Lubiprostone: chronic constipation and irritable bowel syndrome with constipation

Lubiprostone is a bicyclic fatty acid metabolite analogue of prostaglandin E1. The FDA has approved lubiprostone for the treatment of chronic constipation in men and women and the treatment of women with irritable bowel syndrome with constipation (IBS-C). Lubiprostone specifically activates type-2-chloride channels on the apical membrane of epithelial cells. Lubiprostone acts locally within the intestinal tract, is rapidly metabolized and has very low systemic bioavailability. Animal studies have demonstrated that lubiprostone increases gastrointestinal fluid secretion in a dose-dependent manner. Clinical studies performed in men and women with chronic constipation using 24 μg of lubiprostone twice-daily demonstrated objective improvement in stool frequency and consistency, as well as symptoms of straining and incomplete evacuation. A multi-center study of patients with IBS-C found that 8 μg of lubiprostone twice-daily improved both global and individual symptoms of irritable bowel syndrome. Lubiprostone is generally well tolerated and serious adverse events are rare. The most common reported side effects are nausea, headache and diarrhea. This monograph provides a brief overview on chloride channel function in the gastrointestinal tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses the safety and efficacy of this new medication for the treatment of chronic constipation and IBS-C.     

8招解除便秘烦恼

"给你的肠子洗洗澡。"无论大江南北,地铁公交,某润肠茶的广告词总是不忘提醒人们便秘的苦和难。其实,对付便秘没有单一的一种灵丹妙药。找准原因,找对方法,调整饮食才是解决便秘的关键所在。     

抗生素致便秘

患者男,78岁。因咳嗽、咳痰1周,于2003年11月19日入院。患者既往有冠心病,心律失常,偶发室性早搏史15年,高血压病史6年,脑梗塞3年,颈椎病多年。入院查体:T36.5℃,精神尚可,咽红,扁桃体不大,双肺呼吸音粗,偶闻哮鸣音,未闻湿啰音仄盒姆挝醇斐!Q9妫籛BC6.76×109·L-1,N0.72。入院诊断:支气管炎。给予克林霉素磷酸酯1.2g静滴,2次/d。第2天,患者因腹胀、无便意要求停用克林霉素。随后连续3日未排便,给予麻仁润肠九1粒口服,第4日排干燥成团块状大便1次。经应用氨溴索(沐舒坦)、羧甲司坦(霸灵)等药物治疗后,患者于11月29日痊愈出院。出…     

数字化排粪造影在顽固性便秘患者中的临床应用

目的 探讨数字化排粪造影在顽固性便秘患者的临床应用.方法 回顾性分析60例顽固性便秘患者进行的数字化排粪造影检查资料,通过测量肛直角、肛上距、乙耻距和小耻距、肛管长度、肛直间距、骶骨及骶尾曲率等指标,得出相关疾病的诊断.结果 25例次(41.7%)为会阴下降,16例次(26.7%)为直肠前壁黏膜脱垂,37例次(61.7%)为直肠内套叠,12例次(20%)为直肠外脱垂,47例次(78.3%)为直肠膨出或称直肠前突,13例次(21.6%)为盆底痉挛综合征,39例次(65%)为耻骨直肠肌肥厚症,11例次(18.3%)为盆底疝,12例次(20%)为骶直分离,10例次(16.7%)为内括约肌失迟缓症.结论 数字化排粪造影对顽固性便秘患者相关疾病的阳性检出率达10种之多,可为临床提供有价值的诊断参考.     

便秘方治疗慢性功能性便秘临床观察

目的:观察便秘方治疗慢性功能性便秘的临床疗效。方法:120例慢性功能性便必患者随机分为治疗组和对照组。对照组采用聚乙二醇电解质散剂治疗,治疗组采用我院自制便秘方治疗。结果:治疗组痊愈、显效、有效、无效及治疗总有效率分别为25%(15例)、58.33%(35例)、8.33%(5例)、8.33%(5例)及91.67%(55例),对照组痊愈、显效、有效、无效及治疗总有效率分别为8.33%(5例)、40%(24例)、30%(18例)、21.67%(13例)及78.33%(47例),组间比较差异显著(P<0.05),便秘方临床疗效优于聚乙二醇电解质散剂。结论:便秘方治疗慢性功能性便秘疗效优于聚乙二醇电解质散剂。     

乳果糖在孕妇便秘中的疗效观察

目的观察乳果糖治疗孕妇便秘的临床疗效及安全性。方法选择在我院门诊就诊的54例孕妇便秘患者,随机平均分为2组。研究组(27例)给予乳果糖溶液口服治疗,对照组(27例)给予心理、饮食干预。治疗14 d后观察两组的临床疗效,同时评价乳果糖的安全性。结果研究组总有效率高于对照组(96.3%vs.74.1%,P<0.05)。研究组干预期间出现腹泻1例,腹胀1例,均较轻微,经调整乳果糖用量后好转,未影响治疗过程。对照组无不良反应发生。结论乳果糖在治疗孕妇便秘方面临床疗效确切,安全可靠,值得临床推广。     

Prucalopride for constipation

Importance of the field: Chronic constipation has a high prevalence, and current medical and pharmacological therapies do not restore normal bowel function in all patients.

Areas covered in the review: A PubMed search (1965 – 2009) using the following terms alone or in combination: prucalopride, 5-HT₄, R093877, safety, toxicity, pharmacokinetics, pharmacodynamics, transit, cardiac, hERG, arrhythmia, potassium current, elderly.

What the reader will gain: Understanding of the mechanisms of action, safety, efficacy and indications for prucalopride in patients with chronic constipation.

Take home message: Prucalopride is an efficacious and generally safe, new therapeutic option in the management of chronic constipation.     

排粪造影51例临床应用研究

目的研究排粪造影对便秘的诊断价值。方法对51例便秘患者行排粪造影检查。结果直肠前凸32例,盆底痉挛综合征13例,耻骨直肠肌综合征3例,会阴下降35例,直肠粘膜脱垂2例,直肠内套叠2例,直肠外脱垂1例,内脏下垂9例,肠疝1例,骶直分离9例,未见异常2例。结论排粪造影检查对功能性出口梗阻病变的诊断价值明显优于传统的钡灌肠和内窥镜等检查。     

Longitudinal direct medical costs associated with constipation in women

Aliment Pharmacol Ther 2011; 33: 251–260

Summary

Background Although direct medical costs for constipation‐related medical visits are thought to be high, to date, there have been no studies examining longitudinal resource utilisation in adults with constipation. Aim To estimate the incremental direct medical costs associated with constipation in women. Methods This is a nested case‐control study. The study population consisted of all mothers of 5718 children in the population‐based birth cohort born during 1976–1982 in a community. The cases presented to the medical facilities with constipation. The controls were randomly selected and matched to cases in a 2:1 ratio. Direct medical costs for constipated women and controls were collected for the years 1987–2002. Results We identified 168 women with a diagnosis of constipation. The total direct medical costs over the 15‐year period for constipated subjects were more than double those of controls [$63 591 (95% CI: 49 786–81 396) vs. $24 529 (95% CI: 20 667–29 260)]. The overall out‐patient costs for constipated women were $38 897 (95% CI: 31 381–48 253) compared to $15 110 (95% CI: 12 904–17 781) for controls. The median of annual out‐patient visits for constipated women was 0.16 compared to 0.11 for controls. Conclusion Women with constipation have significantly higher medical care utilisation and expenditures compared with women without constipation.     

Use of prucalopride in adults with chronic idiopathic constipation

ABSTRACT

Introduction: Prucalopride is a selective 5-HT₄ receptor agonist with colonic prokinetic activity. It was recently approved by the FDA for the treatment of chronic idiopathic constipation. Before this approval, there were limited options to improve colonic motility in the treatment of chronic idiopathic constipation.

Areas covered: We systematically searched PubMed, Embase, ClinicalTrials.gov, and international conference presentations, and we reviewed all studies that evaluated prucalopride for the treatment of chronic idiopathic constipation in adults. In this review, we discuss the pharmacokinetics, pharmacodynamics, receptor interactions, phase I-IV clinical trials, and safety outcomes of prucalopride in adults, including the elderly.

Expert opinion: Prucalopride is an effective agent to improve colonic motility, decrease colonic transit time, and increase complete spontaneous bowel movements in patients with chronic idiopathic constipation. Unlike previously available 5-HT₄ receptor agonists such as cisapride and tegaserod, prucalopride does not interact with the cardiac hERG potassium channels or other serotonergic receptors in blood vessels and is not associated with an increase in major adverse cardiovascular events. Additionally, prucalopride has demonstrated promise in the treatment of gastroparesis, post-operative ileus, and opioid-induced constipation. Prucalopride directly stimulates colonic motility, differentiating it from all other medications (exclusively osmotic or chloride secretagogues) approved for chronic constipation in the last decade.     

Managing constipation in children

Constipation, defined as difficulty, delay or pain on defaecation, is common in children and is often difficult to manage. Here, we review the assessment and treatment of affected children and the support that they, and their families, may need.     

冠心病患者便秘的原因分析

目的 分析冠心病患者便秘的原因.方法 收集2010年5月至2013年5月北京市大兴区人民医院心内科门诊以及病房冠心病便秘患者80例（便秘组）,同时收集同期体格检查健康者50例作为正常对照组.采用自制问卷调查的方式了解冠心病便秘患者的排便次数、性状、排便习惯、方式、膳食结构、活动锻炼等情况.结果 便秘组与正常对照组定时排便习惯,排便方式、环境的改变,每天饮水（＞1 500 ml）者占比差异有统计学意义[28.8％ （23/80）比76.0％ （38/50）,67.5％（54/80）比44.0％（22/50）,36.2％（29/80）比62.0％（31/50）]（P=0.000,P=0.008,P=0.004）;便秘组和正常对照组食用水果、蔬菜者占比差异无统计学意义[43.8％（35/80）比60.0％ （30/50）]（P=0.071）;每天适量活动者比例便秘组和正常对照组间差异无统计学意义[47.5％（38/80）比54.0％ （27/50）]（P=0.471）.结论 冠心病患者便秘的发生与排便和饮食习惯密切相关,故建立良好的排便以及饮食习惯可预防冠心病患者便秘的发生.     

功能性便秘患者情绪和睡眠状况的分析

目的 探讨功能性便秘对患者情绪和睡眠状况的影响.方法 选取2012年1月～2013年1月来本院进行治疗的功能性便秘患者245例,对所有患者行罗马Ⅲ功能性胃肠病心理社会报警问卷调查,调查患者的情绪与睡眠情况.分析患者情绪和睡眠状况与便秘的关系,同时对患者进行随机分组,分为实验组和对照组,对照组仅给予常规通便药物治疗,实验组给予调整情绪＋改善睡眠状况＋通便药物治疗,观察两组的治疗效果.结果 245例患者中,58.0％（142/245）的患者近期感到情绪紧张,59.2％（145/245）的患者近期感到情绪沮丧或低落,50.2％（123/245）的患者同时存在以上两种情绪；33.1％（81/245）的患者经常感到情绪紧张,30.2％ （74/245）的患者经常感到情绪沮丧或低落.54.7％（134/245）的患者认为便秘与情绪有关,39.6％（97/245）的患者认为便秘与睡眠有关.便秘病程长于情绪异常者占69.8％（67/96）,便秘先于睡眠障碍者占68.2％（86/126）.治疗后,实验组患者每周排便次数增加（1.7±0.4）次,对照组增加（1.2±0.3）次,两组比较差异有统计学意义（P＜0.05）.结论 功能性便秘患者常合并情绪异常及睡眠障碍,通过心理干预综合治疗,可显著改善患者的情绪及睡眠状况,有利于提高功能性便秘的疗效,值得临床推广应用.