alvimopan-anhydrous and prucalopride

Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder.. This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition.

Topics: Anesthesia, Epidural; Animals; Benzofurans; Chewing Gum; Cholinergic Agents; Contrast Media; Cyclooxygenase Inhibitors; Diatrizoate Meglumine; Digestive System Surgical Procedures; Enhanced Recovery After Surgery; Enteral Nutrition; Enteric Nervous System; Fluid Therapy; Gastrointestinal Agents; Gastrointestinal Motility; Ghrelin; Humans; Ileus; Inflammation; Intestinal Pseudo-Obstruction; Intubation, Gastrointestinal; Laparoscopy; Mast Cells; Piperidines; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists; Sympathetic Nervous System; Sympatholytics

There has been no definitive synthesis of the evidence for any benefit of available pharmacological therapies in opioid-induced constipation (OIC). We conducted a systematic review and meta-analysis to address this deficit.. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials through to December 2012 to identify placebo-controlled trials of μ-opioid receptor antagonists, prucalopride, lubiprostone, and linaclotide in the treatment of adults with OIC. No minimum duration of therapy was required. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Effect of pharmacological therapies was reported as relative risk (RR) of failure to respond to therapy, with 95% confidence intervals (CIs).. Fourteen eligible randomized controlled trials (RCTs) of μ-opioid receptor antagonists, containing 4,101 patients, were identified. These were superior to placebo for the treatment of OIC (RR of failure to respond to therapy=0.69; 95% CI 0.63-0.75). Methylnaltrexone (six RCTs, 1,610 patients, RR=0.66; 95% CI 0.54-0.84), naloxone (four trials, 798 patients, RR=0.64; 95% CI 0.56-0.72), and alvimopan (four RCTs, 1,693 patients, RR=0.71; 95% CI 0.65-0.78) were all superior to placebo. Total numbers of adverse events, diarrhea, and abdominal pain were significantly commoner when data from all RCTs were pooled. Reversal of analgesia did not occur more frequently with active therapy. Only one trial of prucalopride was identified, with a nonsignificant trend toward higher responder rates with active therapy. Two RCTs of lubiprostone were found, with significantly higher responder rates with lubiprostone in both, but reporting of data precluded meta-analysis.. μ-Opioid receptor antagonists are safe and effective for the treatment of OIC. More data are required before the role of prucalopride or lubiprostone in the treatment of OIC are clear.

Topics: Alprostadil; Analgesics, Opioid; Benzofurans; Constipation; Female; Gastrointestinal Agents; Humans; Lubiprostone; Male; Naloxone; Naltrexone; Narcotic Antagonists; Peptides; Piperidines; Quaternary Ammonium Compounds; Receptors, Opioid, mu