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1.
Clin Gastroenterol Hepatol ; 21(4): 1082-1090, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35341952

RESUMO

BACKGROUND & AIMS: Rectal evacuation disorders are common among constipated patients. We aimed to evaluate the accuracy of an investigational point-of-care test (rectal expulsion device [RED]) to predict outcomes with community-based pelvic floor physical therapy. METHODS: We enrolled patients meeting Rome IV criteria for functional constipation failing fiber/laxatives for more than 2 weeks. RED was inserted and self-inflated, and then time-to-expel was measured in a left lateral position. All patients underwent empiric community-based pelvic floor physical therapy in routine care with outcomes measured at 12 weeks. The primary end point was global clinical response (Patient Assessment of Constipation Symptoms score reduction, >0.75 vs baseline). Secondary end points included improvement in health-related quality-of-life (Patient Assessment of Constipation Quality of Life score reduction, >1.0) and complete spontaneous bowel movement frequency (Food and Drug Administration complete spontaneous bowel movement responder definition). RESULTS: Thirty-nine patients enrolled in a feasibility phase to develop the use-case protocol. Sixty patients enrolled in a blinded validation phase; 52 patients (mean, 46.9 y; 94.2% women) were included in the intention-to-treat analysis. In the left lateral position, RED predicted global clinical response (generalized area under the curve [gAUC], 0.67; 95% CI, 0.58-0.76]), health-related quality-of-life response (gAUC, 0.67; 95% CI, 0.58-0.77; P < .001), and complete spontaneous bowel movement response (gAUC, 0.63; 95% CI, 0.57-0.71; P < .001). As a screening test, a normal RED effectively rules out evacuation disorders (expected clinical response, 8.9%; P = .042). Abnormal RED in the left lateral position (defined as expulsion within 5 seconds or >120 seconds) predicted 48.9% clinical response to physical therapy. A seated maneuver enhanced the likelihood of clinical response (71.1% response with seated RED retained >13 seconds) but likely is unnecessary in most settings. CONCLUSIONS: RED offers an opportunity to disrupt the paradigm by offering a personalized approach to managing chronic constipation in the community (Clinicaltrials.gov: NCT04159350).


Assuntos
Diafragma da Pelve , Doenças Retais , Humanos , Feminino , Masculino , Qualidade de Vida , Constipação Intestinal/diagnóstico , Constipação Intestinal/terapia , Defecação/fisiologia , Resultado do Tratamento , Modalidades de Fisioterapia
2.
Pediatr Surg Int ; 39(1): 229, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37428259

RESUMO

PURPOSE: This study aimed to analyze our radiologically supervised bowel management program (RS-BMP) outcomes in patients with chronic idiopathic constipation (CIC). METHODS: A retrospective study was conducted. We included all patients with CIC who participated in our RS-BMP at Children´s Hospital Colorado from July 2016 to October 2022. RESULTS: Eighty patients were included. The average time with constipation was 5.6 years. Before our RS-BMP, 95% had received non-radiologically supervised treatments, and 71% had attempted two or more treatments. Overall, 90% had tried Polyethylene Glycol and 43% Senna. Nine patients had a history of Botox injections. Five underwent anterograde continence procedure, and one a sigmoidectomy. Behavioral disorders (BD) were found in 23%. At the end of the RS-BMP, 96% of patients had successful outcomes, 73% were on Senna, and 27% were on enemas. Megarectum was detected in 93% of patients with successful outcomes and 100% with unsuccessful outcomes (p = 0.210). Of the patients with BD, 89% had successful outcomes, and 11% had unsuccessful. CONCLUSION: Our RS-BMP has been proven to be effective in treating CIC. The radiologically supervised use of Senna and enemas was the appropriate treatment in 96% of the patients. BD and megarectum were associated with unsuccessful outcomes.


Assuntos
Constipação Intestinal , Megacolo , Criança , Humanos , Estudos Retrospectivos , Constipação Intestinal/diagnóstico por imagem , Constipação Intestinal/terapia , Senosídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Enema , Colo Sigmoide , Resultado do Tratamento
3.
Curr Gastroenterol Rep ; 24(10): 115-126, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35943661

RESUMO

PURPOSE OF REVIEW: Colonic motility disorders may be influenced by the gut microbiota, which plays a role in modulating sensory and motor function. However, existing data are inconsistent, possibly due to complex disease pathophysiology, fluctuation in symptoms, and difficulty characterizing high-resolution taxonomic composition and function of the gut microbiome. RECENT FINDINGS: Increasingly, human studies have reported associations between gut microbiome features and colonic motility disorders, such as irritable bowel syndrome and constipation. Several microbial metabolites have been identified as regulators of colonic motility in animal models. Modulation of the gut microbiota via dietary intervention, probiotics, and fecal microbiota transplant is a promising avenue for treatment for these diseases. An integration of longitudinal multi-omics data will facilitate further understanding of the causal effects of dysbiosis on disease. Further understanding of the microbiome-driven mechanisms underlying colonic motility disorders may be leveraged to develop personalized, microbiota-based approaches for disease prevention and treatment.


Assuntos
Gastroenterologistas , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Animais , Humanos , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/terapia , Constipação Intestinal , Diarreia , Metagenoma
4.
Gut ; 67(8): 1543-1552, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29563144

RESUMO

Functional gastrointestinal disorders (FGIDs) and IBDs are two of the most prevalent disorders of the GI tract and consume a significant proportion of healthcare resources. Recent studies have shown that membrane-bound guanylate cyclase-C (GC-C) receptors lining the GI tract may serve as novel therapeutic targets in the treatment of FGIDs and IBDs. GC-C receptor activation by its endogenous paracrine hormones uroguanylin and guanylin, and the resulting intracellular production of its downstream effector cyclic GMP, occurs in a pH-dependent manner and modulates key physiological functions. These include fluid and electrolyte homeostasis, maintenance of the intestinal barrier, anti-inflammatory activity and regulation of epithelial regeneration. Studies of the GC-C paracrine signalling axis have revealed the therapeutic potential of these receptors in treating GI disorders, including chronic idiopathic constipation and irritable bowel syndrome-constipation. This review focuses on the evolving understanding of GC-C function in health and disease, and strategies for translating these principles into new treatments for FGIDs and IBDs.


Assuntos
Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Receptores Acoplados a Guanilato Ciclase/fisiologia , Gastroenteropatias/diagnóstico , Humanos
5.
Dig Dis Sci ; 62(12): 3568-3578, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28849329

RESUMO

BACKGROUND: Lubiprostone is a ClC-2 chloride channel activator approved for the treatment of chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC) in adults and irritable bowel syndrome with constipation (IBS-C) in women. Lubiprostone is generally well tolerated, with nausea being the most common adverse event. AIMS: To characterize nausea with lubiprostone using pooled results from clinical studies in patients with CIC, OIC, or IBS-C. METHODS: Data from three 3- and 4-week placebo-controlled studies and three long-term open-label studies were pooled for the CIC analysis. The OIC and IBS-C analyses each used pooled data from three 12-week placebo-controlled studies and one 36-week open-label extension study. RESULTS: The populations included the following numbers of patients: CIC, 316 (placebo) and 1113 (lubiprostone 24 mcg twice daily [BID]); OIC, 652 (placebo) and 889 (lubiprostone 24 mcg BID); and IBS-C, 435 (placebo) and 1011 (lubiprostone 8 mcg BID). The incidence of nausea in lubiprostone-treated patients ranged from 11.4 to 31.1%, with the highest incidence in patients with CIC. Among patients with any nausea, most reported only mild or moderate severity (96.5-99.1% across indications) and only one event (83.6-88.7%); most events occurred within the first 5 days of treatment. CONCLUSIONS: Nausea was the most common adverse event following the treatment with lubiprostone. Event rates varied by indication and dose, and the majority of nausea adverse events were mild to moderate in severity. Nausea events predominantly occurred early in the treatment period in all of the pooled study populations.


Assuntos
Agonistas dos Canais de Cloreto/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Lubiprostona/efeitos adversos , Náusea/induzido quimicamente , Humanos
6.
Expert Opin Pharmacother ; 25(10): 1281-1290, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39058326

RESUMO

INTRODUCTION: Chronic idiopathic constipation (CIC) is characterized by infrequent bowel movements and hard stools lasting for at least three months or longer. This disease affects 8-12% of the US population and 10-17% of the world population. Treatment and management involve identifying the primary cause, changing dietary habits, and adequate physical activity. Linaclotide is a guanylate cyclase-agonist acting locally in the luminal surface of the intestinal enterocyte leading to a signal transduction cascade, activation of the cystic fibrosis transmembrane conductance regulator (CFTR), thus increasing secretion of chloride and bicarbonate into the intestinal lumen with eventual increased intestinal fluid and faster transit time. AREAS COVERED: We reviewed multiple studies and did a thorough literature review on CIC including its pathophysiology. Through this literature review, we were able to discuss and give the context and rationale for drug regimens indicated for CIC. EXPERT OPINION: The era we live in right now is akin to nutrient-rich and fertilized soil as knowledge and resources are abundant. The opportunities and potential are endless. Constipation being more extensively studied, our understanding of medications and diseases broadens, leading to novel medications being discovered. Linaclotide is a pioneer in this aspect and can pave the way for future generations.


Assuntos
Constipação Intestinal , Agonistas da Guanilil Ciclase C , Peptídeos , Humanos , Constipação Intestinal/tratamento farmacológico , Doença Crônica , Peptídeos/uso terapêutico , Agonistas da Guanilil Ciclase C/uso terapêutico , Animais , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/agonistas , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-38317751

RESUMO

Background: Multiple pharmacological interventions and modalities are available for managing chronic idiopathic constipation (CIC), with variable efficacy. Vibrating capsule (VC) is a device that has shown variable results in alleviating constipation by tactile stimulation of the colonic wall and inducing peristalsis. This meta-analysis is to investigate the efficacy and safety of this modality. Methods: Comprehensive literature search was performed through June 14th, 2023, on databases including Embase, PubMed/MEDLINE, Cochrane Central, Web of Science, Global Index Medicus, and Google Scholar. Core concepts of VC, constipation, and bowel movement were searched. The DerSimonian-Laird method and random effects model were utilized. We calculated odds ratio (OR) and mean difference (MD) for proportional and continuous variables, respectively, with 95% confidence interval (CI) and a P value of <0.05 considered statistically significant. Results: The search strategy yielded 117 articles. Four studies with 705 total patients were finalized comparing VC to placebo/sham treatment. The pooled complete spontaneous bowel movement (CSBM), defined as bowel movement without use of laxatives within the last 48 hours with sense of complete evacuation did not achieve statistical improvement with VC (MD =0.153; 95% CI: -0.218 to 0.523; P=0.422). However, spontaneous bowel movement (SBM), defined as bowel movement without use of laxatives within the last 48 hours, showed statistical improvement with VC (MD =0.159; 95% CI: 0.095 to 0.223; P<0.001). VC didn't show an increase in pooled adverse events (OR =1.431; 95% CI: 0.702 to 2.916; P=0.324). Conclusions: The systematic review and meta-analysis suggest that VC is safe and efficacious in some outcomes, however, larger randomized controlled trials (RCTs) and real-world data are needed to establish this.

8.
J Med Life ; 16(7): 1050-1056, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37900062

RESUMO

In August 2022, the United States Food and Drug Administration issued marketing authorization for an orally administered vibrating colon-stimulating capsule for treating chronic idiopathic constipation. We aimed to review the literature systematically and synthesize evidence on the role of the vibrating capsule in chronic idiopathic constipation. A comprehensive search was conducted on PubMed, Embase, International Clinical Trials Registry Platform (World Health Organization), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) until 31 December 2022, to identify published pre-clinical and clinical original studies evaluating the role of the vibrating capsule in patients with chronic constipation. The studies were critically analyzed, and data were extracted. We identified thirty-three articles and five studies (one pre-clinical, one combined, and three clinical). The pre-clinical studies in dogs revealed no adverse effects of the vibrating capsule. In the clinical studies, there were significant findings observed. The number of spontaneous bowel movements per week and the proportion of patients experiencing an increase of at least one complete spontaneous bowel movement per week were both significantly higher in the group receiving the vibrating capsule compared to the group receiving the sham capsule. No treatment-related serious adverse event was noted. The mild adverse events were vibration sensation, diarrhea, and abdominal discomfort. The efficacy and safety profiles of the vibrating colon-stimulating capsule in treating patients with chronic constipation are promising. However, more robust evidence is required by conducting large randomized clinical trials before conclusively determining its wider use.


Assuntos
Colo , Constipação Intestinal , Estados Unidos , Humanos , Animais , Cães , Doença Crônica , Constipação Intestinal/tratamento farmacológico
9.
Cir Cir ; 90(5): 684-688, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36327467

RESUMO

We present the first pediatric case of Da Vinci Xi robot-assisted video sigmoidectomy in a 9-year-old male with chronic idiopathic constipation refractory to medical treatment and megarectosigmoid. He underwent sigmoidectomy with primary anastomosis without exceeding the peritoneal reflection. Sigmoidectomy in patients with intractable chronic constipation results in dramatic improvement, with reduction or elimination of laxative measures. Robot-assisted sigmoid resection is a safe minimally invasive alternative in the pediatric patient.


Se presenta el primer caso pediátrico de sigmoidectomía videoasistida por robot Da Vinci Xi en un varón de 9 años con constipación crónica idiopática refractaria al tratamiento médico y megarrectosigmoides. Se le realizó sigmoidectomía con anastomosis primaria sin rebasar la reflexión peritoneal. La sigmoidectomía en pacientes con constipación crónica intratable resulta en una notable mejoría, con reducción o eliminación de medidas laxantes. La resección del sigmoides con asistencia de robot es una alternativa de mínima invasión segura en el paciente pediátrico.


Assuntos
Robótica , Masculino , Humanos , Criança , México , Anastomose Cirúrgica , Constipação Intestinal/cirurgia , Estudos Retrospectivos
10.
Clin Exp Gastroenterol ; 14: 413-428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712055

RESUMO

Chronic idiopathic constipation (CIC) is a common functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. It has a great impact on the quality of life and on health care system and represents a heavy economic burden. The diagnosis is based on symptoms, classified by the Rome IV criteria. The aim of this review was to evaluate the current therapeutic guidelines for adult CIC and highlight new emerging treatments. In detail, European, French, Spanish and Korean guidelines have been identified and compared. Osmotic laxatives, and in particular polyethylene glycol, represent the first-line therapeutic approach. Stimulant laxatives are recommended as a second-line therapy. Pelvic floor rehabilitation is recommended in patients with ano-rectal dyssynergia. In patients who fail to improve with pharmacological therapies sacral nerve stimulation is considered as last chance before surgery. Surgical approach has however limited indications in selected cases. Inertia coli refractory to any approach and obstructed defecation are two subtypes which can benefit from surgery. Among emerging agents, prucalopride, a prokinetic agent, is recommended as a second-line treatment in refractory CIC patients. In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available.

11.
J Clin Med ; 10(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807888

RESUMO

Understanding pathophysiological causes of constipation is worthwhile in directing therapy and improving symptoms. This review aims to identify and fill gaps in the understanding of the pathophysiology of constipation, understand its prevalence, review diagnostic tools available to primary care physicians (PCPs), and highlight patients' expectations for the management of this common spectrum of disorders. Literature searches conducted via PubMed included terms related to constipation, diagnosis, and patient perceptions. Case studies were developed to highlight the differences between patients who may be appropriately managed in the primary care setting and those requiring specialty consultation. Myriad pathophysiological factors may contribute to constipation, including stool consistency, altered intestinal motility, gut microbiome, anorectal abnormalities, as well as behavioral and psychological factors. Common diagnoses of "primary constipation" include slow-transit constipation, defecation disorders, irritable bowel syndrome with constipation, and chronic idiopathic constipation. A detailed medical history should be conducted to exclude alarm features and PCPs should be familiar with pathophysiological factors that cause constipation, available diagnostic tools, alarm signs, and the various classification criteria for constipation subtypes in order to diagnose and treat patients accordingly. PCPs should understand when a referral to a gastroenterologist, anorectal specialist, pelvic floor physical therapist, and/or mental health specialist is appropriate.

12.
Int J Gen Med ; 14: 1457-1468, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907450

RESUMO

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are two common disorders of gut-brain interaction. Affected patients often first present to their primary care providers seeking care for symptoms of constipation, abdominal pain, and bloating, which have a significant impact on their health-related quality of life. These patients often require extensive counseling and reassurance, and knowledge of reliable diagnostic criteria and treatment options is imperative to managing their conditions. Family medicine practitioners, including nurse practitioners and physician assistants, are uniquely qualified to provide a diagnosis and safe, effective management of these disorders. This article reviews the latest evidence and provides practical advice related to diagnosis and management of IBS-C and CIC.

13.
Front Pediatr ; 9: 667225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33987155

RESUMO

Background: Non-pharmacologic auxiliary treatments have been considered crucial therapies for treating chronic idiopathic constipation (CIC) during the past decades worldwide. Several treatment patterns are available, but their relative efficacy is obscure because there are no head-to-head randomized controlled trials, especially in children. We conducted this network meta-analysis to evalute the effectiveness of these therapies in improving defecation function based on their direct comparisons with standard medical care. Methods: Medline, Embase, and Cochrane Central were searched for randomized controlled trials (RCTs) published in English from inception to October 2020, assessing the efficacy of auxiliary therapies (behavior therapy, physiotherapy, biofeedback, or anorectal manometry) in children with CIC. We extracted data for endpoints, risk of bias, and evidence quality. Eligible studies in the meta-analysis reported the data of a dichotomous assessment of overall response to treatment (response or not) or defecation frequency per week after treatment. The hierarchical Bayesian network meta-analysis was used in the study. We chose a conservative methodology, random effects model, to pool data which could handle the heterogeneity well. The relative risk (RR) with 95% confidence intervals (CIs) was calculated for dichotomous outcomes. For continuous results, weighted mean difference (WMD) with related CIs was calculated. The included treatments were ranked to define the probability of being the best treatment. Results: Seven RCTs (838 patients) met inclusion and endpoint criteria. Based on an endpoint of the absence of constipation (Rome criteria) with laxatives allowed, physiotherapy plus standard medical care (SMC) had the highest probability (84%) to bethe most effective therapy. When the treatment response was defined as an absence of constipation with not laxatives allowed, biofeedback plus SMC ranked first (probability 52%). Physiotherapy plus SMC ranked first when the endpoint was based on defecation frequency per week with laxatives allowed (probability 86%). Conclusion: Almost all auxiliary therapies are effective complementary therapies for treating CIC, but they needed to be used simultaneously with SMC. Nevertheless, because of the small number of eligible studies and their small sample sizes, the differences in treatment duration and the endpoints, large sample RCTs with long-term follow-up are required for further investigation.

14.
Prz Gastroenterol ; 15(2): 103-118, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32550942

RESUMO

Chronic idiopathic constipation (CIC) has emerged as common problem for contemporary gastroenterology and is one of the most frequent complaints in primary care. Chronic idiopathic constipation significantly affects patients' quality of life and has an impact on global health and economy. Functional gastrointestinal disorders and bowel disorders, according to Rome IV criteria, result from inappropriate gut-brain interactions. The pathophysiology is complex and poorly understood, with evidence accumulating that gut microbiota can be implicated in the development and function of the enteric nervous system. Gut bacteria modulate gut barrier function, short chain fatty acid synthesis, and bile acid metabolism, factors which play roles in the gut peristalsis regulation. The high prevalence of CIC, with poor treatment outcomes, warrants searches for new forms of therapy, including probiotic therapies. Probiotics are often recommended by medical practitioners, but evidence-based utility in adults with CIC is uncertain. Recommendations/guidelines are often based on results from individual studies, rather than meta-analyses or umbrella reviews. Additionally, meta-analyses often indicate a group of probiotics rather than individual strains, and they create difficulty for physicians in making therapeutic choices. More CIC patient randomised clinical studies utilising well-defined strains, or combinations, are necessary.

15.
Clin Exp Gastroenterol ; 13: 255-265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765039

RESUMO

BACKGROUND: Chronic idiopathic constipation (CIC) is a functional gastrointestinal disorder with an estimated prevalence of 16% in the USA; however, the humanistic and economic burden of CIC is poorly characterized. AIM: This systematic literature review aimed to assess the humanistic and economic burden of CIC in adults in the USA. METHODS: Two systematic literature searches of English-language publications on the humanistic and economic burden of CIC in adults in the USA were conducted using electronic databases and other resources. Both searches included the terms "chronic idiopathic constipation" and "functional constipation". Specific terms used in the search on humanistic burden included "quality of life", "SF-36", "SF-12", and "PAC-QOL"; search terms for economic burden included "cost", "resource use", "absenteeism", and "productivity". RESULTS: Overall, 16 relevant articles were identified. Health-related quality of life (HRQoL) appeared to be reduced in patients with CIC compared with controls and the general US population. Abdominal (r=0.33-0.49), stool (r=0.23-0.33), and rectal symptoms (r=0.53) appeared to be associated with reduced HRQoL. Younger age and female sex were associated with reduced overall HRQoL and greater symptom severity. Direct outpatient costs were higher in patients with CIC than those without CIC (US$6284 vs US$5254). Patients with CIC and abdominal symptoms reported more days of disrupted productivity per month than those without abdominal symptoms (3.2 days vs 1.2 days). The overall prevalence of complementary and alternative medicine use by patients with CIC was similar to that in the general US population. CONCLUSION: The reduced HRQoL and increased costs associated with CIC indicate unmet therapeutic need in this disorder. Further research is required to better understand the humanistic and economic burden of CIC in the USA.

16.
Expert Opin Pharmacother ; 20(17): 2073-2080, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31557072

RESUMO

Introduction: Chronic idiopathic constipation (CIC) is a kind of constipation in which the patient experiences constipation more than 3 months without any identifiable cause. Prucalopride is one such treatment considered for relieving symptoms of CIC regarding due to its selectivity for the 5HT4 receptor.Areas covered: This article is based on a PubMed and clinicaltrials.gov search for studies undertaken over the past 19 years (2000-2019) using the following keywords either alone or in combination: Prucalopride, chronic idiopathic constipation, chronic constipation, 5HT4 receptor, Resolor and Motegrity.Expert opinion: Prucalopride should be considered as one of the safe options for the treatment of CIC especially when previous treatments have failed. It can be helpful in the treatment of constipation caused by irritable bowel syndrome or spinal cord injury, opioid-induced constipation, post-operative ileus, and intestinal/colonic pseudo-obstruction. The major drawback of prucalopride is its high cost, which makes it less accessible to all patients.


Assuntos
Benzofuranos/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Laxantes/uso terapêutico , Benzofuranos/efeitos adversos , Benzofuranos/farmacocinética , Doença Crônica , Ensaios Clínicos como Assunto , Meia-Vida , Humanos , Laxantes/efeitos adversos , Laxantes/farmacocinética , Receptores 5-HT4 de Serotonina/metabolismo , Resultado do Tratamento
17.
Expert Rev Clin Pharmacol ; 12(11): 1019-1026, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31575291

RESUMO

Introduction. Chronic idiopathic constipation (CIC) is a functional gastrointestinal disorder that is associated with an increased healthcare cost and an abnormally poor quality of life. Plecanatide is a natural analog to the peptide agonist of the guanylate cyclase-C (GC-C) receptor, uroguanylin. The conversion of guanosine 5-triphosphate to cyclic guanosine monophosphate results in an increased bowel fluid secretion. Plecanatide is a promising new agent for CIC unresponsive to current therapeutic regimes.Areas covered. A comprehensive online search of Medline and the Science Citation Index was made using the keywords 'plecanatide', 'guanylate cyclase-C agonists', and 'constipation', in various combinations. We reviewed the pharmacodynamics, pharmacokinetics, and metabolism of this agent, and the most significant studies regarding the clinical efficacy and safety of plecanatide in CIC therapy.Expert opinion. Experimental studies showed that plecanatide was significantly better than placebo in reducing CIC severity, straining, stool consistency, bowel movements and quality of life. Apart from limited cases of diarrhea, no serious adverse events were reported. However, few data are available on its long-term safety. Furthermore, patients' affordability of plecanatide can be limited by its costs. Finally, this new agent with a different way of action can be proposed in patients refractory to common therapy.


Assuntos
Constipação Intestinal/tratamento farmacológico , Agonistas da Guanilil Ciclase C/uso terapêutico , Peptídeos Natriuréticos/uso terapêutico , Adulto , Animais , Doença Crônica , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Agonistas da Guanilil Ciclase C/efeitos adversos , Agonistas da Guanilil Ciclase C/farmacologia , Humanos , Peptídeos Natriuréticos/efeitos adversos , Peptídeos Natriuréticos/farmacologia , Qualidade de Vida
18.
Am J Med ; 132(5): 572-575, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30550753

RESUMO

Chronic idiopathic constipation and irritable bowel syndrome with constipation are commonly encountered in ambulatory patients, but limited options exist for patients with persistent or severe symptoms following treatment with nonprescription products. Plecanatide (Trulance, Synergy Pharmaceuticals, New York, NY) is a 16-amino acid peptide analog of uroguanylin that stimulates guanylate cyclase-C receptors to increase chloride and bicarbonate secretion into the intestine and prevents the absorption of sodium ions, thereby increasing the secretion of water into the lumen. The influx of additional fluid accelerates intestinal transit, softens the stool, and facilitates easier defecation. Plecanatide is the second guanylate cyclase-C receptor agonist to be approved by the US Food and Drug Administration for chronic idiopathic constipation and irritable bowel syndrome, but plecanatide is unique because its effects are limited to the proximal small bowel.


Assuntos
Constipação Intestinal , Síndrome do Intestino Irritável/tratamento farmacológico , Peptídeos Natriuréticos/farmacologia , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/etiologia , Fármacos Gastrointestinais/farmacologia , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Receptores Acoplados a Guanilato Ciclase/metabolismo , Resultado do Tratamento
19.
Cureus ; 11(4): e4382, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-31218146

RESUMO

Chronic idiopathic constipation (CIC) can be defined as bowel movements that are difficult to pass, are not occurring frequently, or have incomplete evacuation during defecation. A high-fiber diet and laxatives are the commonly used treatments, but in many cases, they do not produce satisfactory results. The first line of treatment is osmotic laxatives. If there is no improvement, the second line is guanylate cyclase-C (GCC) agonists like linaclotide or prokinetic agents such as prucalopride. On December 14, 2018, the United States Food and Drug Administration (US FDA) approved prucalopride for treating chronic idiopathic constipation. Prucalopride is a prokinetic agent which works at the 5-hydroxytryptamine receptor 4 (5-HT4) as an agonist with greater receptor selectivity. Patients on prucalopride reported improved symptoms, quality of life and satisfaction. The most frequent adverse events were headaches and problems related to the gastrointestinal tract. Caution should be taken when using prucalopride in patients with impaired liver and renal function. In Canada, prucalopride has been approved for treatment of female patients with chronic idiopathic constipation who have failed therapy with at least two laxatives from different classes over a six-month period.

20.
J Pediatr Surg ; 54(11): 2311-2317, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31056347

RESUMO

BACKGROUND: At the severe end of the idiopathic constipation spectrum exist patients with chronic idiopathic constipation associated with an enormous megarectosigmoid, among whom few require surgery. We performed transanal proximal rectosigmoidectomy, involving preservation of a 5 cm rectal reservoir, to ameliorate inconsistent and unpredictable outcomes and fecal incontinence occurring in some patients operated on with other techniques. METHODS: We retrospectively observed patients with chronic idiopathic constipation with megarectosigmoid who underwent transanal proximal rectosigmoidectomy during July 2017-May 2018. We analyzed sex, age, operation indication, complications, functional outcome, and time of follow-up. We statistically compared the dosage of laxative before and after the procedure. RESULTS: Thirteen patients were included in the study. Median age during surgery was 8 years. In 9 cases, the indication for surgery was chronic intake of a daily high dose of Senna with failed weaning trials, and 4 had persistent fecal impaction with laxative-intolerance and refusal of rectal enemas. No intra/postoperative complications occurred. Currently, all 13 patients have daily voluntary bowel movements and no fecal accidents. Laxative dosage was significantly reduced (p = 0.007). Follow-up ranged 6-16 months. CONCLUSION: Preliminary results suggest transanal proximal rectosigmoidectomy as an adequate alternative for patients requiring surgery for chronic idiopathic constipation with megarectosigmoid. TYPE OF STUDY: Clinical research. LEVEL OF EVIDENCE: Level III.


Assuntos
Colectomia , Constipação Intestinal/cirurgia , Megacolo/cirurgia , Criança , Colectomia/efeitos adversos , Colectomia/métodos , Colo/cirurgia , Constipação Intestinal/tratamento farmacológico , Impacção Fecal , Feminino , Humanos , Laxantes/uso terapêutico , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos
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