benzofurans and Intestinal-Obstruction

Conservative treatment of fecal incontinence and obstructive defecation can be treated by many conservative treatment modalities. This article presents the options of medication therapy, spincter exercises, electric stimulation, transcutaneous tibial nerve stimulation, anal irrigation and injection of bulking agents. These methods are presented with reference to the currently available literature but the evidence-based data level for all methods is low. For minor disorders of anorectal function these conservative methods can lead to an improvement of anorectal function and should be individually adapted.

Topics: Anal Canal; Antidiarrheals; Benzofurans; Combined Modality Therapy; Electric Stimulation Therapy; Evidence-Based Medicine; Fecal Incontinence; Female; Humans; Intestinal Obstruction; Loperamide; Male; Pelvic Floor Disorders; Physical Therapy Modalities; Polyethylene Glycols; Randomized Controlled Trials as Topic; Serotonin 5-HT4 Receptor Agonists; Surface-Active Agents; Transcutaneous Electric Nerve Stimulation

Prucalopride is a selective serotonin receptor agonist with prokinetic activity, indicated for women with chronic constipation in whom laxatives have failed to provide adequate relief. Data suggests an improvement in about 50 % of such patients but whether the therapeutic effect is on patients with slow transit constipation (STC) and/or obstructed defaecation syndrome (ODS), or even those with constipation-predominant irritable bowel syndrome (IBS-C) is unknown. We therefore assessed whether there is any association between prucalopride efficacy and constipation type.. All patients receiving prucalopride between June 2010 and April 2012 at our institution were identified, and data analysed following a 4-week "test" period. Patients were sub-grouped as those suffering with ODS, STC, mixed (ODS and STC) or IBS-C based on symptomatology and investigations. Subjective assessment of patient satisfaction and continuation of medication were taken as positive outcomes and analysed for each sub-type along with any side effects.. Sixty-nine patients met our criteria. Data were available for 59 women (median age 46 years, range 17-79 years). Sixty-five per cent of prescriptions came from colorectal surgeons. Overall, 25 out of 59 (42 %) patients improved, according to our criteria, after the 4-week trial period. Seventeen patients (29 %) had ODS, 26 (44 %) had STC, 7 (12 %) had mixed symptoms and 9 (15 %) had IBS-C. At 4 weeks, 10 out of 17 patients (59 %) with ODS had improved compared with 4 out of 9 patients (44 %) with IBS-C, 3 out of 7 patients (43 %) with mixed symptoms and 8 out of 26 (31 %) patients with STC. The underlying disorder did not predict whether or not a patient responded to the 4-week trial period (p = 0.32). Nine patients (15 %) experienced side effects that precluded further use.. Patients with all categories of constipation may respond to prucalopride. A trial regime may be indicated regardless of the aetiology of the constipation.

Topics: Adolescent; Adult; Aged; Benzofurans; Cohort Studies; Constipation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gastrointestinal Transit; Humans; Intestinal Obstruction; Middle Aged; Patient Satisfaction; Retrospective Studies; Serotonin Receptor Agonists; Severity of Illness Index; Syndrome; Treatment Outcome; Young Adult

Topics: Benzofurans; Constipation; Female; Humans; Intestinal Obstruction; Serotonin Receptor Agonists

Intestinal disease in cystic fibrosis (CF) mice closely mirrors aspects of obstructive syndromes in CF patients. The pathogenesis involves accumulation of mucoid debris in the crypts that fuse with intestinal content to form obstructing mucofeculant impactions. Treatment involves modalities that increase the fluidity of the luminal content, such as osmotic laxatives and liquid diets. We investigated the effects of talniflumate (Lomucin, Genaera Corporation, Plymouth Meeting, PA), a compound that may be beneficial to treatment of CF intestinal disease based on three mechanisms of action: mucus synthesis inhibition by blockade of the murine calcium-activated chloride channel 3 (mCLCA3), nonsteroidal anti-inflammatory effects, and inhibition of Cl(-)/HCO (-)(3) exchanger(s) involved in intestinal NaCl absorption. Cohorts of CF mice were fed control diet or diets containing either talniflumate (0.4 mg/g chow) or ibuprofen (0.4 mg/g chow) for 21 days to assess survival. Talniflumate significantly increased CF mouse survival from 26 to 77%, whereas ibuprofen had no effect (22% survival). Oral talniflumate did not alter crypt goblet cell numbers or change intestinal expression of mCLCA3 but tended to decrease crypt mucoid impaction. Ussing chamber studies indicated that talniflumate slightly increased the basal short-circuit current of CF intestine, but the change was not sensitive to secretagogue stimulation or bumetanide inhibition. In contrast, intracellular pH measurements of intact intestinal villous epithelium indicated that talniflumate significantly inhibited apical membrane Cl(-)/HCO (-)(3) exchange by >50%. We conclude that oral talniflumate increases the survival of CF mice, possibly by the beneficial effects of decreasing small intestinal NaCl absorption through the inhibition of apical membrane Cl(-)/HCO (-)(3) exchanger(s).

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Cell Count; Chloride Channels; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Hydrogen-Ion Concentration; Intestinal Mucosa; Intestinal Obstruction; Intestine, Small; Ion Transport; Mice; Mucins; Mucoproteins; Mutation; Pyridines

Darifenacin (Enablex) and solifenacin (VESIcare) are 2 new oral anticholinergics available for once-daily symptomatic treatment of overactive bladder. Overactive bladder is a common condition in older patients. The 5 drugs currently approved for treatment are modestly effective but also cause anticholinergic adverse effects such as dry mouth and constipation and can cause confusion in the elderly. In some experimental studies, the new drugs particularly target bladder receptors, but the clinical significance of these findings is unknown.

Topics: Benzofurans; Drug Interactions; Humans; Intestinal Obstruction; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Urinary Incontinence; Xerostomia