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BACKGROUND & AIMS: Functional constipation is the most common of the disorders of gut-brain interaction, affecting approximately 12% of the world population. Although classically considered a chronic condition, many individuals experience shorter yet repetitive bouts of constipation representing a different clinical entity. There has been increased interest in this latter disorder, which has recently been classified as occasional constipation. This Rome Foundation working group document reflects the consensus of an international team of specialists who summarized currently available research to provide a working definition of and treatment algorithm for occasional constipation. The recommendations herein are based on current evidence, accounting for gaps in the literature as well as international variance in definitions and health seeking behaviors for constipation. METHODS: The committee members reviewed the scientific literature, focusing specifically on occasional constipation, with the understanding that as a new entity, a paucity of data would be available. We used Rome IV research and clinical definitions to establish the framework for our definition of occasional constipation. Where possible, treatment recommendations were determined on the basis of the earliest extractable data from functional constipation studies, focusing on positive results within the first 2 weeks of treatment. We used the Delphi method to create consensus with 100% agreement between the authors. RESULTS: An evidence-based review of the literature resulted in the definition of occasional constipation as follows: "individuals who experience the presence of at least 1 functional constipation symptom, in the absence of alarm signs or symptoms, occurring at irregular and infrequent intervals, which is bothersome enough to induce a patient to seek medical management." Medical management whether seeking medical care or self-treatment was left to the individual's discretion, and we did not include time anchors because these thresholds require further investigation. Polyethylene glycol and stimulant laxatives are recommended as first-line interventions, whereas magnesium-containing compounds are suggested in individuals failing to respond to these therapies. There are insufficient data to make recommendations for using fiber or stool softeners. Prescription laxatives should be reserved for individuals with chronic constipation. CONCLUSIONS: Occasional constipation is a unique clinical entity characterized by infrequent but recurrent symptoms. Data are limited because consensus definitions have been lacking. Establishing a standardized definition and therapeutic recommendations provides a framework for future studies focusing on epidemiologic and symptoms-based outcomes. Further studies are needed to confirm and refine these recommendations.
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Constipação Intestinal , Laxantes , Humanos , Laxantes/uso terapêutico , Consenso , Cidade de Roma , Constipação Intestinal/terapia , Constipação Intestinal/tratamento farmacológico , Polietilenoglicóis/uso terapêuticoRESUMO
BACKGROUND: Various dietary strategies for managing irritable bowel syndrome (IBS) target mechanisms such as brain-gut interactions, osmotic actions, microbial gas production, and local immune activity. These pathophysiological mechanisms are diverse, making it unclear which foods trigger IBS symptoms for a substantial proportion of patients. AIM: To identify associations between foods and gastrointestinal symptoms. METHODS: From the mySymptoms smartphone app, we collected anonymized diaries of food intake and symptoms (abdominal pain, diarrhea, bloating, and gas). We selected diaries that were at least 3 weeks long. The diaries were analyzed for food-symptom associations using a proprietary algorithm. As the participants were anonymous, we conducted an app-wide user survey to identify IBS diagnoses according to Rome IV criteria. RESULTS: A total of 9,710 food symptom diaries that met the quality criteria were collected. Of the survey respondents, 70% had IBS according to Rome IV criteria. Generally, strong associations existed for caffeinated coffee (diarrhea, 1-2 h postprandial), alcoholic beverages (multiple symptoms, 4-72 h postprandial), and artificial sweeteners (multiple symptoms, 24-72 h postprandial). Histamine-rich food intake was associated with abdominal pain and diarrhea. Some associations are in line with existing literature, whilst the absence of an enriched FODMAP-symptom association contrasts with current knowledge. CONCLUSIONS: Coffee, alcohol, and artificial sweeteners were associated with GI symptoms in this large IBS-predominant sample. Symptom onset is often within 2 h postprandial, but some foods were associated with a delayed response, possibly an important consideration in implementing dietary recommendations. Clinical trials must test the causality of the demonstrated food-symptom associations.
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Dor Abdominal , Café , Síndrome do Intestino Irritável , Edulcorantes , Humanos , Café/efeitos adversos , Síndrome do Intestino Irritável/diagnóstico , Feminino , Masculino , Adulto , Edulcorantes/efeitos adversos , Dor Abdominal/etiologia , Pessoa de Meia-Idade , Diarreia/etiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Aplicativos Móveis , Etanol/efeitos adversos , Registros de DietaRESUMO
Inclusion in nasogastric tube feeds (NGTF) of acid-sensitive, seaweed-derived alginate, expected to form a reversible gel in the stomach, may create a more normal intragastric state and modified gastrointestinal responses. This may ameliorate NGTF-associated risk of diarrhoea, upper gastrointestinal symptoms and appetite suppression. In a randomised, crossover, comparison study, undertaken in twelve healthy males, an alginate-containing feed (F + ALG) or one that was alginate-free (F-ALG) (300 ml) was given over 1 h with a 7-14-d washout period between treatments. Baseline and for 4-h post-feed initiation, MRI measurements were made to establish small bowel water content (SBWC), gastric contents volume (GCV) and appearance, and superior mesenteric artery blood flux. Blood glucose and gut peptides were measured. Subjective appetite and upper gastrointestinal symptoms scores were obtained. Ad libitum pasta consumption 3-h post-feeding was measured. F + ALG exhibited a gastric appearance consistent with gelling surrounded by a freely mobile water halo. Significant main effects of feed were seen for SBWC (P = 0·03) and peptide YY (PYY) (P = 0·004) which were attributed to generally higher values for SBWC with F + ALG (max difference between adjusted means 72 ml at 210 min) and generally lower values for PYY with F + ALG. GCV showed a faster reduction with F + ALG, less between-participant variation and a feed-by-time interaction (P = 0·04). Feed-by-time interactions were also seen with glucagon-like-peptide 1 (GLP-1) (P = 0·02) and glucose-dependent insulinotropic polypeptide (GIP) (P = 0·002), both showing a blunted response with F + ALG. Apparent intragastric gelling with F + ALG and subsequent differences in gastrointestinal and endocrine responses have been demonstrated between an alginate-containing and alginate-free feed.
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Alginatos , Gastroenteropatias , Masculino , Humanos , Alginatos/química , Alginatos/farmacologia , Nutrição Enteral , Intestino Delgado , Polipeptídeo Inibidor Gástrico , Apetite , Imageamento por Ressonância Magnética , Peptídeo YY , Água , Estudos Cross-Over , InsulinaRESUMO
Functional dyspepsia (FD) is a common disorder of gut-brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research.
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Dispepsia , Dispepsia/diagnóstico , Dispepsia/terapia , Gastroenterologia , Humanos , Sociedades Médicas , Reino UnidoRESUMO
Functional abdominal cramping pain (FACP) is a common complaint, which may present either on its own or in association with a functional gastrointestinal disorder. It is likely caused by a variety of, probably partly unknown, etiologies. Effective management of FACP can be challenging owing to the lack of usable diagnostic tools and the availability of a diverse range of treatment approaches. Practical guidance for their selection and use is limited. The objective of this article is to present a working definition of FACP based on expert consensus, and to propose practical strategies for the diagnosis and management of this condition for physicians, pharmacists, and patients. A panel of experts on functional gastrointestinal disorders was convened to participate in workshop activities aimed at defining FACP and agreeing upon a recommended sequence of diagnostic criteria and management recommendations. The key principles forming the foundation of the definition of FACP and suggested management algorithms include the primacy of cramping pain as the distinguishing symptom; the importance of recognizing and acting upon alarm signals of potential structural disease; the recognition of known causes that might be addressed through lifestyle adjustment; and the central role of antispasmodics in the treatment of FACP. The proposed algorithm is intended to assist physicians in reaching a meaningful diagnostic endpoint based on patient-reported symptoms of FACP. We also discuss how this algorithm may be adapted for use by pharmacists and patients.
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Gastroenteropatias , Parassimpatolíticos , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/terapia , Consenso , HumanosRESUMO
Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.
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Terapia Cognitivo-Comportamental , Constipação Intestinal/tratamento farmacológico , Diarreia/tratamento farmacológico , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia , Pesquisa Biomédica , Comunicação , Constipação Intestinal/etiologia , Diarreia/etiologia , Dieta , Desenvolvimento de Medicamentos , Humanos , Hipnose , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/fisiopatologia , Educação de Pacientes como Assunto , Relações Médico-Paciente , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Antagonistas da Serotonina/uso terapêutico , Reino UnidoRESUMO
Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. The pathophysiology of irritable bowel syndrome is incompletely understood, but it is well established that there is disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and altered CNS processing. Other less reproducible mechanisms might include genetic associations, alterations in gastrointestinal microbiota, and disturbances in mucosal and immune function. In most people, diagnosis can be made on the basis of clinical history with limited and judicious use of investigations, unless alarm symptoms such as weight loss or rectal bleeding are present, or there is a family history of inflammatory bowel disease or coeliac disease. Once the diagnosis is made, an empathetic approach is key and can improve quality of life and symptoms, and reduce health-care expenditure. The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development.
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Dor Abdominal/etiologia , Encéfalo/fisiopatologia , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Fibras na Dieta/administração & dosagem , Fármacos Gastrointestinais/administração & dosagem , Gastroenteropatias/fisiopatologia , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/terapia , Qualidade de VidaRESUMO
BACKGROUND & AIMS: The existence of postinfection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized, and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based on findings reported in the literature and clinical experience. METHODS: The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways, and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members. RESULTS: PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or before acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There are no evidence-based, effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms. CONCLUSIONS: Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based on team consensus. We also propose areas for future investigation.
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Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/terapia , Gastroenterite/diagnóstico , Gastroenterite/terapia , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia , Algoritmos , Animais , Tomada de Decisão Clínica , Doenças Transmissíveis/epidemiologia , Consenso , Técnica Delphi , Gastroenterite/epidemiologia , Humanos , Síndrome do Intestino Irritável/etiologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Fatores de RiscoRESUMO
Food-drug interaction is an infrequently considered aspect in clinical practice. Usually, drugs are taken together with meals and what follows may adversely affect pharmacokinetic and pharmacodynamic properties, and hence, the therapeutic effects. In this study, a computational protocol was proposed to explain the different assimilations of two µ-receptors agonists, eluxadoline and loperamide, with a peculiar pharmacokinetic profile. Compared to loperamide, eluxadoline is absorbed less after the intake of a fatty meal, and the LogP values do not explain this event. Firstly, keeping in mind the different pH in the intestinal tract, the protonation states of both compounds were calculated. Then, all structures were subjected to a conformational search by using MonteCarlo and Molecular Dynamics methods, with solvation terms mimicking the water and weak polar solvent (octanol). Both computational results showed that eluxadoline has less conformational freedom in octanol, unlike loperamide, which exhibits constant behavior in both solvents. Therefore, we hypothesize that fatty meal causes the "closure" of the eluxadoline molecule to prevent the exposure of the polar groups and their interaction with water, necessary for the drug absorption. Based on our results, this work could be a reasonable "case study", useful for future investigation of the drug pharmacokinetic profile.
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Dieta Hiperlipídica , Gorduras na Dieta , Gorduras/química , Interações Alimento-Droga , Imidazóis/química , Refeições , Fenilalanina/análogos & derivados , Humanos , Imidazóis/farmacologia , Modelos Moleculares , Conformação Molecular , Método de Monte Carlo , Fenilalanina/química , Fenilalanina/farmacologia , Eletricidade Estática , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery. DESIGN: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous. RESULTS: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett's oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis. CONCLUSION: With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.
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Refluxo Gastroesofágico/cirurgia , Seleção de Pacientes , Adulto , Atitude do Pessoal de Saúde , Consenso , Técnica Delphi , Endoscopia , Monitoramento do pH Esofágico , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/patologia , Humanos , Manometria , Guias de Prática Clínica como Assunto , Padrões de Prática MédicaRESUMO
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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Consenso , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Diagnóstico Diferencial , Gastroenteropatias/etiologia , HumanosRESUMO
OBJECTIVES: Only a few studies have applied high-resolution manometry (HRM) to the study of colonic motility in adults and none of them have concurrently evaluated colonic and anal motor activity. The aim of the study was to evaluate colonic and anal motor activity by means of HRM in healthy subjects. As the present study revealed the presence of a new colonic motor pattern (pan-colonic pressurizations) in healthy subjects, three additional studies were conducted: the first and the second to exclude that this motor event results from an artifact due to abdominal wall contraction and to confirm its modulation by cholinergic stimulation, and the third, as pilot study, to test the hypothesis that this colonic pattern is defective in patients with chronic constipation refractory to current pharmacological treatments. METHODS: In both volunteers and patients the HRM catheter was advanced proximally during colonoscopy. RESULTS: In all subjects, pressure increases of 15±3 mm Hg and 24±4 s simultaneously occurring in all colonic sensors (pan-colonic pressurizations) and associated with anal sphincter relaxation were identified. Subjects had 85±38 pan-colonic pressurizations, which increased significantly during meal (P=0.007) and decreased afterward (P=0.01), and were correlated with feelings of and desire to evacuate gas. The mean number of propagating sequences was 47±39, and only retrograde increased significantly postprandially (P=0.01). Pan-colonic pressurizations differed from strain artifacts and significantly increased after prostigmine. In patients pan-colonic pressurizations were significantly reduced as compared with volunteers. CONCLUSIONS: Pan-colonic pressurizations associated with relaxations of the anal sphincter represent a new colonic motor pattern that seems to be defective in patients with treatment-refractory chronic constipation and may have a role in the transport of colonic gas and in the facilitation of the propagating sequence-induced colonic transport.
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Canal Anal/fisiologia , Colo/fisiologia , Constipação Intestinal/fisiopatologia , Trânsito Gastrointestinal/fisiologia , Manometria , Pressão , Parede Abdominal , Adulto , Canal Anal/efeitos dos fármacos , Canal Anal/fisiopatologia , Estudos de Casos e Controles , Inibidores da Colinesterase/farmacologia , Doença Crônica , Colo/efeitos dos fármacos , Colo/fisiopatologia , Eletromiografia , Feminino , Motilidade Gastrointestinal/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neostigmina/farmacologia , Projetos Piloto , Adulto JovemRESUMO
In the treatment of irritable bowel syndrome (IBS), loperamide seems efficacious for diarrhea and ispaghula for constipation, while musculotropic spasmolytics may relieve abdominal pain. Antidepressants were found to be efficacious for abdominal pain, but their tolerance may be problematic and the therapeutic effect varied largely between trials. While meta-analyses suggest efficacy of probiotics as a group, the quality of the trials is often suboptimal and there is large variability. Lubiprostone, a chloride channel activator, and linaclotide, a guanylyl cyclase-C agonist, showed favorable effects on multiple symptoms in IBS with constipation. For IBS with diarrhea (IBS-D), the 5-HT3 receptor antagonist ramosetron showed efficacy in men and women, but is currently only approved in Japan. A multicenter study with the anti-emetic 5-HT3 receptor antagonist ondansetron showed efficacy on stool pattern in IBS-D. The poorly absorbable antibiotic rifaximin and eluxadoline, a mu opioid receptor agonist and delta antagonist, both showed efficacy in phase III trials in IBS-D and were approved by the FDA. Eluxadoline was associated with increased occurrence of sphincter of Oddi spasm and biliary pancreatitis. The non-pharmacological treatment of IBS, with dietary interventions (mainly gluten elimination and low FODMAP (fructose, oligo-, di-, monosaccharides and polyols)) has received a lot of attention lately. While responder rates vary across studies, perhaps based on regional variations in dietary intake of FODMAPs, the dietary approach seems to have acquired recognition as a valid therapeutic alternative. Long-term studies and comparative studies with pharmacotherapy, as well as elucidation of the underlying mechanisms of action, are needed.
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Fármacos Gastrointestinais/uso terapêutico , Motilidade Gastrointestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/tratamento farmacológico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Adulto , Antibacterianos/uso terapêutico , Antieméticos/uso terapêutico , Benzimidazóis/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Diarreia/tratamento farmacológico , Diarreia/etiologia , Feminino , Humanos , Imidazóis/uso terapêutico , Síndrome do Intestino Irritável/complicações , Lubiprostona/uso terapêutico , Masculino , Pessoa de Meia-Idade , Peptídeos/uso terapêutico , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Probióticos/uso terapêutico , Rifamicinas/uso terapêutico , RifaximinaRESUMO
The classic symptoms of irritable bowel syndrome (IBS) are abdominal pain, bloating and some form of bowel dysfunction. The pain is typically colicky in nature and can occur at any site although most commonly it is on the left side. The abdomen feels flat in the morning and then gradually becomes more bloated as the day progresses reaching a peak by late afternoon or evening. It then subsides again over night. Traditionally IBS is divided into diarrhoea, constipation or alternating subtypes. IBS patients frequently complain of one or more non-colonic symptoms, these include constant lethargy, low backache, nausea, bladder symptoms suggestive of an irritable bladder, chest pain and dyspareunia in women. The traditional view that IBS is a largely psychological condition is no longer tenable. Rectal bleeding, a family history of malignancy and a short history in IBS should always be treated with suspicion. Both pain and bowel dysfunction are often made worse by eating. It is recommended that a coeliac screening test is undertaken to rule out this condition. Other routine tests should include inflammatory markers such as CRP or ESR. Calprotectin is a marker for leukocytes in the stools and detects gastrointestinal inflammation. A negative test almost certainly rules out inflammatory bowel disease, especially in conjunction with a normal CRP. Fermentable carbohydrates can have a detrimental effect on IBS and this has led to the introduction of the low FODMAP diet.
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Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/terapia , Atenção Primária à Saúde , Dieta , Fármacos Gastrointestinais , Humanos , Educação de Pacientes como AssuntoRESUMO
Introduction: Drotaverine, paracetamol, and peppermint oil are often prescribed for the treatment of gastrointestinal spasm and pain. This study aimed to evaluate the effect of these drugs alone and combined with the well-known antispasmodic hyoscine butylbromide on the human colon. Methods: Colon samples were obtained from macroscopically normal regions of 68 patients undergoing surgery and studied in muscle bath. Drotaverine, paracetamol, and peppermint oil were tested alone and in combination with hyoscine butylbromide on (1) spontaneous contractility induced by isometric stretch (in the presence of 1 µM tetrodotoxin) and (2) contractility induced by 10-5 M carbachol and after (3) electrical field stimulation-induced selective stimulation of excitatory (in the presence of 1 mM Nω-nitro-L-arginine and 10 µM MRS2179) and (4) inhibitory (under non-adrenergic, non-cholinergic conditions) pathways. (5) Drotaverine alone was also tested on cAMP-dependent pathway activated by forskolin. Results: Compared with the vehicle, drotaverine and paracetamol (10-9-10-5 M) did not modify spontaneous contractions, carbachol-induced contractions, and responses attributed to selective activation of excitatory pathways. The addition of hyoscine butylbromide (10-7-10-5 M), concentration-dependently reduced myogenic contractions and carbachol- and electrical field stimulation-induced contractile responses. The association of paracetamol (10-4 M) and hyoscine butylbromide (10-7-10-5 M) was not different from hyoscine butylbromide alone (10-7-10-5 M). At higher concentrations (10-3M-3*10-3 M), paracetamol decreased myogenic and carbachol-induced contractions. The adenylate cyclase activator, forskolin, concentration-dependently reduced contractility, leading to smooth muscle relaxation. The effect of forskolin 10-7 M was concentration-dependently enhanced by drotaverine (10-6M-10-5M). Discussion: Peppermint oil reduced myogenic activity and carbachol- and electrical field stimulation-induced contractions. The association of hyoscine butylbromide and peppermint oil was synergistic since the interaction index measured with the isobologram was lower than 1. No effect was seen on the neural-mediated inhibitory responses with any of the drugs studied although peppermint oil reduced the subsequent off-contraction. Drotaverine and hyoscine butylbromide have a complementary effect on human colon motility as one stimulates the cAMP inhibitory pathway and the other inhibits the excitatory pathway. Peppermint oil is synergic with hyoscine butylbromide suggesting that a combination therapy may be more effective in treating patients. In contrast, at therapeutic concentrations, paracetamol does not modify colonic contractility, suggesting that the association of paracetamol and hyoscine butylbromide has independent analgesic and antispasmodic properties.
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INTRODUCTION: Hyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways. METHODS: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators. RESULTS: In the presence of tetrodotoxin (TTX), HBB and atropine 1 µM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses. CONCLUSIONS: This study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin.
Assuntos
Brometo de Butilescopolamônio , Colo , Contração Muscular , Humanos , Brometo de Butilescopolamônio/farmacologia , Colo/efeitos dos fármacos , Colo/fisiologia , Masculino , Feminino , Contração Muscular/efeitos dos fármacos , Pessoa de Meia-Idade , Idoso , Estimulação Elétrica , Adulto , Carbacol/farmacologia , Parassimpatolíticos/farmacologia , Idoso de 80 Anos ou mais , Técnicas In VitroRESUMO
Transition services-programs that support adolescents and young adults (AYAs) as they move from a child-centered to a more autonomous, adult-orientated healthcare system-have been associated with improved short- and long-term healthcare outcomes. Unfortunately, there is a paucity of evidence exploring transition services within the neurogastroenterology and motility (NGM) field. The overall aim of this article, endorsed by the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility, is to promote a discussion about the role of transition services for patients with NGM disorders. The AYAs addressed herein are those who have: (a) a ROME positive disorder of gut-brain interaction (DGBI), (b) a primary or secondary motility disorder (including those with motility disorders that have been surgically managed), or (c) an artificial feeding requirement (parenteral or enteral tube feeding) to manage malnutrition secondary to categories (a) or (b). The issues explored in this position paper include the specific physical and psychological healthcare needs of patients with NGM disorders; key healthcare professionals who should form part of a secondary care NGM transition service; the triadic relationship between healthcare professionals, caregivers, and patients; approaches to selecting patients who may benefit most from transition care; methods to assess transition readiness; and strategies with which to facilitate transfer of care between healthcare professionals. Key areas for future research are also addressed, including the construction of NGM-specific transition readiness questionnaires, tools to assess post-transfer healthcare outcomes, and educational programs to train healthcare professionals about transition care in NGM.
RESUMO
BACKGROUND: Hyoscine butylbromide (HBB) has been available for use as an antispasmodic since 1951 and is indicated for the treatment of abdominal pain associated with cramps. A previous review in 2007 summarized the evidence on the mode of action of HBB in vitro and in vivo in both animal and human studies. However, since then, novel publications have appeared within the literature and also our knowledge of what represents normal motility in humans has evolved. PURPOSE: This review is the result of the collaboration between a basic scientist and clinicians with the aim of providing an updated overview of the mechanisms of action of HBB and its clinical efficacy to guide not only use in clinical practice, but also future research.