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Manabe N, Umeyama M, Ishizaki S, Ota T, Kuratani S, Katsumata R, Fujita M, Haruma K, Camilleri M. Elobixibat improves rectal sensation in patients with chronic constipation aged ≥60 years: a randomised placebo-controlled study. BMJ Open Gastroenterol 2023; 10:e001257. [PMID: 37993269 PMCID: PMC10668193 DOI: 10.1136/bmjgast-2023-001257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Accepted: 11/09/2023] [Indexed: 11/24/2023] Open
Abstract
OBJECTIVE High rectal sensory thresholds (RSTs) are associated with chronic constipation (CC), especially in older patients. Bile acids (BAs) affect the RSTs of healthy individuals. Here, we aimed to investigate the effects of the BA transporter inhibitor elobixibat in patients with CC aged ≥60 years. DESIGN We prospectively compared the RSTs of 17 patients with CC aged ≥60 years with those of 9 healthy individuals of the same age range. We next performed a prospective, randomised, parallel-group, double-blind, placebo-controlled clinical trial of 17 patients with CC who administered elobixibat or placebo daily for 1 week. Using barostat methodology, their first constant sensation volume (FCSV), defaecatory desire volume (DDV), and maximum tolerable volume (MTV) thresholds; their rectal compliance; and their faecal BA concentrations were measured before and after treatment. RESULTS There were no significant differences in the RSTs of healthy individuals and patients with CC, but all of these tended to be higher in the latter group. Elobixibat increased the desire to defaecate, significantly reduced the threshold for FCSV (p=0.0018), and tended to reduce the threshold for DDV (p=0.0899) versus placebo. However, there were no differences in the MTV or rectal compliance of the two groups. The total faecal BA concentration increased, and particularly that of secondary BAs in the elobixibat group. Elobixibat was most efficacious in participants with a longer duration of CC and a history of treatment for CC. CONCLUSION Elobixibat reduces the RSTs of patients with CC aged ≥60 years, which may be important for its therapeutic effects. TRIAL REGISTRATION NUMBER jRCTs061200030.
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Affiliation(s)
- Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Okayama, Japan
| | | | | | - Takumi Ota
- Mochida Pharmaceutical Co., Ltd, Tokyo, Japan
| | | | - Ryo Katsumata
- Department of Health Care Medicine, Kawasaki Medical School, Okayama, Japan
| | - Minoru Fujita
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Okayama, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School, Okayama, Japan
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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2
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Mousavi T, Nikfar S, Abdollahi M. An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome. Expert Opin Drug Metab Toxicol 2020; 16:583-604. [PMID: 32380874 DOI: 10.1080/17425255.2020.1767067] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Irritable bowel syndrome (IBS), globally affecting 11.2% of the population and imposing a direct annual cost of $1.7bn-$10bn in the US, is one of the today's major therapeutic challenges. Therefore, there is urgent need to address this issue through reviewing the tolerability and efficacy of available medications. AREAS COVERED Over the past decade, related experiments were cited through Clinicaltrials.gov, PubMed, WHO ICTRP, and Cochrane library. Pharmacological parameters of approved medications available in the USFDA, EMA, TGA and PMDA were also stated. EXPERT OPINION Anti-spasmodics are used as the first-line treatment in pain-predominant IBS and IBS-D, among which calcium channel blockers and neurokinin-type 2 receptor antagonists seem to replace anti-cholinergic drugs. As second-line treatments, rifaximin is considered to be the best for IBS-D though it has lower efficacy than alosetron and eluxadoline. For IBS-C, linaclotide is the most effective and the safest second-line therapy, following laxatives/fibers, which may be replaced by tenapanor, in the future. When moderate to severe IBS is associated with severe pain or comorbid psychological disorders, gut-brain neuromodulators could also be prescribed. Regarding all this, there is still a paramount need to conduct careful clinical studies on efficacy, safety and cost-effectiveness of current approved and non-approved treatments.
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Affiliation(s)
- Taraneh Mousavi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences , Tehran, Iran.,Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran
| | - Shekoufeh Nikfar
- Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences , Tehran, Iran.,Evidence-Based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, Pharmaceutical Sciences Research Center (PSRC), and The Pharmaceutical Management and Economics Research Center (PMERC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences , Tehran, Iran.,Department of Pharmacoeconomics and Pharmaceutical Administration, School of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences , Tehran, Iran.,Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran.,Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences , Tehran, Iran
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3
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Masuy I, Pannemans J, Tack J. Irritable bowel syndrome: diagnosis and management. MINERVA GASTROENTERO 2020; 66:136-150. [DOI: 10.23736/s1121-421x.19.02640-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
Introduction: As an analogue of uroguanylin plecanatide binds to the Guanylate Cyclase-C receptor activating fluid and ion secretion in the small intestine with the same pH-dependent binding kinetics as the natural ligand. Plecanatide has been FDA approved as safe and effective for the indications of Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with Constipation (IBS-C).Areas covered: All clinical trial results supporting approval of plecanatide in IBS-C are reported, evaluated and interpreted in the context of the complex pathophysiology of functional diseases and the barriers that must be overcome for appropriate protocol design and conduct.Expert opinion: The Expert Opinion section discusses safety and efficacy of plecanatide for IBS-C. Broader consideration of some of the inherent challenges in understanding and treating functional gastrointestinal disorders includes: 1. the difficulty of understanding diseases with complex pathophysiology that clinically present with a few simple symptoms, 2. exploring the pathophysiology of functional diseases using pharmacophysiology, 3. value of 'Set Theory' in the evaluation of complex clinical data and 4. physiologic and pathophysiologic insight gained by evaluation 'physiologic redundancy' and 'conservation of function'.
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Affiliation(s)
- Philip B Miner
- Oklahoma Foundation for Digestive Research, Oklahoma City, OK, USA
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5
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Abstract
Constipation, a condition characterized by heterogeneous symptoms, is common in Western society. It is associated with reduced physical health, mental health, and social functioning. Because constipation is rarely due to a life-threatening disease (for example, colon cancer), current guidelines recommend empiric therapy. Limited surveys suggest that fewer than half of treated individuals are satisfied with treatment, perhaps because the efficacy of drugs is limited, they are associated with undesirable side effects, or they may not target the underlying pathophysiology. For example, although a substantial proportion of constipated patients have a defecatory disorder that is more appropriately treated with pelvic floor biofeedback therapy than with laxatives, virtually no pharmacological trials formally assessed for anorectal dysfunction. Recent advances in investigational tools have improved our understanding of the physiology and pathophysiology of colonic and defecatory functions. In particular, colonic and anorectal high-resolution manometry are now available. High-resolution anorectal manometry, which is increasingly used in clinical practice, at least in the United States, provides a refined assessment of anorectal pressures and may uncover structural abnormalities. Advances in our understanding of colonic molecular physiology have led to the development of new therapeutic agents (such as secretagogues, pro-kinetics, inhibitors of bile acid transporters and ion exchangers). However, because clinical trials compare these newer agents with placebo, their efficacy relative to traditional laxatives is unknown. This article reviews these physiologic, diagnostic, and therapeutic advances and focuses particularly on newer therapeutic agents.
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Affiliation(s)
- David O. Prichard
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA
| | - Adil E. Bharucha
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program and Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA
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6
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Tack J, Corsetti M, Camilleri M, Quigley EM, Simren M, Suzuki H, Talley NJ, Tornblom H, Van Oudenhove L. Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts. Gut 2018; 67:1425-1433. [PMID: 28814481 DOI: 10.1136/gutjnl-2016-312230] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 06/07/2017] [Accepted: 06/09/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances. METHODS A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs. RESULTS Five criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism. CONCLUSION Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.
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Affiliation(s)
- Jan Tack
- Translational Research Center for Gastrointestinal Disorders, KULeuven, Leuven, Belgium
| | - Maura Corsetti
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Michael Camilleri
- CENTER Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Eamonn Mm Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA
| | - Magnus Simren
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Nicholas J Talley
- Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia
| | - Hans Tornblom
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lukas Van Oudenhove
- Translational Research Center for Gastrointestinal Disorders, KULeuven, Leuven, Belgium
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Abstract
BACKGROUND The options for the treatment of diarrhea and constipation are evolving as emerging therapies target small bowel receptors. The goal of this review is to discuss small bowel receptors involved in intestinal absorption, secretion, and motility. The review highlights therapies already approved or currently being studied for the modulation of these receptors. METHODS The articles cited in this review focus on the molecular level of pathways involved in diarrhea and constipation, and highlight the respective pharmacotherapies. RESULTS The majority of the studies in the current literature investigate the effects of both the small and large intestine receptors on diarrhea and constipation. There are fewer studies that isolate the effects of these receptors solely on the small bowel, and focusing more on the receptors found distinctly in the small intestine may be an area of interest for future studies as this can inspire more targeted therapies.
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Affiliation(s)
- Elizabeth S John
- Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, 1 RWJ Place, New Brunswick, NJ, 08901, USA.
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Sinagra E, Morreale GC, Mohammadian G, Fusco G, Guarnotta V, Tomasello G, Cappello F, Rossi F, Amvrosiadis G, Raimondo D. New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond. World J Gastroenterol 2017; 23:6593-6627. [PMID: 29085207 PMCID: PMC5643283 DOI: 10.3748/wjg.v23.i36.6593] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 04/15/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.
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Affiliation(s)
- Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
- Euro-Mediterranean Institute of Science and Technology, 90100 Palermo, Italy
- Department of Experimental Biomedicine and Clinical Neuroscience, Section of Human Anatomy, University of Palermo, 90100 Palermo, Italy
| | | | - Ghazaleh Mohammadian
- Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institutet, Karolinska University Hospital, Huddinge, 17176 Stockholm, Sweden
| | - Giorgio Fusco
- Unit of Internal Medicine, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, 90100 Palermo, Italy
| | - Valentina Guarnotta
- Section of Cardio-Respiratory and Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine, University of Palermo, Palermo 90127, Italy
| | - Giovanni Tomasello
- Euro-Mediterranean Institute of Science and Technology, 90100 Palermo, Italy
- Department of Experimental Biomedicine and Clinical Neuroscience, Section of Human Anatomy, University of Palermo, 90100 Palermo, Italy
| | - Francesco Cappello
- Euro-Mediterranean Institute of Science and Technology, 90100 Palermo, Italy
- Department of Experimental Biomedicine and Clinical Neuroscience, Section of Human Anatomy, University of Palermo, 90100 Palermo, Italy
| | - Francesca Rossi
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
| | - Georgios Amvrosiadis
- Unit of Gastroenterology, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, 90100 Palermo, Italy
| | - Dario Raimondo
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
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彭 颖, 李 晓. 倍半萜内酯类治疗肠易激综合征的应用前景. Shijie Huaren Xiaohua Zazhi 2017; 25:1624-1632. [DOI: 10.11569/wcjd.v25.i18.1624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
肠易激综合征(irritable bowel syndrome, IBS)是常见的功能性肠道疾病, 以腹痛或腹部不适、排便习惯异常为特征, 其发病机制尚不明确. 依照罗马Ⅲ标准可将其分为腹泻型、便秘型、混合型和未定型4种亚型. 目前临床治疗原则主要是对症治疗, 迄今尚无特效药物能够有效治疗所有类型IBS. 倍半萜内酯类成分是众多药用植物的生物活性成分, 具有广泛生物学活性, 包括抗肿瘤、抗炎镇痛、抗菌等. 本文就倍半萜内酯类成分可改善IBS症状的相关生物学活性, 及其在IBS治疗中的应用前景进行简要综述.
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10
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Abstract
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.
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Affiliation(s)
- Mellar Davis
- Cleveland Clinic Lerner School of Medicine Case, Western Reserve University, 9500 Euclid Avenue, T34, Cleveland, OH, 44195, USA.
- Clinical Fellowship Program, Cleveland, OH, USA.
- Palliative Medicine and Supportive Oncology Services, Taussig Cancer Institute, Cleveland, OH, USA.
| | - Pamela Gamier
- Cleveland Clinic Lerner School of Medicine Case, Western Reserve University, 9500 Euclid Avenue, T34, Cleveland, OH, 44195, USA
- Clinical Fellowship Program, Cleveland, OH, USA
- Palliative Medicine and Supportive Oncology Services, Taussig Cancer Institute, Cleveland, OH, USA
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11
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Abstract
Despite being one of the most common conditions leading to gastroenterological referral, irritable bowel syndrome (IBS) is poorly understood. However, recent years have seen major advances. These include new understanding of the role of both inflammation and altered microbiota as well as the impact of dietary intolerances as illuminated by magnetic resonance imaging (MRI), which has thrown new light on IBS. This article will review new data on how excessive bile acid secretion mediates diarrhea and evidence from post infectious IBS which has shown how gut inflammation can alter gut microbiota and function. Studies of patients with inflammatory bowel disease (IBD) have also shown that even when inflammation is in remission, the altered enteric nerves and abnormal microbiota can generate IBS-like symptoms. The efficacy of the low FODMAP diet as a treatment for bloating, flatulence, and abdominal discomfort has been demonstrated by randomized controlled trials. MRI studies, which can quantify intestinal volumes, have provided new insights into how FODMAPs cause symptoms. This article will focus on these areas together with recent trials of new agents, which this author believes will alter clinical practice within the foreseeable future.
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Affiliation(s)
- Robin Spiller
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
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Li F, Fu T, Tong WD, Liu BH, Li CX, Gao Y, Wu JS, Wang XF, Zhang AP. Lubiprostone Is Effective in the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Mayo Clin Proc 2016; 91:456-68. [PMID: 27046523 DOI: 10.1016/j.mayocp.2016.01.015] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Revised: 12/28/2015] [Accepted: 01/12/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the efficacy and safety of lubiprostone in the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). PATIENTS AND METHODS We performed a literature search of the MEDLINE, Cochrane, Google Scholar, and ClinicalTrials.gov databases (from January 1, 2005, through January 31, 2015). Relevant studies meeting the inclusion criteria were manually searched by 2 independent reviewers. Efficacy outcomes evaluated at 1 week, 1 month, and 3 months of intervention were weekly frequency of spontaneous bowel movements, severity of constipation, consistency of stools, degree of abdominal pain/discomfort, degree of straining, and abdominal bloating. RESULTS Of 246 studies identified, data from 9 trials comprising 1468 patients (63.6%) in the lubiprostone group and 841 (36.4%) in the placebo group were analyzed. We found that lubiprostone treatment significantly improved the severity of constipation, stool consistency, abdominal pain, degree of straining, and abdominal bloating at 1 week (P≤.03) and 1 month (P≤.004), except for abdominal pain at 1 month, which was similar to that when treated with placebo (P=.21). At 3 months, except for abdominal bloating (P=.03), there was no difference between lubiprostone and placebo groups in all other outcomes (P≥.05). Adverse effects such as nausea, vomiting, and diarrhea were common (incidence rate, 2.4%-75%); however, the incidence of serious adverse effects was low (<5%) and was mostly unrelated to lubiprostone treatment. CONCLUSION Lubiprostone is a safe and efficacious drug for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, with limited adverse effects in 3 months of follow-up.
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Affiliation(s)
- Fan Li
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Tao Fu
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Wei-Dong Tong
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Bao-Hua Liu
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Chun-Xue Li
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Yu Gao
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Jin-Song Wu
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Xiang-Feng Wang
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - An-Ping Zhang
- Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
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Peng Y, Wang S, Wang M, Wang F, Yang J, Wu C, Li X. Dual effects on constipation and diarrhea: protective potential of Radix Inulae lactones on irritable bowel syndrome. RSC Adv 2016. [DOI: 10.1039/c6ra18533a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Radix Inulae (RI) is commonly used to treat upper body pain, emesis, diarrhea and parasitic diseases in China.
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Affiliation(s)
- Ying Peng
- School of Pharmacy
- Shanghai Jiao Tong University
- Shanghai 200240
- China
| | - Siqi Wang
- School of Pharmacy
- Shanghai Jiao Tong University
- Shanghai 200240
- China
- Department of Pharmacology
| | - Mengyue Wang
- School of Pharmacy
- Shanghai Jiao Tong University
- Shanghai 200240
- China
| | - Fang Wang
- Department of Pharmacology
- Shenyang Pharmaceutical University
- Shenyang
- China
| | - Jingyu Yang
- Department of Pharmacology
- Shenyang Pharmaceutical University
- Shenyang
- China
| | - Chunfu Wu
- Department of Pharmacology
- Shenyang Pharmaceutical University
- Shenyang
- China
| | - Xiaobo Li
- School of Pharmacy
- Shanghai Jiao Tong University
- Shanghai 200240
- China
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14
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Soufi-Afshar I, Moghadamnia A, Bijani A, Kazemi S, Shokri-Shirvani J. Comparison of pyridostigmine and bisacodyl in the treatment of refractory chronic constipation. CASPIAN JOURNAL OF INTERNAL MEDICINE 2016; 7:19-24. [PMID: 26958328 PMCID: PMC4761118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Treatment of chronic constipation is creating one of the major problems for doctors and patients. Pyridostigmine increases the gastrointestinal motility through the effects on cholinesterase. It seems that this mechanism can reduce chronic constipation. The aim of this study was to compare the effects of pyridostigmine and bisacodyl on chronic constipation. METHODS This study was conducted on 68 patients who suffered from chronic constipation. Patients were randomly divided into two groups of Pyridostigmine and bisacodyl in which each consisted of 34 patients, respectively. Bristol stool form score, straining defecation, the time of defecation, the number of defecation per week, sense of incomplete evacuation and self-digitation were collected by means of questionnaires and the data were compared. RESULTS Sixty-eight patients with the mean age of 68.12±84.49 were studied. The mean difference in the frequency of defecation per week, VAS score, the time to defecation and the Bristol Stool form Scale in pre and post-treatment were 4.33±1.88, 5.96±2.29, 12.30±7.95 min and 2.10±0.95 in pyridostigmine group and 2.96±1.81, 4.06±2.22, 6.67±5.23 min and 1.41±0.84 in bisacodyl group, respectively. The significant difference was observed in both pyridostigmine and bisacodyl groups (P=0.005, P=0.002, P=0.002 and P=0.005, respectively). 60% and 32.3 of patients in pyridostigmine and bisacodyl groups recovered from self-digitations, respectively. In pyridostigmine and bisacodyl groups, 66.7% and 32.3 of them had improvement in the sense of incomplete defecation, respectively. CONCLUSION Pyridostigmine and bisacodyl significantly improved the symptoms of chronic constipation similarly.
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Affiliation(s)
- Iman Soufi-Afshar
- Department of Internal Medicine, Babol University of Medical Sciences, Babol, Iran.
| | | | - Ali Bijani
- Social Determinant of Health Research Center - Health Research Institute - Babol University of Medical Sciences, Babol, Iran.
| | - Sohrab Kazemi
- Cellular & Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran
| | - Javad Shokri-Shirvani
- Department of Internal Medicine, Babol University of Medical Sciences, Babol, Iran. ,Correspondence: Javad Shokri-Shirvani, Department of Internal Medicine, Babol University of Medical Sciences, Babol, Iran
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Bielefeldt K, Levinthal DJ, Nusrat S. Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis. J Neurogastroenterol Motil 2015; 22:31-45. [PMID: 26717930 PMCID: PMC4699720 DOI: 10.5056/jnm15171] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 11/20/2015] [Accepted: 12/03/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS The marketing of newer agents for treatment of constipation and irritable bowel syndrome with constipation (IBS-C) emphasize improvements in abdominal pain. However, it is not clear whether this observation reflects a unique visceral analgesic effect of these agents or is a general feature of effective laxation. We sought to determine the relationship between improvements in bowel frequency and decreases in abdominal pain in clinical trials of patients with constipation or IBS-C. METHODS We searched "PubMed" and "Embase" databanks for clinical trials in patients with constipation or IBS-C, targeting publications that provided detailed data on bowel movement frequency and pain intensity before and after an intervention. We abstracted the results and performed meta-analytic and meta-regression analyses. RESULTS Twenty-seven trials (16 constipation and 11 IBS) met entry criteria. Baseline weekly bowel movement frequency was low with 2.35 (2.07-2.64) with differences between constipation (2.00 [1.62-2.38]) and IBS-C (2.77 [2.40-3.14]; Q = 8.18; P = 0.002). Studies reported moderate pain levels (2.12 [1.81-2.42]) with comparable baseline levels in constipation (2.02 [1.63-2.42]) and IBS-C (2.35 [2.10-2.60]; Q = 1.92; P = 0.167). Treatments increased bowel frequency by 2.17 [1.88-2.47] and lowered pain ratings by 0.58 [0.49-0.68]. Meta-regression demonstrated a significant correlation between treatment-induced increases in bowel frequency and decreased pain ratings. CONCLUSIONS Our analysis suggests that reduction of abdominal pain observed in clinical trials of constipation and IBS-C is associated with laxation, and may not require specific drug mechanisms, thus arguing against a unique advantage of newer agents over traditional laxatives in the treatment of constipation and IBS-C.
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Affiliation(s)
| | | | - Salman Nusrat
- University of Oklahoma Health Sciences Center, Oklahoma, OK, USA
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Quigley EMM, Neshatian L. Advancing treatment options for chronic idiopathic constipation. Expert Opin Pharmacother 2015; 17:501-11. [PMID: 26630260 DOI: 10.1517/14656566.2016.1127356] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Chronic constipation is a global problem affecting all ages and associated with considerable morbidity and significant financial burden for society. Though formerly defined on the basis of a single symptom, infrequent defecation; constipation is now viewed as a syndrome encompassing several complaints such as difficulty with defecation, a sense of incomplete evacuation, hard stools, abdominal discomfort and bloating. AREAS COVERED The expanded concept of constipation has inevitably led to a significant change in outcomes in clinical trials, as well as in patient expectations from new therapeutic interventions. The past decades have also witnessed a proliferation in therapeutic targets for new agents. Foremost among these have been novel prokinetics, a new category, prosecretory agents and innovative approaches such as inhibitors of bile salt transport. In contrast, relatively few effective therapies exist for the management of those anorectal and pelvic floor problems that result in difficult defecation. EXPERT OPINION Though constipation is a common and often troublesome disorder, many of those affected can resolve their symptoms with relatively simple measures. For those with more resistant symptoms a number of novel, effective and safe options now exist. Those with defecatory difficulty (anismus, pelvic floor dysfunction) continue to represent a significant management challenge.
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Affiliation(s)
- Eamonn M M Quigley
- a Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology , Houston Methodist Hospital, Weill Cornell Medical College , Houston , TX , USA
| | - Leila Neshatian
- a Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology , Houston Methodist Hospital, Weill Cornell Medical College , Houston , TX , USA
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Yin Y, Zhong L, Wang JW, Zhao XY, Zhao WJ, Kuang HX. Tong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P. World J Gastroenterol 2015; 21:4536-4546. [PMID: 25914462 PMCID: PMC4402300 DOI: 10.3748/wjg.v21.i15.4536] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 12/09/2014] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model.
METHODS: Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.
RESULTS: Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P < 0.001). However, the defecation frequency was significantly decreased (3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time (in seconds) of colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation.
CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.
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Awad RA, Camacho S, Flores F, Altamirano E, García MA. Rectal tone and compliance affected in patients with fecal incontinence after fistulotomy. World J Gastroenterol 2015; 21:4000-4005. [PMID: 25852287 PMCID: PMC4385549 DOI: 10.3748/wjg.v21.i13.4000] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 10/15/2014] [Accepted: 11/19/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the anal sphincter and rectal factors that may be involved in fecal incontinence that develops following fistulotomy (FIAF).
METHODS: Eleven patients with FIAF were compared with 11 patients with idiopathic fecal incontinence and with 11 asymptomatic healthy subjects (HS). All of the study participants underwent anorectal manometry and a barostat study (rectal sensitivity, tone, compliance and capacity). The mean time since surgery was 28 ± 26 mo. The postoperative continence score was 14 ± 2.5 (95%CI: 12.4-15.5, St Mark’s fecal incontinence grading system).
RESULTS: Compared with the HS, the FIAF patients showed increased rectal tone (42.63 ± 27.69 vs 103.5 ± 51.13, P = 0.002) and less rectal compliance (4.95 ± 3.43 vs 11.77 ± 6.9, P = 0.009). No significant differences were found between the FIAF patients and the HS with respect to the rectal capacity; thresholds for the non-noxious stimuli of first sensation, gas sensation and urge-to-defecate sensation or the noxious stimulus of pain; anal resting pressure or squeeze pressure; or the frequency or percentage of relaxation of the rectoanal inhibitory reflex. No significant differences were found between the FIAF patients and the patients with idiopathic fecal incontinence.
CONCLUSION: In patients with FIAF, normal motor anal sphincter function and rectal sensitivity are preserved, but rectal tone and compliance are impaired. The results suggest that FIAF is not due to alterations in rectal sensitivity and that the rectum is more involved than the anal sphincters in the genesis of FIAF.
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Shin A, Acosta A, Camilleri M, Boldingh A, Burton D, Ryks M, Rhoten D, Zinsmeister AR. A randomized trial of 5-hydroxytryptamine4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation. Clin Gastroenterol Hepatol 2015; 13:701-8.e1. [PMID: 25148765 DOI: 10.1016/j.cgh.2014.08.012] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Accepted: 08/04/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS YKP10811, a selective agonist of the serotonin 5-hydroxytryptamine-4 receptor, increases gastrointestinal (GI) motility. We investigated the safety and effects of YKP10811 on GI and colonic transit and bowel movements (BMs) in patients with functional constipation in a randomized, double-blind, placebo-controlled study. METHODS Patients with functional constipation, based on the Rome III criteria, were assigned randomly to groups given YKP10811 10 mg (n = 15), 20 mg (n = 16), 30 mg (n = 15), or placebo (n = 11) daily for 8 days. Transit of solids was measured by validated scintigraphy at baseline and on days 7 to 9. Patients kept diaries on days 1 to 9, recording time to first BM, number of BMs/day, and stool consistency (based on the Bristol Stool Form Scale). To evaluate safety, we collected data on adverse events and clinical laboratory test and electrocardiograms results. The primary efficacy end points were determined from an intent-to-treat analysis assessing colonic transit at 24 hours and the half-time (t1/2) of gastric emptying, using analysis of covariance models. Secondary efficacy end points included measures of colonic transit (geometric center at 4 and 24 hours), small-bowel transit (based on colon filling at 6 hours), t1/2 of ascending colon emptying, and bowel functions. We used the Dunnett test to compare the effects of each dose with placebo. A per-protocol analysis (PPA) assessed the t1/2 of gastric emptying and time to first BM using proportional hazards models. RESULTS Fifty-five participants completed the study. YKP10811 was associated with a significant acceleration in colon filling at 6 hours (P < .05), t1/2 of ascending colon emptying, and colonic transit at 24 and 48 hours, as well as increased stool consistency over 8 days (based on intent-to-treat analysis). In general, the 10-mg and 20-mg doses were the most effective in accelerating colonic transit. No serious adverse events were observed. CONCLUSIONS YKP10811, a selective agonist of the serotonin receptor 5-hydroxytryptamine-4, accelerates GI and colonic transit and improves bowel functions in patients with functional constipation, compared with placebo. ClinicalTrial.Gov: NCT01523184.
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Affiliation(s)
- Andrea Shin
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Andres Acosta
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota.
| | - Amy Boldingh
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Duane Burton
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Michael Ryks
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Deborah Rhoten
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Alan R Zinsmeister
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C. E. N. T. E. R.), College of Medicine, Mayo Clinic, Rochester, Minnesota
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Rossi M, Merello M, Perez-Lloret S. Management of constipation in Parkinson's disease. Expert Opin Pharmacother 2014; 16:547-57. [PMID: 25539892 DOI: 10.1517/14656566.2015.997211] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Constipation is a frequent non-motor feature of Parkinson's disease (PD). It is the most common gastrointestinal symptom of the disease and it can precede motor symptoms by as much as 20 years. Constipation can produce discomfort and affect activities of daily living, productivity and quality of life, thus warranting early diagnosis and treatment. AREAS COVERED In this review, the safety and efficacy of traditional and novel strategies for constipation management will be discussed. A treatment algorithm for constipation in PD will be presented. EXPERT OPINION Polyethylene glycol and lubiprostone are first-line compounds recommended by evidence-based medicine guidelines for the treatment of constipation due to slow colonic transit in PD. Management of constipation secondary to defecatory dysfunction due to pelvic floor dyssynergia can be done by levodopa or apomorphine injections, botulinum toxin type A injection into the puborectalis muscle, and nonpharmacological interventions, like biofeedback therapy or functional magnetic stimulation, which showed some benefit in PD patients with constipation, but in general more extensive studies are warranted.
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Affiliation(s)
- Malco Rossi
- Raul Carrea Institute for Neurological Research (FLENI), Neuroscience Department, Movement Disorders Section , Buenos Aires , Argentina
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Foley A, Burgell R, Barrett JS, Gibson PR. Management Strategies for Abdominal Bloating and Distension. Gastroenterol Hepatol (N Y) 2014; 10:561-571. [PMID: 27551250 PMCID: PMC4991532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Bloating and distension are among the most common gastrointestinal complaints reported by patients with functional gut disorders and by the general population. These 2 complaints are also among the most prevalent of the severe symptoms reported by patients with irritable bowel syndrome. Nonetheless, only a limited number of published studies have specifically addressed bloating; it is infrequently studied as a primary endpoint, and what little systematic information exists has often been garnered from the assessment of secondary endpoints or the dissection of composite endpoints. This lack of data, and our consequent limited understanding of the pathophysiology of bloating, had hampered the quest for effective and targeted therapies until recently. Advances in the knowledge of underlying mechanisms, particularly with regard to the roles of diet, poorly absorbed fermentable carbohydrates, dysbiosis of the gut bacteria, alterations in visceral hypersensitivity, and abnormal viscerosomatic reflexes, have enabled the development of improved treatment options. The most significant recent advance has been a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which significantly reduces patients' symptoms and improves quality of life. Given the prevalence of bloating and its perceived severity, it is clear that further studies regarding the pathogenesis and treatment of this problem are needed.
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Affiliation(s)
- Anna Foley
- Dr Foley and Dr Burgell are gastroenterologists, Dr Barrett is a dietitian, and Dr Gibson is a professor and the director of the Department of Gastroenterology at Monash University and Alfred Hospital in Melbourne, Victoria, Australia
| | - Rebecca Burgell
- Dr Foley and Dr Burgell are gastroenterologists, Dr Barrett is a dietitian, and Dr Gibson is a professor and the director of the Department of Gastroenterology at Monash University and Alfred Hospital in Melbourne, Victoria, Australia
| | - Jacqueline S Barrett
- Dr Foley and Dr Burgell are gastroenterologists, Dr Barrett is a dietitian, and Dr Gibson is a professor and the director of the Department of Gastroenterology at Monash University and Alfred Hospital in Melbourne, Victoria, Australia
| | - Peter R Gibson
- Dr Foley and Dr Burgell are gastroenterologists, Dr Barrett is a dietitian, and Dr Gibson is a professor and the director of the Department of Gastroenterology at Monash University and Alfred Hospital in Melbourne, Victoria, Australia
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Abstract
The perception of pain in children is easily influenced by environmental factors and psychological comorbidities that are known to play an important role in its origin and response to therapy. Chronic abdominal pain is one of the most commonly treated conditions in modern pediatric gastroenterology and is the hallmark of 'functional' disorders that include irritable bowel syndrome, functional dyspepsia, and functional abdominal pain. The development of pharmacological therapies for these disorders in adults and children has been limited by the lack of understanding of the putative, pathophysiological mechanisms that underlie them. Peripheral and central pain-signaling mechanisms are known to be involved in chronic pain originating from the gastrointestinal tract, but few therapies have been developed to target specific pathways or enhance correction of the underlying pathophysiology. The responses to therapy have been variable, potentially reflecting the heterogeneity of the disorders for which they are used. Only a few small, randomized clinical trials have evaluated the benefit of pain medications for chronic abdominal pain in children and thus, the decision on the most appropriate treatment is often based on adult studies and empirical data. This review discusses the most common, non-narcotic pharmacological treatments for chronic abdominal pain in children and includes a thorough review of the literature to support or refute their use. Because of the dearth of pediatric studies, the focus is on pharmacological and alternative therapies where there is sufficient evidence of benefit in either adults or children with chronic abdominal pain.
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Affiliation(s)
- Adrian Miranda
- Division of Gastroenterology and Hepatology, Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA,
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Jadallah KA, Kullab SM, Sanders DS. Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies. World J Gastroenterol 2014; 20:8898-8909. [PMID: 25083062 PMCID: PMC4112860 DOI: 10.3748/wjg.v20.i27.8898] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 03/23/2014] [Accepted: 06/05/2014] [Indexed: 02/07/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS (IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.
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Abstract
OBJECTIVE Gastrointestinal disturbances as a result of changes in eating patterns have been described in eating disorders. Many patients who experience irritable bowel syndrome report changes in eating patterns as a way to cope with their symptoms. Little is known about the consequences of these practices. The aim of this study was to explore whether repeated eating restriction (defined as not eating ≥ 4 hours while hungry) is associated with motility disturbances. METHODS Of 17 patients with irritable bowel syndrome, subjects were divided into those who habitually restrict their eating (n = 8) and those without eating restriction (n = 9) (age range 15-21, mean 19.2; 64.7% girls). Whole-gut transit time was measured by radiopaque markers, gastric sensitivity was measured by water load test (drinking max of 800 mL of water in 5 minutes or until full), and gastric dysrhythmias by an electrogastrogram. RESULTS Restrictors drank less water (mean 464.4 mL) than nonrestrictors (mean 613 mL; P = 0.02). No difference was found in gastric dysrhythmias (62.5% vs 77.8%; P = 0.5). Whole-gut transit tended to be slower in the restrictors (mean 51.0 hours) than in nonrestrictors (mean 37.5 hours), but this was not significant. CONCLUSIONS Eating restriction appears to be associated with increased gastric sensation. More data are needed from larger studies to determine whether eating behaviors are associated with other motility disturbances.
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Abstract
PURPOSE OF REVIEW Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are highly prevalent medical conditions that reduce quality of life and represent a substantial economic burden on healthcare cost. Until recently, no specific treatment options were available. This review will provide an update of the most recent randomized clinical trials data showing efficacy and safety of novel, targeted treatment modalities in IBS and CIC with gastrointestinal receptor and ion channel agonists. RECENT FINDINGS Recent discoveries of peptides and small molecules targeting gastrointestinal receptors and ion channels resulted in novel, specific pharmacological therapies of IBS and CIC. The bicyclical fatty acid lubiprostone and the synthetic 14-amino acid peptide linaclotide were identified to selectively activate a Chloride Channel-2 and the Guanylin Cyclase-C receptor, respectively, and demonstrate efficacy in the treatment of IBS with constipation and CIC. SUMMARY Novel molecules including the bicyclical fatty acid lubiprostone and the synthetic 14-amino acid peptide linaclotide represent new treatment modalities for IBS with constipation and CIC with proven efficacy and acceptable side-effect profiles.
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Affiliation(s)
- Supriya Rao
- Boston University School of Medicine, Section of Gastroenterology, Boston, Massachusetts, USA
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Raschi E, De Ponti F. Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome. Expert Opin Drug Metab Toxicol 2014; 10:293-305. [PMID: 24387275 DOI: 10.1517/17425255.2013.876410] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Lubiprostone acts locally (apical membrane of human intestinal epithelial cells) as a highly selective type-2 chloride channel activator. It was approved in the USA for chronic idiopathic constipation (January 2006) and in women aged ≥ 18 years suffering from irritable bowel syndrome with constipation (IBS-C) (April 2008). So far, the only other pro-secretory medication approved in IBS-C and currently available in USA and Europe (since August and November 2012, respectively) is linaclotide. AREAS COVERED This review outlines the regulatory history, pharmacokinetic, pharmacodynamic and safety data in the treatment of IBS-C with a European perspective. It is based on publicly available data, namely, published literature, drug labels and the FDA's spontaneous reporting system. EXPERT OPINION Although interesting pharmacodynamic data suggest that lubiprostone may have additional mechanisms of action, its beneficial effects in IBS-C must be confirmed in the actual clinical scenario taking into account the new version of European Medicines Agency's guideline. This is especially important with regard to duration of studies (recommended to be at least 6 months) to adequately assess long-term sustained efficacy, withdrawal, rebound and safety. Further research is warranted in uncertain areas (i.e., males, pediatric and elderly patients). On the basis of current data, it is still too early to draw definite conclusions on the overall risk-benefit balance for IBS-C.
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Affiliation(s)
- Emanuel Raschi
- University of Bologna, Department of Medical and Surgical Sciences, Pharmacology Unit, Alma Mater Studiorum , Via Irnerio, 48, I-40126 Bologna BO , Italy
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Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a complex syndrome that is difficult to manage. Here we present the evidence supporting medication treatments for specific IBS symptoms, discuss evidence-based management of IBS with medications including dose regimens and adverse effects and review progress on research for new IBS treatments. SUMMARY Currently, there is evidence to support improvements in specific IBS symptoms following treatment with loperamide, psyllium, bran, lubiprostone, linaclotide, amitriptyline, trimipramine, desipramine, citalopram, fluoxetine, paroxetine, dicyclomine, peppermint oil, rifaximin, ketotifen, pregabalin, gabapentin and octreotide and there are many new medications being investigated for the treatment of IBS. Key Message: Of the medications with demonstrated improvements for IBS symptoms, rifaximin, lubiprostone, linaclotide, fiber supplementation and peppermint oil have the most reliable evidence supporting their use for the treatment of IBS. Onset of efficacy for the various medications has been noted to be as early as 6 days after initiation; however, the efficacy of most medications was not assessed prospectively at predefined periods. Additional studies of currently available and new medications are ongoing and are needed to better define their place in therapy and expand therapeutic options for the treatment of IBS. The most promising new medications for IBS include a variety of novel pharmacologic approaches, most notably the dual μ-opioid receptor agonist and δ-opioid antagonist, JNJ-27018966.
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Affiliation(s)
- Katy E Trinkley
- University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colo., USA
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Hasler WL, Owyang C. Challenges of managing pain in constipation-predominant IBS: clinical perspectives on antinociceptive actions of linaclotide. Gastroenterology 2013; 145:1196-9. [PMID: 24409483 DOI: 10.1053/j.gastro.2013.10.039] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Kojima R, Nozawa K, Doihara H, Keto Y, Kaku H, Yokoyama T, Itou H. Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced constipation and visceral pain. Eur J Pharmacol 2013; 723:288-93. [PMID: 24291101 DOI: 10.1016/j.ejphar.2013.11.020] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Revised: 10/17/2013] [Accepted: 11/03/2013] [Indexed: 12/26/2022]
Abstract
Constipation is a major gastrointestinal motility disorder with clinical need for effective drugs. We previously reported that transient receptor potential ankyrin 1 (TRPA1) is highly expressed in enterochromaffin (EC) cells, which are 5-hydroxytryptamine (5-HT)-releasing cells, and might therefore be a novel target for constipation. Here, we examined the effects of ASP7663, a novel and selective TRPA1 agonist, in constipation models as well as an abdominal pain model. ASP7663 activated human, rat, and mouse TRPA1 and released 5-HT from QGP-1 cells, and oral but not intravenous administration of ASP7663 significantly improved the loperamide-induced delay in colonic transit in mice. While pretreatment with the TRPA1 antagonist HC-030031 and vagotomy both inhibited the ameliorating effect of oral ASP7663 on the colonic transit, both orally and intravenously administered ASP7663 significantly inhibited colorectal distension (CRD)-induced abdominal pain response in rats. Taken together, these results demonstrate that ASP7663 exerts both anti-constipation and anti-abdominal pain actions, the former is likely triggered from the mucosal side of the gut wall via activation of vagus nerves while the latter is assumed to be provoked through systemic blood flow. We conclude that ASP7663 can be an effective anti-constipation drug with abdominal analgesic effect.
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Affiliation(s)
- Ryosuke Kojima
- Pharmacology Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
| | - Katsura Nozawa
- Pharmacology Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
| | - Hitoshi Doihara
- Pharmacology Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
| | - Yoshihiro Keto
- Pharmacology Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
| | - Hidetaka Kaku
- Chemistry Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
| | - Toshihide Yokoyama
- Pharmacology Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
| | - Hiroyuki Itou
- Pharmacology Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
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Open channels for functional bowel disorders: guanylate cyclase C agonists in IBS and CC. Dig Dis Sci 2013; 58:2446-8. [PMID: 23812864 DOI: 10.1007/s10620-013-2766-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Abstract
INTRODUCTION Chronic constipation (CC) is a common problem worldwide and, for some sufferers, a cause of considerable morbidity. Recent definitions of CC have moved from the former emphasis on stool frequency alone to a broader concept that strives to encompass the various symptoms that may bother afflicted individuals. Accordingly, new therapies attempt to not only increase frequency of defecation but also to address such symptoms as satisfaction with bowel action, straining, bloating, and distension. AREAS COVERED To provide context the relative merits and problems related to conventional laxative-based approaches to constipation are first reviewed and then more recent novel pharmacological approaches to the management of constipation assessed. The focus is on two classes of compounds, selective prokinetics and prosecretory agents, and studies on their efficacy and safety in chronic idiopathic constipation were retrieved and evaluated. EXPERT OPINION While undoubtedly effective, high-quality evidence to support laxatives, the traditional remedies for constipation, is remarkably scarce due, in large part, to the absence, until very recently, of high-quality randomized controlled clinical trials. The selective prokinetic agent prucalopride and the prosecretory agents lubiprostone and linaclotide have shown efficacy and been associated with a good safety record in large well-conducted clinical studies. Other novel approaches, such as the inhibition of ileal bile salt absorption, offer particular promise.
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Bharucha AE, Low P, Camilleri M, Veil E, Burton D, Kudva Y, Shah P, Gehrking T, Zinsmeister AR. A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation. Gut 2013; 62:708-15. [PMID: 22677718 PMCID: PMC3924965 DOI: 10.1136/gutjnl-2012-302483] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. This study evaluated the effects of a cholinesterase inhibitor on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation. DESIGN After a 9-day baseline period, 30 patients (mean ± SEM age 50 ± 2 years) with diabetes mellitus (18 type 1, 12 type 2) and chronic constipation without defaecatory disorder were randomised to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose or 120 mg three times a day; this dose was maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function were evaluated at baseline and the final 3 and 7 days of treatment, respectively. Treatment effects were compared using analysis of covariance, with gender, body mass index and baseline colonic transit as covariates. RESULTS 19 patients (63%) had moderate or severe autonomic dysfunction; 16 (53%) had diabetic retinopathy. 14 of 16 patients randomised to pyridostigmine tolerated 360 mg daily; two patients took 180 mg daily. Compared with placebo (mean ± SEM 1.98 ± 0.17 (baseline), 1.84 ± 0.16 (treatment)), pyridostigmine accelerated (1.96 ± 0.18 (baseline), 2.45 ± 0.2 units (treatment), p<0.01) overall colonic transit at 24 h, but not gastric emptying or small-intestinal transit. Treatment effects on stool frequency, consistency and ease of passage were significant (p ≤ 0.04). Cholinergic side effects were somewhat more common with pyridostigmine (p=0.14) than with placebo. CONCLUSIONS Cholinesterase inhibition with oral pyridostigmine accelerates colonic transit and improves bowel function in diabetic patients with chronic constipation.
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Affiliation(s)
- Adil E Bharucha
- Clinical and Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
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Awad RA, Santillán MC, Camacho S, Blanco MG, Domínguez JC, Pacheco MR. Rectal hyposensitivity for non-noxious stimuli, postprandial hypersensitivity and its correlation with symptoms in complete spinal cord injury with neurogenic bowel dysfunction. Spinal Cord 2013; 51:94-98. [PMID: 22929208 DOI: 10.1038/sc.2012.98] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
STUDY DESIGN Prospective clinical study. OBJECTIVES To assess fasting and postprandial (PP) perception of rectal distension and its correlation with symptoms in patients with spinal cord injury (SCI) and neurogenic bowel dysfunction compared to ten healthy subjects (HS). SETTING Experimental Medicine and Motility Unit, Mexico General Hospital and National Institute of Rehabilitation. METHODS Twenty patients with complete SCI at cervical, thoracic and lumbar levels [American Spinal Injury Association (ASIA) A] were studied. Rectal sensitivity was evaluated with a barostat. RESULTS In SCI patients, while lower the rectal tone more time was used for defecate (R=0.50, P=0.048) and more PP episodes of fecal incontinence occur (R=0.54, P=0.030). The thresholds for non-noxious stimuli of first (23.6 mmHg, CI 19.5-27.7) vs 14.0 (CI 10.9-17.1), P=0.004; gas (27.9 mmHg, CI 19.9-35.8) vs 17.9 mmHg (CI 14.25-21.69), P=0.02 and urge-to-defecate sensation (33.2 mmHg, CI 27.5-38.8) vs 22.4 mmHg (CI 17.9-26.9), P=0.01 were reported by SCI patients at higher pressure than HS, respectively. SCI patients reported PP pain sensation at a lower pressure than controls (27.8 mmHg, CI 21.5-34.2 vs 36.5 mmHg, CI 31.8-41.2), P=0.04. CONCLUSION SCI patients preserve rectal sensation, present rectal hyposensitivity for non-noxious stimuli and PP hypersensitivity. Lower rectal tone was related to the time used for defecate and with fecal incontinence. The results suggest that an intact neural transmission between the spinal cord and higher centres is indispensable for noxious stimulus, but not for non-noxious stimuli. Also, barostat sensitivity studies can complement ASIA criteria to verify a complete injury.
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Affiliation(s)
- R A Awad
- Experimental Medicine and Motility Unit, Gastroenterology Service U-107, Mexico City General Hospital, México, DF, México.
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Mozaffari S, Nikfar S, Abdollahi M. Metabolic and toxicological considerations for the latest drugs used to treat irritable bowel syndrome. Expert Opin Drug Metab Toxicol 2013; 9:403-21. [PMID: 23330973 DOI: 10.1517/17425255.2013.759558] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The high prevalence of irritable bowel syndrome (IBS), a chronic gastrointestinal (GI) disorder, its lack of satisfactory effective drugs and its complicated pathophysiology lead to the demand of new therapeutic agents. During a new drug development process, the pharmacokinetic profiling is of a great considerable importance comparable to drug's efficacy. This involves the drug's absorption, distribution, metabolism and excretion, all of which are crucial to its usefulness. In addition, the toxicological profile and possible adverse reactions of the drug should be identified. Also its interactions should be identified at different phases of trials. Several pharmacokinetic studies are carried out to achieve drugs with the best absorption and bioavailability and the least adverse effects and lowest toxicity. AREAS COVERED To make an update on new clinically introduced drugs for IBS and their dynamics and kinetics data, the present systematic review was accomplished. All relevant bibliographic databases were searched from the year 2003 up to May 2012 to identify all clinical trials that evaluated the potential efficacy of a novel agent in IBS. EXPERT OPINION Some evaluated drugs, such as ramosetron (5-HT3 antagonist) and pexacerfont (CRF1 receptor antagonist), have shown some benefits in diarrhea-predominant IBS (D-IBS), while, prucalopride and mosapride (5-HT4 agonist) with prokinetic effect were found useful in constipation-predominant IBS (C-IBS). Besides, dexloxiglumide, lubiprostone and linaclotide have shown beneficial effects in C-IBS patients. Melatonin regulates GI tract motility and, asimadoline, gabapentin and pregabalin show reduction of pain threshold and visceral hypersensitivity. Glucagon-like peptide analog, calcium-channel blockers and neurokinin receptor antagonists have shown benefits in pain attacks. More time is required to indicate both efficacy and safety in long-term treatment due to multifactorial pathophysiology, variations in individual responses and insufficient assessment methods, which limit the right decision-making process about the efficacy and tolerability of these new drugs.
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Affiliation(s)
- Shilan Mozaffari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
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Abstract
INTRODUCTION Elobixibat (formerly A3309) is a first-in-class ileal bile acid transporter (IBAT) inhibitor for treatment of chronic idiopathic constipation (CIC; syn functional constipation). CIC affects up to 25% of the general population; and up to a half are unsatisfied with current therapies. There is an unmet need for safe and effective drugs to treat CIC. AREAS COVERED The authors present: i) an overview of Phase II clinical trials of elobixibat in CIC, based on peer-reviewed literature and congress presentations and ii) an evaluation of the efficacy and mechanism of action of elobixibat in the treatment of CIC. EXPERT OPINION Elobixibat provides a novel approach to treat chronic constipation via IBAT inhibition with enhanced delivery of bile acids to the colon. Pharmacodynamic studies show that it accelerates colonic transit, increases stool frequency, loosens stool consistency and relieves constipation-related symptoms in CIC patients. These beneficial effects are maintained for a minimum of 8 consecutive weeks of treatment. With minimal absorption and low systemic bioavailability, elobixibat is generally well tolerated and may offer the added benefit of improving serum lipid profiles through bile acid depletion.
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Affiliation(s)
- Banny S Wong
- College of Medicine, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN 55905, USA
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Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors. BMC Pharmacol 2012; 12:3. [PMID: 22553939 PMCID: PMC3403872 DOI: 10.1186/1471-2210-12-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2011] [Accepted: 05/03/2012] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. Stressors damage the epithelial cell barrier and cellular homeostasis leading to loss of these functions. Effects of active linaclotide on repair of barrier and cell function in pig jejunum after ischemia and in T84 cells after treatment with proinflammatory cytokines, interferon-γ and tumor necrosis factor-α were examined. Comparison with effects of lubiprostone, known to promote repair of barrier function was carried out. RESULTS In ischemia-damaged pig jejunum, using measurements of transepithelial resistance, (3)H-mannitol fluxes, short-circuit current (Cl(-) secretion) and occludin localization, active linaclotide failed to effectively promote repair of the epithelial barrier or recovery of short-circuit current, whereas lubiprostone promoted barrier repair and increased short-circuit current. In control pig jejunum, 1 μM linaclotide and 1 μM lubiprostone both caused similar increases in short-circuit current (Cl(-) secretion). In T84 cells, using measurements of transepithelial resistance, fluxes of fluorescent macromolecules, occludin and mitochondrial membrane potential, active linaclotide was virtually ineffective against damage caused by interferon-γ and tumor necrosis factor-α, while lubiprostone protected or promoted repair of epithelial barrier and cell function. Barrier protection/repair by lubiprostone was inhibited by methadone, a ClC-2 inhibitor. Linaclotide, but not lubiprostone increased [cGMP]i as expected and [Ca(2+)]i and linaclotide depolarized while lubiprostone hyperpolarized the T84 plasma membrane potential suggesting that lubiprostone may lead to greater cellular stability compared to linaclotide. In T84 cells, as found with linaclotide but not with lubiprostone, transepithelial resistance was slightly but significantly decreased by guanylin, STa and 8-bromo cGMP and fluorescent dextran fluxes were increased by guanylin. However the physiological implications of these small but statistically significant changes remain unclear. CONCLUSIONS Considering the physiological importance of epithelial barrier function and cell integrity and the known impact of stressors, the finding that lubiprostone, but not active linaclotide, exhibits the additional distinct property of effective protection or repair of the epithelial barrier and cell function after stress suggests potential clinical importance for patients with impaired or compromised barrier function such as might occur in IBS.
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Soubra M, Schey R. Lubiprostone for the treatment of adult women with irritable bowel syndrome with constipation. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2012; 5:23-30. [PMID: 24833931 PMCID: PMC3987758 DOI: 10.4137/cgast.s7625] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Irritable bowel syndrome with constipation (IBS-C) affects approximately 5% of the population in western countries. The majority of those afflicted are women. Symptoms are often detrimental to the individual's quality of life and incur high healthcare costs to society. There is no evidence to support changes in lifestyle, laxatives or over the counter supplements. Tegaserod appeared to have promising results but was promptly removed from the market due to adverse cardiovascular events. In 2008, lubiprostone (Amitiza) was approved by the US Food and Drug Administration (FDA) for the treatment of women with IBS-C. It is thought to selectively activate type 2 chloride channels in the apical membrane of the intestinal epithelial cells leading to chloride secretion. As result, sodium and water are passively secreted generating peristalsis and laxation, without stimulating gastrointestinal smooth muscle. Several trials with predominantly female patients have shown it to be effective in the treatment of IBS-C. Overall lubiprostone was safe, well tolerated and associated with mostly benign side effects. Nausea and diarrhea were the most commonly reported. Though there are no head to head comparisons with other pharmacological agents, it is our opinion that lubiprostone should be tried as a first line pharmacotherapy for women with IBS-C at a dose of 8 μg BID. Thus far, lubiprostone offers a welcome approach to our narrow therapeutic armamentarium. Further understanding of its mechanism of action may provide additional insight into the pathophysiology of IBS-C.
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Affiliation(s)
- Mahmoud Soubra
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Ron Schey
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa
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