategy. © 2000 British Journal of Surgery Society Ltd
575 citations
TL;DR: The data suggest that combination treatment with once-daily metformin-rosiglitazone improves glycemic control, insulin sensitivity, and beta-cell function more effectively than treatment with met formin alone.
Abstract: Context Most antidiabetic agents target only 1 of several underlying causes of diabetes. The complementary actions of the antidiabetic agents metformin hydrochloride and rosiglitazone maleate may maintain optimal glycemic control in patients with type 2 diabetes; therefore, their combined use may be indicated for patients whose diabetes is poorly controlled by metformin alone. Objective To evaluate the efficacy of metformin-rosiglitazone therapy in patients whose type 2 diabetes is inadequately controlled with metformin alone.
550 citations
TL;DR: Current management of opioid-induced bowel dysfunction among patients receiving opioid analgesics consists primarily of nonspecific ameliorative measures and 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.
Abstract: 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.
534 citations
TL;DR: 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.
Abstract: 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.
531 citations
Cites background from "Methylnaltrexone for Reversal of Co..."
...Clinically, ADL 8-2698 reduced morphine-induced delays in GI transit without affecting centrally mediated opioid effects such as analgesia and pupillary constriction [43,44,47,48]....
[...]
TL;DR: Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation and did not appear to affect central analgesia or precipitate opioid withdrawal.
Abstract: Background Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a μ-opioid–receptor antagonist, has restricted ability to cross the blood–brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. Methods A total of 133 patients who had received opioids for 2 or more weeks and who had received stable doses of opioids and laxatives for 3 or more days without relief of opioid-induced constipation were randomly assigned to receive subcutaneous methylnaltrexone (at a dose of 0.15 mg per kilogram of body weight) or placebo every other day for 2 weeks. Coprimary outcomes were laxation (defecation) within 4 hours after the first dose of the study drug and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial. Results In the methylnaltrexone group, 48% o...
495 citations
References
More filters
TL;DR: The American Cancer Society's Department of Epidemiology and Statistics reports its 29th annual compilation of cancer incidence, survival and mortality data for the United States and around the world.
Abstract: The American Cancer Society's Department of Epidemiology and Statistics reports its 29th annual compilation of cancer incidence, survival and mortality data for the United States and around the world.
1,441 citations
Journal Article•
TL;DR: Pulmonary H2 excretion was used to quantitate the small bowel transit time in man and appears to provide a simple, safe, and noninvasive means of studying small bowel Transit Time in man.
439 citations
Journal Article•
TL;DR: A short, "double-blind," direct addiction, cross-over procedure of 18 to 20 days is satisfactory for developing significant degrees of physical dependence in the case of morphine and codeine-like drugs, but additional studies are necessary to determine its reliability for assessing the degree ofPhysical dependence induced by weak compounds and compounds in the methadone and meperidine series.
Abstract: A method has been developed for quantifying the "attitude" of addicts toward opiate-like drugs when administered in single or chronic dosages. Questionnaires were used which provided for independently prepared ratings by patients and observers. In single doses, the effects of weak morphine-like drugs were readily differentiated from those of a placebo by both patients and aides. After single doses, the ratings of patients and observers were in good agreement; however, observers gave higher ratings than patients particularly in the parameters of "feel drug," identification as "dope," and degree of "liking." Although potent opiates given chronically by the subcutaneous route were classified by both patients and observers in a comparable manner, those given orally were divergently described. Both patients and observers readily differentiated a placebo from weak morphine-like drugs. Patients discriminated between drugs and route of administration to a greater extent than did observers, and in a manner which corresponded better with abuse rates for heroin, morphine and codeine. However, before a statement can be made about the relative validity of patients9 and observers9 ratings, many more drugs must be evaluated by diverse routes of administration and employing a larger sample of the addict population. A short, "double-blind," direct addiction, cross-over procedure of 18 to 20 days is satisfactory for developing significant degrees of physical dependence in the case of morphine and codeine-like drugs, but additional studies are necessary to determine its reliability for assessing the degree of physical dependence induced by weak compounds and compounds in the methadone and meperidine series.
260 citations
01 Jan 1977
TL;DR: In an attempt to develop analgesics, antitussives, and antidiarrheals that were devoid of those properties of morphine leading to abuse, a large number of drugs have been synthesized and studied.
Abstract: As therapeutic agents, morphine and morphinelike drugs are indispensable, but these same agents are liable to nontherapeutic self-ingestion by segments of the population. Society has condemned this self-ingestion and its associated behaviors and has invoked stringent legal mechanisms controlling the manufacture and distribution of morphinelike drugs. In an attempt to develop analgesics, antitussives, and antidiarrheals that were devoid of those properties of morphine leading to abuse, a large number of drugs have been synthesized and studied. Few drugs have been discovered which exhibit this selectivity, but many have been found that are pharmacologically equivalent to morphine with a potential similar to morphine for abuse.
257 citations
TL;DR: The current state of knowledge concerning the pharmacology of the quaternary narcotic antagonists is reviewed, their use in physiological and behavioral studies of action of opiates is examined, and guidelines for the design of experiments involving these compounds are proposed.
254 citations