西沙必利在肠易激综合征（便秘型）治疗中的应用

研究西沙必利在治疗肠易激综合征中的作用效果，方法根据肠易激棕合征的诊断标准选出７０例患者，给予西沙必利１０ｍｇ／次，每日３次，１月为１疗程，每周随访１次。结果：３７例完全缓解，１７例部分缓解，１６例未缓解，有效率为７７．１６％。结论西沙必怕易激综合征是有效的。     

中医外治法治疗便秘型肠易激综合征研究进展

便秘型肠易激综合征以腹痛、排便异常为主要临床表现。在我国总体发病率为1.4%～11.5%,中医外治法在便秘型肠易激综合征治疗方面取得重要进展,包括针刺、灸法、穴位贴敷、中药灌肠等治疗,操作方便、安全性高且疗效好。本文旨在论述便秘型肠易激综合征的中医外治法,以为临床诊治提供参考。     

Lubiprostone获准用于治疗女性便秘型肠易激综合征

据报道,美国FDA已经批准苏坎泊制药公司（Sucampo Pharmaceuticals）开发的慢性便秘治疗药Amitiza（通用名：lubiprostone）增加一项适应证——女性便秘型肠易激综合征（C—IBS）,这是目前唯一一个被批准用于该病的药物。     

用于非便秘型肠易激综合征的药物Xifaxan

Salix制药公司近期宣布其开发的广谱抗生素Xifaxan(rifaximin)的两项Ⅲ期临床研究获得了阳性结果.在这两项大规模、多中心、各由600名非便秘型肠易激综合征(IBS)患者参加的研究中,受试者接受Xifaxan 550 mg或安慰剂,每日3次,共2周.     

肠嗜铬细胞及其分泌的5-羟色胺在肠易激综合征中的作用

肠易激综合征(irritable bowelsyndrom e,IBS)是一组包括腹痛或腹部不适、排便习惯改变和大便性状异常,持续存在或间歇发作,而又缺乏形态学和生化异常改变可资解释的症候群。按症状大致可以分为腹泻为主型(diarrhea-predom inantIBS,D-IBS)、便秘为主型(constipation-predom inantIBS,C-IBS)、腹泻便秘交替型(alernating IBS,A-IBS)。近十多年来,人们已普遍公认IBS是一种感觉、动力紊乱所致的肠功能性疾病。胃肠运动功能障碍、内脏高敏感性和精神心理因素是IBS最重要的病理生理特征。目前观点认为IBS患者的腹痛、胃肠运动功能…     

疏香灸法治疗便秘型肠易激综合征的临床观察

目的探讨疏香灸法治疗便秘型肠易激综合征的临床疗效。方法研究对象为2009年8月至2010年8月我院收治的76例便秘型肠易激综合征患者,随机分为治疗组及对照组,每组38例。对照组给予莫沙必利片西药治疗(5mg/次,3次/天),治疗组给予疏香灸法治疗。观察两组患者的临床疗效、症状改善及患者满意度情况。结果治疗组总有效率为94.7%,患者满意率为92.1%;对照组总有效率为68.5%,患者满意率为63.2%,两组均有显著差异(P<0.05);且两组治疗前各项症状积分无显著差异(P>0.05),治疗后治疗组均显著低于对照组(P<0.05)。结论疏香灸法治疗便秘型肠易激综合征,疗效确切,可显著缓解症状,有助于患者的早日康复。     

中西医结合治疗便秘型肠易激综合征的临床观察

目的：分析便秘型肠易激综合征的临床诊治情况。方法：本院接收肠易激综合征患者86例,中西医结合治疗,并用统计分析方法比较有效率。结果：治疗组的治愈率和总有效率都明显高于对照组。结论：便秘型肠易激综合征的病因和发病机制未能明晰,发病是由多因素引起的,本研究体现了中西医药结合的优势。     

莫沙必利联合福松治疗便秘型肠易激综合征临床观察

目的对莫沙必利联合福松治疗便秘为主型IBS(C-IBS)患者的效果进行了短期疗效观察。方法选择30例C-IBS进行随机对照试验。治疗组口服莫沙必利5mg、3次/d以及福松每次10g,2次/d;对照组口服莫沙必利5mg、3次/d。初诊时均口服14d,以后在有临床症状时服药。分别在治疗前(0d)、治疗后7d、14d、28d对腹痛或腹部不适、排便频率和粪便性状改变等症状记分。结果治疗前后比较,治疗组各项症状均明显改善(P<0.01),而对照组在第28d症状改善不明显(P>0.05)。两组间腹痛缓解情况在第7日和第14日无明显差异(P>0.05),而在第28日治疗组缓解率明显高于对照组(P=0.01);冶疗组粪便性状和粪便频率的缓解情况明显优于对照组(P<0.05),两组间总有效率第7日、14日差异无显著性(P>0.05)而在第28日治疗组明显高于对照组(P=0.028)。结论单用莫沙必利可能会缓解便秘型IBS的临床症状,而莫沙必利和福松联合应用,则可能取得明显的效果,莫沙必利和福松联合应用,可作为C-IBS治疗的一种较好选择。     

肠易激综合征患者乙状结肠黏膜内5-羟色胺的作用

目的研究肠易激综合征（IBS）患者结肠黏膜5-羟色胺的分布情况,进一步探讨两者之间的关系。方法选择腹泻型和便秘型IBS患者和健康对照者,在电子肠镜下取升结肠、乙状结肠以及直肠黏膜活检,采用免疫组化方法观察5-羟色胺在结肠黏膜中的分布情况。结果与对照组相比,便秘组结肠5-羟色胺分布差异无统计学意义（P〉0.05）。腹泻组升结肠段、直肠段5-羟色胺多于对照组,但无统计学意义（P〉0.01）;乙状结肠段5-羟色胺分布明显多于对照组（P〈0.05）。结论腹泻型IBS乙状结肠5-羟色胺分布明显增多,说明乙状结肠5-羟色胺增多可能在腹泻型IBS的发病机制中起重要作用。     

用于治疗便秘型肠易激综合征和慢性便秘的药物Linaclotide

肠易激综合征（IBS）为最常见的功能性胃肠病之一,其症状常表现为腹痛、腹泻、便秘及腹胀等。约有1／3的IBS患者同时患有便秘,即便秘型肠易激综合征（IBS—c）。该病症的常规治疗方案包括软便药Stoolsoftener和缓泻药。在美国,目前唯一获准用于IBS-C治疗的药物为Sueampo制药公司和武田制药公司（Takeda）合作开发的氯离子通道激活剂Amitiza（lubiprostone）,     

Alosetron and irritable bowel syndrome

Alosetron (Lotronex^®, GlaxoSmithKline) is a potent and selective 5-HT₃-receptor antagonist approved by the FDA for the treatment of women with diarrhoea-predominant irritable bowel syndrome (IBS) in whom conventional therapy has failed. Studies involving healthy volunteers and IBS patients have demonstrated a beneficial effect of treatment with alosetron on global IBS symptoms, abdominal pain and discomfort, altered bowel function as well as improvement of quality of life (QOL). Data from animals studies suggest the involvement of 5-HT₃ receptors on intrinsic primary afferent neurons in the mediation of the effect of alosetron on gastrointestinal motility and secretion. While definitive proof of a visceroanalgesic action is not available, an additional central mechanism of action is suggested by findings obtained in animal models, as well as from human brain imaging studies. Alosetron shows a greater effectiveness in women, and the role of genetic factors underlying inter-individual differences in the response to alosetron is currently under investigation. The most frequent adverse event associated with the use of alosetron is constipation and in some rare cases, the development of colonic mucosal ischaemia. In the following review, the most recent reported effects of alosetron on gastrointestinal motility, visceral sensitivity and anxiety, both in terms of preclinical and clinical data will be discussed. The impact of alosetron on QOL in IBS patients and the safety of treatment with alosetron, will also be covered.     

Review of tegaserod in the treatment of irritable bowel syndrome

Tegaserod is a drug in a new class of compounds called aminoguanidine indoles and is structurally similar to serotonin (5-HT) with modifications that make the drug selective for the 5-HT₄ receptor. Tegaserod has a stimulatory effect on gastrointestinal (GI) motility that has been demonstrated in animal studies and in healthy adults. Tegaserod also increases GI secretion and reduces rectal sensitivity. Tegaserod is currently approved by the FDA for the treatment of women with constipation-predominant irritable bowel syndrome (C-IBS). Eight large Phase III clinical trials involving > 5000 IBS patients support the clinical efficacy of tegaserod in this group of patients. Patients who were treated with tegaserod had an overall improvement in IBS symptoms (Subject’s Assessment of Global Relief) as well as in secondary end points, such as abdominal pain and discomfort, stool consistency, change in bowel movements and relief of bloating. Tegaserod was well-tolerated. The most common adverse reaction in clinical trials was diarrhoea, which was usually temporary and mild, although severe diarrhoea requiring hospitalisation has been rarely (< 1%) reported.     

Dexloxiglumide for the treatment of constipation predominant irritable bowel syndrome

Introduction: Irritable bowel syndrome (IBS) is a multifactorial functional gut disorder, where sensory/motor disturbances seem to play a major role, with no satisfactory treatment for a majority of patients. Cholecystokinin (CCK) is a hormone with several effects on gastrointestinal function, and IBS patients have been shown to produce altered sensory/motor responses to CCK.

Areas covered: Dexloxiglumide is a selective antagonist of the type 1 receptor of CCK, which has demonstrated to revert the CCK mediated effects on gastrointestinal motility and sensitivity. In humans, Dexloxiglumide has been shown to accelerate gastric emptying, slow down transit in the proximal colon, and increase the tolerance to intestinal gas. In phase 2 clinical trials Dexloxiglumide 200 mg tid has demonstrated to be superior to placebo in symptom relief in constipation predominant IBS (IBS-C). In a phase 3 withdrawal study Dexloxiglumide obtained a more sustained effect than placebo. However, these promising effects in IBS-C have not been confirmed in large phase 3 studies so far.

Expert opinion: Dexloxiglumide has demonstrated positive effects on important aspects of gastrointestinal function, like gastric emptying and gas tolerance, that deserves consideration in future studies. However, the available data is insufficient to recommend dexloxiglumide for treatment of IBS-C today.     

Serotonergic modulation and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a debilitating disease, which is characterised by recurrent abdominal cramping and pain, and is associated with either constipation and/or diarrhoea. It is approximately twice as prevalent in women as it is in men and is among the most common gastrointestinal (GI) disorders encountered in primary care. The aetiology of the disease is poorly understood but may include motility dysregulation, visceral sensitivity, inflammation, bacterial infection, dietary antigens, psychological stress, GI surgery or a gut-brain phenomenon. At present, there is no acceptable treatment for IBS, although recent advances indicate that some relief may be achieved by the administration of compounds that act on 5-HT (serotonin) receptors. This suggestion is the result of numerous studies which have shown that 5-HT may exert a number of diverse effects on human GI tissues. In addition, it has emerged that the levels of the 5-HT metabolite (5-HIAA) are raised in the plasma of IBS patients and that administration of 5-HT-like compounds may mimic the symptoms of IBS. It has therefore been proposed that therapy with compounds that act at 5-HT receptors will return the intestine to normal activity and alleviate the pain experienced by these patients. One compound (alosetron, a 5-HT₃ receptor antagonist) has already been released onto the market but showed benefit in female patients only and only in those whose primary symptom was diarrhoea. In addition, the compound was recently withdrawn following concerns over its safety. The reasons why alosetron only appears to show efficacy in females, why these treatments are only effective in a subset of the population of IBS patients and why alosetron elicits its particular side effect profile have not been elucidated. One further serotonergic compound, tegaserod (Zelmac?, a 5-HT₄ receptor agonist), has shown promise for the treatment of patients with constipation-predominant IBS and is currently in pre-registration for this indication. It is clear, however, that further research will have to take place before the utility of serotonergic modulation in the treatment of IBS can be fully validated.     

Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome

Renzapride is a novel drug currently under clinical evaluation for the treatment of irritable bowel syndrome (IBS). Renzapride is a mixed 5-hydroxytryptamine type 4 (5-HT₄) agonist and 5-HT₃ receptor antagonist that has a stimulatory effect on gastrointestinal motility and transit, as established by in vivo and in vitro studies. Its therapeutic efficacy, tolerability and safety have been evaluated in diabetic gastroparesis in a single study, as well as in IBS in a few other studies. Phase II studies indicated potential beneficial effects on symptoms and bowel habits in patients with constipation-predominant IBS and mixed-type IBS. The outcome of Phase III studies is currently under evaluation.     

Novel therapies in the treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is characterised by abnormalities in motility, sensation and perception. It is one of the most common conditions encountered in clinical practice, especially by gastroenterologists. Pharmacological treatment of IBS is aimed at the predominant symptom and recent advances in pathophysiology has opened the door to the development of new compounds that target specific receptors. During this review, the most promising investigational and recently approved drugs will be discussed.     

Efficacy and safety of plecanatide in treating constipation predominant irritable bowel syndrome

Introduction: Uroguanylin interacting with intestinal Guanylate Cyclase C (GC-C) receptors plays an important role in gastrointestinal fluid and electrolyte homeostasis. Plecanatide is the first uroguanylin analog that stimulates GC-C receptors on gastrointestinal mucosa with pH-sensitive receptor binding. Binding to the GC-C receptor activates intracellular conversion of GTP to cGMP resulting in the stimulation of intestinal fluid secretion.

Areas covered: Herein, all published research regarding the development of and clinical experience with plecanatide is reviewed. Clinical study results in patients with Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with Constipation (IBS-C) are also reviewed. Success in the treatment of CIC and IBS-C is supported by beneficial effects on stool viscosity, Complete Spontaneous Bowel Movements and visceral sensation. Finally, the discussion within focuses on the importance of plecanatide in understanding the physiology of uroguanylin, the pathophysiology of IBS-C and the potential for development of uroguanylin and guanylin analogs.

Expert opinion: Given this broad spectrum of potential activity for GC-C agonists, it would not be surprising to see that the use of agents such as plecanatide in new areas grow to a level even greater than the use for the present CIC and IBS-C indications.     

Safety evaluation of lubiprostone in the treatment of constipation and irritable bowel syndrome

Introduction: Lubiprostone is approved in the United States for the treatment of chronic idiopathic constipation and constipation predominant irritable bowel syndrome (IBS-C). Lubiprostone causes secretion of fluid and electrolytes in the small bowel, through the activation of chloride channels, and thereby induces laxation and improvement of bowel functions. It is generally considered to be safe and effective. Common side effects of lubiprostone include nausea, diarrhea, abdominal pain and bloating, and the rare side effect dyspnea. Likely mechanisms for these side effects may be related to lubiprostone's primary action on small bowel secretion and the associated intestinal distension, as well as smooth muscle contraction.

Areas covered: This article reviews the pharmacokinetic and safety profile of lubiprostone, with particular relevance to the two FDA-approved dosages.

Expert opinion: Lubiprostone acts topically in the gut lumen and is almost completely metabolized in the gut lumen. Lubiprostone's M3 metabolite can be detected in low concentrations in the serum and may be responsible for some of its side effects. However, the exact mechanisms by which the side effects are produced are currently unknown.     

Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome

Introduction: Irritable bowel syndrome diarrhea predominant (IBS-D) is a highly prevalent GI disease, affecting nearly a third of all patients diagnosed with irritable bowel syndrome. Current treatment options are limited.

Areas covered: This review discusses the pharmacotherapeutic options for IBS-D including currently used medications, the two newly FDA approved medications, as well as emerging therapies with potential benefit in IBS-D. Particular emphasis is placed on rifaximin and eluxadoline and their possible use in IBS-D.

Expert Opinion: Current pharmacological treatment of IBS-D includes loperamide, bile acid sequestrants, antispasmodics, tricyclic antidepressants, alosetron, eluxadoline and rifaximin. The latter two treatments have significantly added to the pharmacotherapeutic options for patients suffering from IBS-D.     

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.