Systematic review with meta-analysis: lubiprostone efficacy on the treatment of patients with constipation.

BACKGROUND: Lubiprostone is a type 2 chloride channel activator that has been shown to be efficacious and safe in the treatment for chronic constipation. OBJECTIVE: To systematically review randomized clinical trials (RCTs) assessing efficacy of lubiprostone for patients with chronic idiopathic constipation (CIC), irritable bowel syndrome with predominant constipation (IBS-C) and opioid-induced constipation (OIC). METHODS: Searches were conducted in PubMed, LILACS, Cochrane Collaboration Database, and Centre for Reviews and Dissemination. Lubiprostone RCTs reporting outcomes of spontaneous bowel movements (SBM) and abdominal pain or discomfort were deemed eligible. Meta-analysis was performed calculating risk ratios and 95% confidence intervals, using the Mantel-Haenszel method and random effects model. RESULTS: Searches yielded 109 records representing 93 non-duplicate publications, and 11 RCTs (978 CIC, 1,366 IBS-C, 1,300 OIC, total = 3,644) met inclusion criteria. Qualitative synthesis showed that for CIC patients, lubiprostone is superior to placebo in terms of SBM outcomes. Meta-analysis for CIC was feasible for full responder and SBM within 24h rates, indicating superiority of lubiprostone over placebo. For IBS-C, lubiprostone was significantly superior for all SBM outcomes in follow-ups ranging from 1 week-3 months. In terms of abdominal pain, lubiprostone provided significantly better symptoms relief, particularly after 1 month of treatment. For OIC, lubiprostone was more effective than placebo for both SBM and discomfort measures. CONCLUSION: Our findings demonstrated that lubiprostone is superior to placebo in terms of SBM frequency for CIC, IBS-C and OIC. In terms of abdominal symptoms, the most pronounced effect was seen for abdominal pain in IBS-C patients.

Systematic review with meta-analysis: lubiprostone efficacy on the treatment of patients with constipation / Revisão sistemática com metanálise: eficácia da lubiprostona no tratamento de pacientes com constipação

ABSTRACT BACKGROUND: Lubiprostone is a type 2 chloride channel activator that has been shown to be efficacious and safe in the treatment for chronic constipation. OBJECTIVE: To systematically review randomized clinical trials (RCTs) assessing efficacy of lubiprostone for patients with chronic idiopathic constipation (CIC), irritable bowel syndrome with predominant constipation (IBS-C) and opioid-induced constipation (OIC). METHODS: Searches were conducted in PubMed, LILACS, Cochrane Collaboration Database, and Centre for Reviews and Dissemination. Lubiprostone RCTs reporting outcomes of spontaneous bowel movements (SBM) and abdominal pain or discomfort were deemed eligible. Meta-analysis was performed calculating risk ratios and 95% confidence intervals, using the Mantel-Haenszel method and random effects model. RESULTS: Searches yielded 109 records representing 93 non-duplicate publications, and 11 RCTs (978 CIC, 1,366 IBS-C, 1,300 OIC, total = 3,644) met inclusion criteria. Qualitative synthesis showed that for CIC patients, lubiprostone is superior to placebo in terms of SBM outcomes. Meta-analysis for CIC was feasible for full responder and SBM within 24h rates, indicating superiority of lubiprostone over placebo. For IBS-C, lubiprostone was significantly superior for all SBM outcomes in follow-ups ranging from 1 week-3 months. In terms of abdominal pain, lubiprostone provided significantly better symptoms relief, particularly after 1 month of treatment. For OIC, lubiprostone was more effective than placebo for both SBM and discomfort measures. CONCLUSION: Our findings demonstrated that lubiprostone is superior to placebo in terms of SBM frequency for CIC, IBS-C and OIC. In terms of abdominal symptoms, the most pronounced effect was seen for abdominal pain in IBS-C patients.

RESUMO CONTEXTO: Lubiprostona é um ativador de canal de cloreto tipo 2 que tem se demonstrado eficaz e seguro no tratamento da constipação crônica. OBJETIVO: Revisar sistematicamente ensaios clínicos randomizados (ECRs) avaliando a eficácia da lubiprostona para pacientes com constipação idiopática crônica (CIC), síndrome do intestino irritável com constipação predominante (IBS-C) e constipação induzida por opioide (OIC). MÉTODOS: Buscas foram conduzidas no PubMed, LILACS, Cochrane Collaboration Database e Centre for Reviews and Dissemination. ECRs de lubiprostona relatando desfechos de movimentos intestinais espontâneos (SBM) e dor ou desconforto abdominal foram considerados elegíveis. Metanálise foi realizada calculando razão de riscos e intervalos de confiança de 95%, utilizando o método de Mantel-Haenszel e modelo de efeitos aleatórios. RESULTADOS: As buscas identificaram 109 registros representando 93 publicações não-duplicadas e 11 ECRs (978 pacientes de CIC, 1366 de IBS-C e 1300 OIC, total = 3644) preencheram os critérios de inclusão. Síntese qualitativa mostrou que, para pacientes com CIC, a lubiprostona foi superior ao placebo em termos de desfechos SBM. Metanálise para CIC foi possível para os desfechos de responder completo e taxa de SBM em 24 horas, indicando superioridade da lubiprostona sobre o placebo. Para IBS-C, lubiprostona foi significativamente superior para todos os desfechos de SBM em tempos de seguimento variando de 1 semana a 3 meses. Em termos de dor abdominal, lubiprostona proporciono alívio dos sintomas significativamente melhor, particularmente após 1 mês de tratamento. Para OIC, lubiprostona foi mais efetiva do que placebo tanto para medidas de SBM quando de desconforto abdominal. CONCLUSÃO: Nossos achados demonstraram que lubiprostona é superior ao placebo em termos de frequência de SBM para CIC, IBS-C e OIC. Em termos de sintomas abdominais, o efeito mais pronunciado foi visto para dor abdominal em pacientes com IBS-C.

Short Chain Fatty Acids Effect on Chloride Channel ClC-2 as a Possible Mechanism for Lubiprostone Intestinal Action.

Lubiprostone, a 20-carbon synthetic fatty acid used for the treatment of constipation, is thought to act through an action on Cl- channel ClC-2. Short chain fatty acids (SCFAs) are produced and absorbed in the distal intestine. We explore whether SCFAs affect ClC-2, re-examine a possible direct effect of lubiprostone on ClC-2, and use mice deficient in ClC-2 to stringently address the hypothesis that the epithelial effect of lubiprostone targets this anion channel. Patch-clamp whole cell recordings of ClC-2 expressed in mammalian cells are used to assay SCFA and lubiprostone effects. Using chamber measurements of ion current in mice deficient in ClC-2 or CFTR channels served to analyze the target of lubiprostone in the distal intestinal epithelium. Intracellular SCFAs had a dual action on ClC-2, partially inhibiting conduction but, importantly, facilitating the voltage activation of ClC-2. Intra- or extracellular lubiprostone had no effect on ClC-2 currents. Lubiprostone elicited a secretory current across colonic epithelia that was increased in mice deficient in ClC-2, consistent with the channel's proposed proabsorptive function, but absent from those deficient in CFTR. Whilst SCFAs might exert a physiological effect on ClC-2 as part of their known proabsorptive effect, ClC-2 plays no part in the lubiprostone intestinal effect that appears mediated by CFTR activation.

Management of constipation in Parkinson's disease.

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.

[Pharmacological treatment of the irritable bowel syndrome: a technical review]. / Tratamiento farmacológico del síndrome de intestino irritable: revisión técnica.

INTRODUCTION: The goal of a comprehensive treatment in irritable bowel syndrome (IBS) patients should be the improvement of symptoms and improve the quality of life. AIM: To review the drugs recommended in IBS, their mechanisms of action, side effects, risks and benefits, contraindications, availability in our country and the evidence supporting their use. MATERIAL AND METHODS: A technical and narrative review which evaluated the articles published in national and world literature regarding the pharmacological treatment of IBS was performed. PubMed and IMBIOMED electronic databases were searched (until September 2009) using all descriptors regarding IBS and drug therapy. RESULTS: There is enough clinical evidence to recommend the use of antispasmodics (alone orin combination) and tricyclic antidepressants for pain treatment in IBS. Laxatives are useful in the management of chronic constipation, but there is little evidence in the management of IBS. Although, antiflatulents and antidiarrheals are widely used there is little information supporting its use. The use of a nonabsorbable antibiotic (rifaximin) is effective in a subgroup of IBS patients. Serotoninergics drugs have proven effective in relieving symptoms of IBS; however, these drugs require caution in their use. There are studies have shown that probiotics improve some symptoms of IBS. CONCLUSIONS: There are many effective treatment options in the symptomatic management of IBS. The choice of treatment should be based on the predominant symptoms of each patient.