Rifaximin for the treatment of diarrhoea-predominant irritable bowel syndrome

Introduction: Rifaximin is a non-absorbable, semisynthetic antibiotic that acts as an inhibitor of bacterial RNA synthesis, with a broad spectrum of antibacterial activity. Due to its poor absorption, rifaximin has an increased exposure to the intestine, thus it is suitable for the treatment of many gastrointestinal (GI) diseases. In irritable bowel syndrome (IBS) pathogenesis, gut microbiota impairment may play a major role. The possibility of modulating intestinal bacteria using antibiotics, in particular, rifaximin, has been demonstrated to improve IBS symptoms in non-constipation subtypes of IBS.

Areas covered: We reviewed the use of rifaximin in diarrhoea-predominant IBS, focusing on its pharmacokinetic characteristics, its absorption in GI disease, its lack of interaction with other drugs and its new extended release formulation.

Expert opinion: Rifaximin, with its low systemic absorption and no clinically significant interactions with other drugs, may represent a treatment of choice for IBS, mainly due to its ability to act on IBS pathogenesis, through the modulation of gut microbiota. Further studies to analyse the effect of rifaximin treatment on the composition of faecal microbiota are warranted. In particular, they need to evaluate whether resistant bacterial strains are selected and whether they are still present in the faecal sample even a long time after therapy.     

Rifaximin for the treatment of irritable bowel syndrome

Introduction: Few therapeutic options are available for irritable bowel syndrome (IBS). Lubiprostone is approved by the FDA for IBS with constipation, and alosetron in IBS with diarrhea (IBS-D). It has been proposed that alterations in the bowel microflora may play a role in the pathophysiology of IBS, and that modulation of the microflora holds therapeutic potential. Rifaximin is a nonsystemic antibiotic that has shown efficacy in IBS.

Areas covered: This narrative review covers the treatment options available for IBS-D and focuses on rifaximin. Rifaximin pharmacodynamics, clinical pharmacology and results of clinical studies from proof of concept to the latest Phase III and retreatment studies in IBS are summarized. Challenges to rifaximin use, safety issues and regulatory data are also discussed.

Expert opinion: The evidence supports rifaximin as an emerging treatment for IBS. Strategies for appropriate patient selection need to be further developed, and continued efficacy of rifaximin over repeated treatment courses needs to be better characterized.     

小剂量阿米替林治疗腹泻型肠易激综合征临床疗效观察

目的探讨小剂量阿米替林对腹泻型肠易激综合征的疗效和耐受性。方法入选64例患者随机分为治疗组和对照组,治疗组每晚给予阿米替林12.5mg,安慰剂组每晚给予维生素C50mg,治疗6周后评价疗效及药物不良反应。结果64例患者全部完成治疗。治疗组症状全部都有改善,症状平均分从2.9分降为0.8分,与治疗前比较差异有统计学意义（P〈0.05）,总有效率为71.9%,与对照组比较差异有统计学意义（P〈0.05）,2组不良反应发生率差异无统计学意义（P〉0.05）。结论小剂量阿米替林治疗腹泻型肠易激综合征有效,患者耐受性好。     

思密达与美常安对腹泻型肠易激综合征的治疗效果

目的：观察思密达与美常安联合应用对腹泻型肠易激综合征（IBS）的治疗效果。方法：60例腹泻型1BS患者随机分为三组：联合用药组21例同时服思密达3g，tid及美常安胶囊500mg，tid，另两组分别服思密达（18例）或美常安（21例），剂量同前。记录治疗前后患者的症状、大便次数、大便性状。结果：联合用药组在服药d7时症状总评分已比治疗前下降78．1％，每日大便次数、大便性状评分已接近正常，与思密达组或美常安组比较，差异有统计学意义（P〈0．05），未观察到联合用药有明显的不良反应。结论：联合应用作用机制不同的思密达与美常安能迅速、安全地缓解腹泻型IBS的病情。     

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.     

Current and future pharmacological treatments for diarrhea-predominant irritable bowel syndrome

Introduction: Diarrhea-predominant irritable bowel syndrome (IBS-D) affects about one-third of patients with IBS, which is observed in about 12% of people across five continents. The ultimate goal in this field is to identify the underlying cause of symptoms in order to individualize education of the patient, and to provide optimal treatment of this highly prevalent condition.

Areas covered: This review addresses the pharmacological treatments for IBS-D under three categories: drugs for IBS-D (i.e., the 5-HT₃ antagonist, alosetron); drugs approved for other indications that are used in IBS-D (e.g., opioid agonists; other 5-HT₃ antagonists; serotonergic psychoactive agents; bile acid binders; 5-ASA compounds; probiotics and non-absorbable antibiotics); as well as development of drugs that are likely to impact the management of IBS-D in the future (e.g., drug absorbents; TPH₁ inhibitors; mast cell stabilizers; centrally acting benzodiazepines). The final section addresses key findings: regulatory roadblocks; weaknesses in the current research in this field so far and opportunities to address unmet needs including restoration of normal intestinal barrier function or permeability, and suppression within the intestines of local immune activation that is thought to trigger abnormal motor, sensory and secretory functions in IBS-D.

Expert opinion: While symptomatic treatment of diarrhea is effective, there is a need for new treatments for the IBS-D complex. Greater understanding of the mechanisms in IBS-D has led to promising approaches to develop more efficacious therapies.     

洁白胶囊联合阿米替林治疗腹肠易激综合征的临床研究

目的 观察洁白胶囊（抗胃肠功能紊乱药）联合阿米替林治疗腹泻型肠易激综合征（D-IBS）的疗效。方法 143例D-IBS患者随机分成3组，常规治疗组（48例）：每次VI服洁白胶囊0．8g，每天3次；联合治疗组（49例）：常规治疗外，睡前加用阿米替林，第1周，每天12．5mg；第2～4周，每天25mg；对照组（46例）：服用淀粉片每次1片，每天3次，饭后服用。4周为一疗程。结果 治疗1，2，4周后，常规治疗组有效率分别为60．4％，73．9％，77．8％；联合治疗组分别为65．3％，82．6％，93．2％，均明显高于安慰剂组（P〈0．01）；而联合组明显高于常规组（P〈0．05）。结论 洁白胶囊对D-IBS有较好疗效，阿米替林能明显增加洁白胶囊的治疗效果，且病人耐受性较好。     

乌灵胶囊治疗伴有抑郁症状的腹泻型肠易激综合征的对照研究

目的探讨乌灵胶囊治疗伴抑郁症状的腹泻型肠易激综合征（D-IBS）患者的临床疗效及安全性。方法按罗马标准Ⅲ选择60例D-IBS患者随机分为2组，研究组30例给予乌灵胶囊和培菲康，对照组30例给予培菲康；疗程8周。应用IBS症状变化及抑郁自评量表（SDS）于治疗前及治疗后进行疗效评定。结果治疗结束时，研究组中显效率、总有效率分别为59．3％和92.6％，对照组分别为30．8％和69.2％，有显著性差异。两组内治疗前与治疗后SDS积分均有显著性差异；治疗后第2、4、8周末研究组SDS积分与对照组相比有显著性差异。结论乌灵胶囊联用培菲康能快速缓解D-IBS的临床症状、改善抑郁症状，安全性好。     

Epidemiology,pathogenesis and treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a very common functional disorder of the gastrointestinal (GI) tract that is associated with significant healthcare costs and disability. Despite this, our understanding of this syndrome is yet limited and our treatment methods only modestly effective. The aim of this article is to review the epidemiology and pathophysiology of IBS and subsequently discuss the various treatment methods available, including current, novel and potential future therapies.     

肠易激综合征与抑郁症关系研究

近年来,生物-心理-社会医学模式倍受医学界关注,关于肠易激综合征与抑郁的关系研究越来越多,本文阐述伴抑郁障碍肠易激综合征患者特点,抑郁影响肠易激综合征症状的可能机制,对抗抑郁药物治疗肠易激综合征作用可能机理作一综述。     

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.     

微生态制剂在肠易激综合征中的临床应用及评价

肠易激综合征(IBS)是一组较为常见的、病因及发病机制未明的临床综合征,目前尚无特异性药物能用于缓解IBS患者的各种症状.近年来肠道菌群失调与IBS的关系,以及微生态制剂在IBS治疗中的应用逐渐引起人们的关注,本文简要综述微生态制剂与IBS的研究现状.     

腹泻型肠易激综合征及功能性腹泻的阶梯治疗回顾性分析

目的对腹泻型肠易激综合征（diarrhea-predominant irritable bowel syndrome, D-IBS）和功能性腹泻的腹泻情况进行程度分级,并按分级程度进行阶梯治疗,观察疗效。方法选取2008年6月~2013年11月本院门诊和住院患者中D-IBS和功能性腹泻病例195例,随机分为治疗组（99例）与对照组（96例）,按腹泻程度分为轻、中、重三度,治疗组进行四段阶梯式治疗,对照组仅予以止泻药蒙脱石散、洛哌丁胺,并视有无上消化道功能障碍予以伊托必利等,且不加用抗抑郁剂。所有病例至少随访半年。结果阶梯式治疗效果明显优于单用药物治疗者,两组比较治疗效果差异有统计学意义（P〈0.05）。结论并非每位腹泻的患者都需止泻药物治疗,相当多患者只需治疗腹泻以外的症状,仅少部分严重患者需要止泻药物和较长疗程的抗焦虑/抑郁治疗。按疾病的严重程度进行分级治疗,按主要症状进行对症治疗是治疗本病的原则。     

曲美布汀治疗肠易激综合征的临床疗效

目的 :观察曲美布汀治疗肠易激综合征(IBS)的临床疗效。方法 :参照罗马Ⅱ标准 ,选择 60例IBS病人 ,随机分成治疗组和对照组 ,每组 30例。对照组男性 12例 ,女性 18例 ,年龄 (33±s 16)a。治疗组男性 13例 ,女性 17例 ,年龄 (31± 12 )a。 2组均给予谷维素 (2 0mg ,po ,tid)、维生素B1(2 0mg ,po ,tid)、维生素C (0 .2 g ,po ,tid)。治疗组加用曲美布汀 2 0 0mg ,po ,tid ,疗程 2wk。观察治疗前后IBS腹痛、腹泻、便秘、腹胀的情况。结果 :治疗组wk 1总有效率 67% ,wk 2总有效率 83%。wk 2腹痛缓解率 90 % ,腹泻缓解率 89% ,便秘缓解率77% ,腹胀缓解率 81%。无明显不良反应。结论 :曲美布汀是治疗IBS安全有效的药物     

复方谷氨酰胺联合三联活菌胶囊治疗腹泻型肠易激综合征的安全性和有效性分析

目的 探讨复方谷氨酰胺联合三联活菌胶囊治疗腹泻型肠易激综合征的安全性和有效性.方法 选取2012年3月～2013年7月海南省人民医院收治的188例腹泻型肠易激综合征患者,随机分为3组:复方谷氨酰胺联合三联活菌胶囊治疗组(A组,n=63)、单独使用复方谷氨酰胺治疗组(B组,n=62)、单独使用双歧三联活菌胶囊治疗组(C组,n=63),2周为1个疗程;治疗前后,观察患者的肠道症状,记录3组患者腹泻、腹痛和腹胀发生次数.所有患者均在服药14d后评价疗效和生活质量及安全性.结果 治疗前,A、B、C3组平均每天腹泻(3.7±0.3)、(3.9±0.7)、(4.0±0.2)次,治疗14 d后平均每天(1.0±0.8)、(2.9±0.6),(3.1±0.8)次,3组治疗前后相比,差异均有统计学意义(P＜0.0).治疗7d后和14 d后,A组腹泻次数明显少于B、C2组,差异均有统计学意义(P＜0.05).治疗14 d后,A、B、C3组的总有效率分别为96.8％、83.8％和79.3％,A组总有效率明显高于B、C2组(P＜0.05).在生活质量上,A组患者的生活质量评分最高,且A组患者生活质量提高患者所占比例显著高于B组和C组(P＜0.05).结论 复方谷氨酰胺联合三联活菌胶囊治疗腹泻型肠易激综合征效果明显,疗效确切.     

门诊护理干预对肠易激综合征的作用

目的探讨门诊护理干预对肠易激综合征的治疗效果的影响。方法应用随机、单盲的方法,将山东中医药大学第二附属医院2008年4月至2009年8月门诊就诊的112例肠易激综合征患者随机分为对照组与实验组,实验组给予一般治疗及门诊护理干预,对照组仅给予一般治疗,门诊随访4周,观察患者症状改善情况及肛门测压。结果临床总疗效比较中观察组总有效率为91．1％;对照组总有效为38例,总有效率为67．9％。χ2=9．247,P〈0．01。两组比较差异有统计学意义。两组直肠压力变化中观察组总有效率为83．9％;对照组总有效为31例,总有效率为44．6％。χ2=10．811,P〈0．01。两组比较差异有统计学意义。结论门诊护理干预明显改善肠易激综合征的预后,是一种良好的辅助治疗手段。     

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.     

Atypical antipsychotics as a possible treatment option for irritable bowel syndrome

Introduction: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder (FGID) that is characterised by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits. Although the pathophysiology of IBS is not fully understood, it is believed that psychiatric comorbidities are highly common in such patients. A variety of psychotropic medications are widely used in the treatment of IBS, particularly older antidepressants such as tricyclic antidepressants (TCAs).

Areas covered: With the advent of newer antidepressant classes with better safety and tolerability compared with TCAs, such as serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), clinicians now have more advanced treatment options for treating IBS. Additionally, some atypical antipsychotics (AAs) have recently received approval for treatment of major depressive disorder (MDD). Some AAs may have potentials based on their pharmacodynamic profile and proven benefit for mood symptoms, pain, anxiety and sleep disturbances. This article describes the potential rationale, clinical data and practical aspects involved in the use of AAs for patients with IBS.

Expert opinion: Atypical antipsychotics (AAs) may have a role in the treatment of irritable bowel syndrome (IBS) based on the currently available findings, although there is no clear evidence, and a number of clinical issues to be addressed in the use of AAs for the treatment of IBS.     

Tenapanor hydrochloride for the treatment of constipation-predominant irritable bowel syndrome

Introduction: Constipation-predominant irritable bowel syndrome (IBS-C) is a common functional gastrointestinal (GI) disorder characterized by recurrent abdominal pain and prolonged GI transit. The pathogenesis of IBS-C has still not been established; therefore, drugs currently in use in IBS-C act mainly symptomatically, whereas novel pharmacological targets are urgently needed. Tenapanor is a potent inhibitor of Na⁺/H⁺ exchanger 3 [NHE3], localized in the apical membrane of intestinal epithelial cells. NHE3 participates in the uptake of sodium ions and water from the intestinal lumen.

Areas covered: In this review, the authors discuss pharmacodynamics and pharmacokinetics of tenapanor, focusing on animal models and in vitro studies. They also summarize clinical trials on tenapanor’s safety and efficacy in view of its potential role in IBS-C therapy.

Expert opinion: Tenapanor possesses an excellent preclinical safety profile and, as of now, there are no serious concerns about its side effects. The non-systemic action of tenapanor constitutes a significant advantage, as it minimizes possible adverse effects or drug–drug interactions. However, Phase III clinical trials are still needed to confirm results obtained in earlier phases and optimize the dose–response for tenapanor, whereas limiting diarrhea, its major adverse effect.