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1.
J Pediatr Gastroenterol Nutr ; 78(4): 800-809, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38314885

RESUMO

OBJECTIVES: Adolescent and pediatric functional constipation (FC) is a common clinical problem. Currently, data on lubiprostone for the treatment of pediatric FC are scarce. This study investigated the efficacy and safety of lubiprostone in the treatment of pediatric FC. METHODS: In a single-blinded, randomized controlled study, we included 280 patients aged 8-18 years with FC. Patients were randomized either to a weight-based lubiprostone dose (n = 140) or conventional laxatives (n = 140), including lactulose, bisacodyl, or sodium picosulfate, for 12 weeks, followed by 4 weeks posttreatment follow-up. RESULTS: Improvement in constipation was achieved in 128 (91.4%) patients in the lubiprostone group, and in 48 (34.3%) patients of the conventional therapy group (p < 0.001) and was sustained after treatment discontinuation. One quarter of the lubiprostone group experienced the first spontaneous bowel motion within 48 h after dose initiation. A total of 75.7% of the lubiprostone group could achieve and sustain Bristol stool form of 3 or 4 during the last 4 weeks of therapy and through the 4 weeks of follow-up versus 50 (35.7%) patients in the conventional therapy group (p < 0.001). No life-threatening adverse drug reactions were encountered, and no treatment-related discontinuation. Mild self-limited colicky abdominal pain and headache were the most prevalent side effects in the lubiprostone group. CONCLUSIONS: Lubiprostone is an effective and well-tolerated pharmacotherapy for youthful age and pediatric age groups, which may alter the paradigm of pediatric FC treatment.


Assuntos
Constipação Intestinal , Laxantes , Humanos , Adolescente , Criança , Lubiprostona/uso terapêutico , Laxantes/uso terapêutico , Lactulose/uso terapêutico , Bisacodil/uso terapêutico , Resultado do Tratamento
2.
BMC Med ; 21(1): 119, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36991404

RESUMO

Severe malaria is a potentially fatal condition that requires urgent treatment. In a clinical trial, a sub-group of children treated with rectal artesunate (RAS) before being referred to a health facility had an increased chance of survival. We recently published in BMC Medicine results of the CARAMAL Project that did not find the same protective effect of pre-referral RAS implemented at scale under real-world conditions in three African countries. Instead, CARAMAL identified serious health system shortfalls that impacted the entire continuum of care, constraining the effectiveness of RAS. Correspondence to the article criticized the observational study design and the alleged interpretation and consequences of our findings.Here, we clarify that we do not dispute the life-saving potential of RAS, and discuss the methodological criticism. We acknowledge the potential for confounding in observational studies. Nevertheless, the totality of CARAMAL evidence is in full support of our conclusion that the conditions under which RAS can be beneficial were not met in our settings, as children often failed to complete referral and post-referral treatment was inadequate.The criticism did not appear to acknowledge the realities of highly malarious settings documented in detail in the CARAMAL project. Suggesting that trial-demonstrated efficacy is sufficient to warrant large-scale deployment of pre-referral RAS ignores the paramount importance of functioning health systems for its delivery, for completing post-referral treatment, and for achieving complete cure. Presenting RAS as a "magic bullet" distracts from the most urgent priority: fixing health systems so they can provide a functioning continuum of care and save the lives of sick children.The data underlying our publication is freely accessible on Zenodo.


Assuntos
Antimaláricos , Artemisininas , Malária , Criança , Humanos , Pré-Escolar , Artesunato/uso terapêutico , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Administração Retal , Malária/tratamento farmacológico , Encaminhamento e Consulta , Bisacodil/uso terapêutico
3.
Antimicrob Agents Chemother ; 66(6): e0029222, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35652314

RESUMO

Identifying novel antivirals requires significant time and resource investment, and the continuous threat of viruses to human health necessitates commitment to antiviral identification and development. Developing antivirals requires years of research and validation, and recent outbreaks have highlighted the need for preparedness in counteracting pandemics. One way to facilitate development is to repurpose molecules already used clinically. By screening such compounds, we can accelerate antiviral development. Here, we screened compounds from the National Institutes of Health's Developmental Therapeutic Program for activity against chikungunya virus, an alphavirus that is responsible for a significant outbreak in the Americas in 2013. Using this library, we identified several compounds with known antiviral activity, as well as several novel antivirals. Given its favorable in vitro activity and well-described in vivo activity, as well as its broad availability, we focused on bisacodyl, a laxative used for the treatment of constipation, for follow-up studies. We find that bisacodyl inhibits chikungunya virus infection in a variety of cell types, over a range of concentrations, and over several rounds of replication. We find that bisacodyl does not disrupt chikungunya virus particles or interfere with their ability to attach to cells, but, instead, bisacodyl inhibits virus replication. Finally, we find that bisacodyl is broadly antiviral against a variety of RNA viruses, including enteroviruses, flaviviruses, bunyaviruses, and alphaviruses; however, it exhibited no activity against the DNA virus vaccinia virus. Together, these data highlight the power of compound screening to identify novel antivirals and suggest that bisacodyl may hold promise as a broad-spectrum antiviral.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Antivirais/farmacologia , Antivirais/uso terapêutico , Bisacodil/farmacologia , Bisacodil/uso terapêutico , Febre de Chikungunya/tratamento farmacológico , Humanos , Replicação Viral
4.
Am J Gastroenterol ; 115(6): 895-905, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32324606

RESUMO

OBJECTIVES: Chronic idiopathic constipation (CIC) is characterized by unsatisfactory defecation and difficult or infrequent stools. CIC affects 9%-20% of adults in the United States, and although prevalent, gaps in knowledge remain regarding CIC healthcare seeking and medication use in the community. We recruited a population-based sample to determine the prevalence and predictors of (i) individuals having discussed their constipation symptoms with a healthcare provider and (ii) the use of constipation therapies. METHODS: We recruited a representative sample of Americans aged 18 years or older who had experienced constipation. Those who met the Rome IV criteria for irritable bowel syndrome and opioid-induced constipation were excluded. The survey included questions on constipation severity, healthcare seeking, and the use of constipation medications. We used multivariable regression methods to adjust for confounders. RESULTS: Overall, 4,702 participants had experienced constipation (24.0% met the Rome IV CIC criteria). Among all respondents with previous constipation, 37.6% discussed their symptoms with a clinician (primary care provider 87.6%, gastroenterologist 26.0%, and urgent care/emergency room physician 7.7%). Age, sex, race/ethnicity, marital status, employment status, having a source of usual care, insurance status, comorbidities, locus of control, and constipation severity were associated with seeking care (P < 0.05). Overall, 47.8% of respondents were taking medication to manage their constipation: over-the-counter medication(s) only, 93.5%; prescription medication(s) only, 1.3%; and both over-the-counter medication(s) and prescription medication(s), 5.2%. DISCUSSION: We found that 3 of 5 Americans with constipation have never discussed their symptoms with a healthcare provider. Furthermore, the use of prescription medications for managing constipation symptoms is low because individuals mainly rely on over-the-counter therapies.


Assuntos
Constipação Intestinal/tratamento farmacológico , Laxantes/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Fatores Etários , Bisacodil/uso terapêutico , Doença Crônica , Colonoscopia/estatística & dados numéricos , Constipação Intestinal/fisiopatologia , Fibras na Dieta/uso terapêutico , Ácido Dioctil Sulfossuccínico/uso terapêutico , Serviço Hospitalar de Emergência , Emprego , Etnicidade/estatística & dados numéricos , Feminino , Gastroenterologistas , Fármacos Gastrointestinais/uso terapêutico , Agonistas da Guanilil Ciclase C/uso terapêutico , Humanos , Seguro Saúde/estatística & dados numéricos , Controle Interno-Externo , Lactulose/uso terapêutico , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Medicamentos sem Prescrição/uso terapêutico , Peptídeos/uso terapêutico , Médicos de Atenção Primária , Polietilenoglicóis/uso terapêutico , Senosídeos/uso terapêutico , Índice de Gravidade de Doença , Fatores Sexuais , Tensoativos/uso terapêutico , Inquéritos e Questionários , Estados Unidos
5.
Scand J Gastroenterol ; 54(1): 27-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30700194

RESUMO

OBJECTIVES: Bisacodyl and sodium picosulfate are classified both as stimulant laxatives, approved for short-term treatment of constipation and sold without prescription (OTC). Stimulant laxatives are associated with harmful long-term colonic effects and possible carcinogenic risk - and evidence support that these agents are used for longer periods. We aimed to compile and review the clinical trial evidence describing the effectiveness and safety of long-term treatment (>14 continuous days) with stimulant laxatives. METHODS: The PubMed database was searched for all randomised clinical trials (RCTs) examining the effect of bisacodyl or sodium picosulfate in adult patients diagnosed with constipation. RESULTS: Five RCTs (one open-label and four double-blinded) with intervention periods of four weeks duration were eligible. These included 1008 patients, whereof 26% dropped out. A positive global assessment of efficacy was obtained in 78-99% of the patients treated with bisacodyl or sodium picosulfate. Notably, the same global assessment was obtained in 46-54% of the placebo-treated patients. Compared to placebo, an improvement in stool consistency and a significant increase in number of bowel movements peer week were seen in favor of bisacodyl and sodium picosulfate. However, for pyridostigmine, a significant difference was seen compared to bisacodyl. AEs were generally mild, but frequent (up to 72%) mostly diarrhea and abdominal pain. CONCLUSION: The evidence base does not support use of stimulant laxatives for more than four weeks. Due to the substantial use of stimulant laxatives including sold OTC, longer term RCTs and epidemiological studies investigating effects and safety on the longer term are warranted.


Assuntos
Constipação Intestinal/tratamento farmacológico , Laxantes/efeitos adversos , Laxantes/uso terapêutico , Bisacodil/efeitos adversos , Bisacodil/uso terapêutico , Citratos/efeitos adversos , Citratos/uso terapêutico , Colo/efeitos dos fármacos , Colo/patologia , Constipação Intestinal/patologia , Humanos , Assistência de Longa Duração , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/uso terapêutico , Picolinas/efeitos adversos , Picolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Pharm Belg ; (2): 4-9, 2016 Jun.
Artigo em Francês | MEDLINE | ID: mdl-30281225

RESUMO

Obstipation is a common complaint in pharmacies and one of the treatment strategies is the delivery of enteric coated bisacodyL tablets. This article reviews the different aspects that are important for pharmacists to guarantee patient safety: whether medical treatment is required or not, which advice should be given on how to use the drug, and to conclude what is the analytical quality of the commercial products on the Belgian market.


Assuntos
Bisacodil/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Laxantes/uso terapêutico , Bélgica , Bisacodil/efeitos adversos , Humanos , Laxantes/efeitos adversos , Assistência Farmacêutica , Farmácia
7.
Scand J Gastroenterol ; 50(8): 1039-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25862428

RESUMO

OBJECTIVE: Low-volume polyethylene glycol (PEG) bowel preparations have been developed to improve compliance for colonoscopy. Our study aimed to compare the efficacy and tolerability of low-volume PEG containing ascorbic acid for colonoscopy against 2 L of PEG plus bisacodyl. METHODS: We prospectively enrolled consecutive inpatients who had not undergone polypectomy at the index colonoscopy and were subsequently referred for polypectomy at our hospital. A total of 62 patients were randomized to receive either low-volume PEG containing ascorbic acid (n = 31) or 2 L of PEG plus bisacodyl (n = 31) as a split-dose regimen in inpatients. The efficacy of preparation was determined using the Ottawa Bowel Preparation Score (OBPS) and a 4-point scale. Adverse events, tolerability, and willingness were evaluated using a questionnaire. RESULTS: Based on the OBPS and 4-point scale, we determined that the efficacy of low-volume PEG containing ascorbic acid was comparable to that of the 2 L of PEG plus bisacodyl (p = 0.071 for OBPS, p = 0.056 for the 4-point scale). Adverse events were comparable between the two groups (p = 1.000). A greater proportion of patients in the low-volume PEG containing ascorbic acid (90.6%) and the 2L of PEG plus bisacodyl (96.9%) were willing to repeat the same preparation for subsequent colonoscopy. CONCLUSION: Low-volume PEG containing ascorbic acid had comparable efficacy and tolerability to 2 L of PEG plus bisacodyl, when given as a split dose, for colonoscopy in inpatients. Split-dose low-volume PEG containing ascorbic acid is a good alternative for bowel preparation for colonoscopy in inpatients.


Assuntos
Ácido Ascórbico/uso terapêutico , Bisacodil/uso terapêutico , Catárticos/uso terapêutico , Colonoscopia/métodos , Polietilenoglicóis/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Inquéritos e Questionários
8.
Gastrointest Endosc ; 80(3): 482-91, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24830577

RESUMO

BACKGROUND: No bowel preparation for colonoscopy is optimal with regard to efficacy, safety, and tolerability. New options for bowel preparation are needed. OBJECTIVE: To compare a new hybrid preparation consisting of a reduced dose of oral sulfate solution (OSS) plus 2 L of sulfate-free electrolyte lavage solution (SF-ELS) with 2 low-volume preparations based on polyethylene glycol electrolyte lavage solution (PEG-ELS). DESIGN: Two randomized, controlled trials. SETTING: Twenty-four U.S. centers. PATIENTS: A total of 737 outpatients undergoing colonoscopy. INTERVENTIONS: In study 1, OSS plus SF-ELS was given as a split dose, and in study 2, OSS plus SF-ELS was given in its entirety the evening before colonoscopy. In study 1, the active control was 2 L of PEG-ELS plus ascorbic acid (PEG-EA) given as a split dose. In study 2, the control was 10 mg of bisacodyl plus 2 L of SF-ELS taken the evening before colonoscopy. MAIN OUTCOME MEASUREMENTS: Rates of successful (good or excellent) bowel preparation. RESULTS: In study 1, the rates of successful (excellent or good) preparation with OSS plus SF-ELS and PEG-EA were identical at 93.5% for split-dose preparation. OSS plus SF-ELS was noninferior to PEG-EA (P < .001). In study 2, OSS plus SF-ELS resulted in successful preparation in 89.8% of patients compared with 83.5% with bisacodyl plus SF-ELS in a same-day preparation regimen. OSS plus SF-ELS was noninferior to bisacodyl plus SF-ELS (P <.001). In study 1, vomiting was more frequent with OSS plus SF-ELS (13.5% vs 6.7%; P = .042), and bloating was rated worse with PEG-EA (P = .025). In study 2, overall discomfort was rated worse with OSS plus SF-ELS (mean score 2.1 vs 1.8; P = .032). There were no deaths in either study and no serious adverse events considered related to the preparation. LIMITATIONS: Bowel cleansing was not scored by colon segment. Adenoma detection was not compared between the regimens. CONCLUSION: OSS plus SF-ELS is a new, safe, and effective bowel preparation for colonoscopy.


Assuntos
Catárticos/uso terapêutico , Colonoscopia/métodos , Eletrólitos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Sulfatos/uso terapêutico , Idoso , Ácido Ascórbico/uso terapêutico , Bisacodil/uso terapêutico , Feminino , Humanos , Sulfato de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Método Simples-Cego
9.
Am J Gastroenterol ; 108(3): 401-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23318484

RESUMO

OBJECTIVES: Optimal bowel preparation is vital for the efficacy and safety of colonoscopy. The inconvenience, discomfort, required consumption of large volumes of product, and potential adverse effects associated with some bowel preparations deter patients from colonoscopy and may provide inadequate cleansing. A dual-action, non-phosphate, natural orange-flavored, low-volume preparation containing sodium picosulfate and magnesium citrate (P/MC) is currently being reviewed for bowel cleansing. METHODS: This was a phase 3, randomized, multicenter, assessor-blinded, prespecified non-inferiority, head-to-head study to investigate the efficacy, safety, and tolerability of day-before administration of P/MC vs. 2L polyethylene glycol solution and two 5-mg bisacodyl tablets (2L PEG-3350 and bisacodyl tablets (HalfLytely and Bisacodyl Tablets Bowel Prep Kit)) in adult patients preparing for colonoscopy (SEE CLEAR II Study). The primary objective of the study was to demonstrate the non-inferiority of P/MC to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing using a modified Aronchick scale. In addition, efficacy in the ascending, mid (transverse and descending), and recto-sigmoid segments of colon was evaluated using a modified Ottawa scale. Patient acceptability and tolerability of the bowel preparations were assessed via a standard questionnaire. Safety was assessed based on the monitoring of adverse events (AEs) and meaningful findings on clinical evaluations including physical examinations, vital sign measurements, and electrocardiograms (ECGs). RESULTS: A total of 603 patients were randomized to receive either P/MC (n = 300) or 2L PEG-3350 and bisacodyl tablets (n = 303). Based on the Aronchick scale, successful overall cleansing was similar in patients receiving P/MC (83.0%) and patients receiving 2L PEG-3350 and bisacodyl tablets (79.7%). P/MC demonstrated non-inferiority to 2L PEG-3350 and bisacodyl tablets in overall cleansing of the colon, as measured by the Aronchick scale. Similarly, the efficacy of P/MC, as measured by the Ottawa scale, was non-inferior to 2L PEG-3350 and bisacodyl tablets in cleansing the ascending, mid, and recto-sigmoid segments of the colon. Patient-reported acceptability and tolerability for each item examined on the questionnaire was significantly greater for P/MC compared with 2L PEG-3350 and bisacodyl tablets (P<0.0001).Treatment-emergent AEs related to the bowel preparation reported by 1% of patients receiving P/MC or 2L PEG-3350 and bisacodyl tablets were nausea (3.0% vs. 4.3%), vomiting (1.4% vs. 2.0%), and headache (2.7% vs. 1.7%). No clinically meaningful changes were noted in either treatment arm in data collected from physical examinations, vital sign measurements, and ECGs. CONCLUSIONS: When administered as a day-before dose, the bowel cleansing effects of P/MC were non-inferior compared with 2L PEG-3350 and bisacodyl tablets using the clinician-rated Aronchick and Ottawa scales. Treatment acceptability was significantly more favorable in patients receiving P/MC than in patients receiving 2L PEG-3350 and bisacodyl tablets.


Assuntos
Bisacodil/uso terapêutico , Catárticos/uso terapêutico , Citratos/uso terapêutico , Ácido Cítrico/uso terapêutico , Colonoscopia/métodos , Compostos Organometálicos/uso terapêutico , Picolinas/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bisacodil/administração & dosagem , Catárticos/administração & dosagem , Citratos/administração & dosagem , Ácido Cítrico/administração & dosagem , Colo/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Satisfação do Paciente , Picolinas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Inquéritos e Questionários
10.
Neurogastroenterol Motil ; 35(5): e14543, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37096634

RESUMO

BACKGROUND: Colonic high-amplitude propagating contractions (HAPC) are generally accepted as a marker of neuromuscular integrity. Little is known about low-amplitude propagating contractions (LAPCs); we evaluated their clinical utility in children. METHODS: Retrospective review of children with functional constipation undergoing low-resolution colon manometry (CM) recording HAPCs and LAPCs (physiologic or bisacodyl-induced) in three groups: constipation, antegrade colonic enemas (ACE), and ileostomy. Outcome (therapy response) was compared to LAPCs in all patients and within groups. We evaluated LAPCs as potentially representing failed HAPCs. KEY RESULTS: A total of 445 patients were included (median age 9.0 years, 54% female), 73 had LAPCs. We found no association between LAPCs and outcome (all patients, p = 0.121), corroborated by logistic regression and excluding HAPCs. We found an association between physiologic LAPCs and outcome that disappears when excluding HAPCs or controlling with logistic regression. We found no association between outcome and bisacodyl-induced LAPCs or LAPC propagation. We found an association between LAPCs and outcome only in the constipation group that cancels with logistic regression and excluding HAPCs (p = 0.026, 0.062, and 0.243, respectively). We found a higher proportion of patients with LAPCs amongst those with absent or abnormally propagated (absent or partially propagated) HAPCs compared to those with fully propagated HAPCs (p = 0.001 and 0.004, respectively) suggesting LAPCs may represent failed HAPCs. CONCLUSIONS/INFERENCES: LAPCs do not seem to have added clinical significance in pediatric functional constipation; CM interpretation could rely primarily on the presence of HAPCs. LAPCs may represent failed HAPCs. Larger studies are needed to further validate these findings.


Assuntos
Bisacodil , Motilidade Gastrointestinal , Humanos , Criança , Feminino , Masculino , Bisacodil/uso terapêutico , Motilidade Gastrointestinal/fisiologia , Constipação Intestinal , Colo , Manometria
11.
Korean J Gastroenterol ; 80(1): 17-27, 2022 07 25.
Artigo em Coreano | MEDLINE | ID: mdl-35879059

RESUMO

Background/Aims: Constipation is a common gastrointestinal disease that reduces the quality of life and incurs considerable medical expenses. Bisacodyl and sodium docusate are generally used to treat constipation. This study assessed the effectiveness and safety of Goodmorning S Granule® (Hanpoong Pharm. Co., Ltd., Wanju, Korea) in functional constipation by a comparison with bisacodyl. Methods: A 2-week randomized, double-blind, active-controlled exploratory clinical trial was conducted to compare the treatment (Goodmorning S Granule®) with the control (bisacodyl). The efficacy was measured by the changes in transition, Bristol stool type, stomachache, clinical manifestation, defecation time after drug consumption, 36-item short-form survey (SF-36), and the results of improvement evaluation. The safety was evaluated by the incidence of adverse drug events and vital signs. Additional analyses were conducted by dividing the severity according to the proportion of Bristol Stool Scale types 1 and 2. Results: Subjects were randomized to the treatment (n=24) or control (n=26) groups. No significant differences were observed in demographics. After 2 weeks from the baseline, the changes in the complete spontaneous bowel movement (CSBM) were higher in the treatment (4.00±2.62) group than in the control group (1.40±2.34) (p<0.05). The treatment group exhibited significant improvement in the score on the SF-36 questionnaire. The clinical side effects, such as stomachache and borborygmus, were reduced in the moderate constipation patients in the treatment group, according to additional analyses. Conclusions: Goodmorning S Granule®, a herbal medicine, was more effective in improving quality of life and CSBM per week and safer in the moderate constipation groups because of the reduced clinical side effects.


Assuntos
Bisacodil , Qualidade de Vida , Dor Abdominal , Bisacodil/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Método Duplo-Cego , Humanos , Resultado do Tratamento
12.
J Pediatr Gastroenterol Nutr ; 52(4): 433-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21240024

RESUMO

BACKGROUND AND AIM: Fecal soiling is a challenging problem in some children after pull-through surgery for Hirschsprung disease (HSCR). The prevailing perception is that soiling results from overflow incontinence; however, its treatment with laxatives yields mixed results. Colonic manometry studies are reported to be normal in most patients in this population. The interpretation of these findings does not support the physiology of fecal overflow incontinence in these children. The aim of the present study was to define the physiology underlying daily, frequent fecal soiling in children after surgery for HSCR using manometric techniques. PATIENTS AND METHODS: Four pediatric motility centers in the United States participated in the study; medical records and manometric tracings (anorectal and colonic) of children (n = 59; 6.5 years; 48 boys) who had pull-through surgery for HSCR and presented with daily, frequent fecal soiling were examined. Children referred for evaluation of constipation who had normal colonic manometry served as controls (n = 25; 6.7 years; 12 boys). The patients with HSCR were divided into 2 groups (Hirschsprung disease groups 1 and 2 [HD1, HD2]) based on the absence or presence of high-amplitude propagated contractions (HAPCs). A control group that included children with chronic constipation was also studied. We compared the mean HAPC frequency between the HD2 and control groups. RESULTS: HD1 included 21 patients who had no HAPCs in fasting or postprandial periods. HD2 included 38 patients who had an average of 0.07 HPACs/min while fasting and 0.13/min in the postprandial state. In this subset the number of HAPCs in the fasting state (P = 0.04) and the postprandial state (P < 0.001) was greater when compared with controls. Additionally, there was a significant increase in HAPCs/min from the fasting to the postprandial state (P = 0.01). In the HD2 group 40% had colonic hyperactivity. CONCLUSIONS: Daily, frequent fecal soiling after pull-through surgery for HSCR may be due to colonic hyperactivity in some children. It is imperative that this unique subset be identified because the management strategy would include avoidance of laxatives, contrary to standard current practice.


Assuntos
Colo/fisiopatologia , Colo/cirurgia , Incontinência Fecal/etiologia , Motilidade Gastrointestinal , Doença de Hirschsprung/fisiopatologia , Doença de Hirschsprung/cirurgia , Adolescente , Canal Anal/fisiopatologia , Bisacodil/farmacologia , Bisacodil/uso terapêutico , Criança , Pré-Escolar , Contraindicações , Incontinência Fecal/classificação , Incontinência Fecal/tratamento farmacológico , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Lactente , Laxantes/farmacologia , Laxantes/uso terapêutico , Masculino , Manometria , Prontuários Médicos , Período Pós-Prandial , Reto/fisiopatologia , Reto/cirurgia , Estudos Retrospectivos , Estados Unidos
13.
Neurogastroenterol Motil ; 33(10): e14123, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33751780

RESUMO

BACKGROUND: Bisacodyl is a member of the diphenylmethane family and is considered to be a stimulant laxative. It has a dual prokinetic and secretory action and needs to be converted into the active metabolite bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) in the gut to achieve the desired laxative effect. Bisacodyl acts locally in the large bowel by directly enhancing the motility, reducing transit time, and increasing the water content of the stool. A recent network meta-analysis concluded that bisacodyl showed similar efficacy to prucalopride, lubiprostone, linaclotide, tegaserod, velusetrag, elobixibat, and sodium picosulfate for the primary endpoint of ≥3 complete spontaneous bowel movements (CSBM)/week and an increase of ≥1 CSBM/week over baseline. The meta-analysis also found that bisacodyl may be superior to the other laxatives for the secondary endpoint of change from baseline in the number of spontaneous bowel movements per week in patients with chronic constipation. This observation stimulated the authors to review the available literature on bisacodyl, which has been available on the market since the 1950 s. PURPOSE: The aim of the current review was to provide an overview of the historic background, structure, function, and mechanism of action of bisacodyl. Additionally, we discuss the important features and studies for bisacodyl to understand its peculiar characteristics and guide its use in clinical practice, but also stimulate research on open questions.


Assuntos
Bisacodil , Constipação Intestinal , Bisacodil/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Defecação , Humanos , Intestino Grosso , Laxantes/farmacologia , Laxantes/uso terapêutico
14.
ANZ J Surg ; 90(1-2): 41-47, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31272135

RESUMO

BACKGROUND: Post-operative ileus (POI) and delayed return of gastrointestinal (GI) function are common complications after colorectal surgery. There is a lack of uniformity in enhanced recovery protocols (ERPs) with regards to interventions used to target these complications. This systematic review aims to categorize and summarize management recommendations available from published ERPs. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Library and PubMed databases was performed from January 1990 to May 2018. All studies publishing enhanced recovery or fast-track or multimodal pathway protocols for colorectal surgery in their full-text were included. Data on interventions aimed at reducing the duration of POI were extracted, as well as references quoted to support specific interventions. RESULTS: Of 481 manuscripts screened, 37 published ERPs were identified from 37 studies (18 cohort, seven historical-control, five guidelines, four randomized controlled trials, one randomized controlled trial protocol, one case series and one narrative review). The most commonly recommended interventions were magnesium-based laxatives (18 of 37, 48.6%), chewing gum (13 of 37, 35.1%), Alvimopan (6 of 37, 16.2%), lactulose (4 of 37, 10.8%), neostigmine (2 of 37, 5.4%) and bisacodyl (2 of 37, 5.4%). Geographical trends were noted for the various interventions, but high-quality evidence was only referenced to support the use of Alvimopan. CONCLUSION: ERP recommendations specific to interventions targeting POI and return of GI function are varied. While laxatives are the most commonly recommended intervention, there is only weak evidence reported to support this practice.


Assuntos
Doenças do Colo/cirurgia , Íleus/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Recuperação de Função Fisiológica , Doenças Retais/cirurgia , Bisacodil/uso terapêutico , Goma de Mascar , Humanos , Lactulose/uso terapêutico , Neostigmina/uso terapêutico , Piperidinas/uso terapêutico
15.
Neurogastroenterol Motil ; 32(8): e13851, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32281199

RESUMO

BACKGROUND: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment-refractory constipation. If bisacodyl does not induce high-amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies. METHODS: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion. RESULTS: One hundred and sixty-five children were included (median age 10, range 1-17 years; n = 96 girls). One thousand eight hundred and ninety-three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre- vs post-bisacodyl (Z = -0.53, P = .60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ2 (1)=7.04, P < .01). Site of bisacodyl administration, catheter type, and hospital location did not alter the response. CONCLUSIONS AND INFERENCES: Intraluminal bisacodyl induced HAPCs in 93% of children with treatment-refractory constipation. The bisacodyl response is characterized by ≥1 HAPC within 12 minutes of infusion. The majority of HAPCs terminate in a synchronous pressurization in the rectosigmoid. Optimal clinical management based upon colonic manometry findings is yet to be determined.


Assuntos
Bisacodil/farmacologia , Colo/efeitos dos fármacos , Constipação Intestinal/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Laxantes/farmacologia , Adolescente , Bisacodil/uso terapêutico , Criança , Pré-Escolar , Colo/fisiopatologia , Constipação Intestinal/fisiopatologia , Feminino , Motilidade Gastrointestinal/fisiologia , Humanos , Lactente , Laxantes/uso terapêutico , Masculino , Manometria , Estudos Retrospectivos , Resultado do Tratamento
16.
Can J Surg ; 52(2): 153-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19399212

RESUMO

The duration of postoperative ileus following abdominal surgery is quite variable, and prolonged postoperative ileus is an iatrogenic phenomenon with important influence on patient morbidity, hospital costs and length of stay in hospital. Adequate treatment for prolonged postoperative ileus is important to improve patient morbidity and clinical efficiency. Both clinical and pharmacological management strategies have improved rapidly over the last decade, and appropriate and timely management using multimodal techniques should be used for optimal care. In this review, we define postoperative ileus, describe the pathogenesis and briefly discuss clinical management before detailing potential pharmacologic management options.


Assuntos
Íleus/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Antagonistas Adrenérgicos alfa/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Bisacodil/uso terapêutico , Catárticos/uso terapêutico , Cisaprida/uso terapêutico , Di-Hidroergotamina/uso terapêutico , Humanos , Íleus/fisiopatologia , Inflamação/tratamento farmacológico , Naltrexona/análogos & derivados , Naltrexona/uso terapêutico , Neostigmina/uso terapêutico , Parassimpatomiméticos/uso terapêutico , Piperidinas/uso terapêutico , Propranolol/uso terapêutico , Compostos de Amônio Quaternário/uso terapêutico , Receptores Opioides mu/antagonistas & inibidores , Agonistas do Receptor de Serotonina/uso terapêutico
17.
Braz J Med Biol Res ; 51(7): e7372, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29846410

RESUMO

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.


Assuntos
Bisacodil/uso terapêutico , Catárticos/uso terapêutico , Colo/metabolismo , Constipação Intestinal/tratamento farmacológico , Trânsito Gastrointestinal/efeitos dos fármacos , Células Intersticiais de Cajal/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Animais , Colo/efeitos dos fármacos , Colo/patologia , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Feminino , Trânsito Gastrointestinal/fisiologia , Imuno-Histoquímica , Células Intersticiais de Cajal/metabolismo , Células Intersticiais de Cajal/patologia , Ratos , Ratos Wistar
18.
MMW Fortschr Med ; 149(44): 39-42, 2007 Nov 01.
Artigo em Alemão | MEDLINE | ID: mdl-18078169

RESUMO

Up to 60% of the patients with diabetes mellitus suffer from gastrointestinal tract symptoms that arise pathogenetically from a disturbance of the autonomous nervous system. Patient age, disease duration and poor control of diabetes mellitus correlate positively with the presence of gastrointestinal symptoms. Chronic constipation, in addition to diarrhoea, gall bladder dysfunction and incontinence, is increasingly regarded as a serious problem and for the first time, is now considered in the current guidelines of the professional societies. Modern diagnosis and treatment facilitate systematic control of the symptoms. Treatment necessitates long-term intake of laxatives, proper diabetes control and other accompanying general measures such as adequate amounts of liquids, dietary fibre and exercise. Motility and secretion-stimulating, osmotically active or locally applied laxatives are used. Slow transit constipation, which is typically observed in diabetics, can be best controlled with polyethylene glycol, bisacodyl or sodium picosulphate.


Assuntos
Constipação Intestinal/etiologia , Complicações do Diabetes , Bisacodil/uso terapêutico , Catárticos/uso terapêutico , Doença Crônica , Constipação Intestinal/diagnóstico , Constipação Intestinal/diagnóstico por imagem , Constipação Intestinal/dietoterapia , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/terapia , Diagnóstico Diferencial , Exercício Físico , Trânsito Gastrointestinal , Humanos , Polietilenoglicóis/uso terapêutico , Radiografia
19.
Eur J Pharm Sci ; 102: 172-179, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28279763

RESUMO

A doubly enteric-coated multiple-unit tablet (DET) of bisacodyl (BD) was formulated to selectively deliver the stimulant laxative to the large intestine. Solubilized BD in surfactants was adsorbed into the porous carrier and primarily coated with different combinations of pH-sensitive polymers (Eudragit S and Eudragit L) and time-dependent release polymer (Eudragit RS). BD-loaded granules were compressed into tablets and coated again with pH-sensitive polymers (Eudragit S:Eudragit L=1:1). The multiple-unit tablet was optimized with respect to the granular coating compositions (Eudragit S:Eudragit L:Eudragit RS=5:1:4) and coating level (12.5%), and coating level on the tablet (25%), by evaluating in vitro release profile in continuous dissolution medium. Drug release from the optimized tablet was effectively retarded in the simulated gastric and small intestinal fluids (below 7%), but profound drug liberation was attained in the colonic fluid (over 50%). On the other hand, drug release from the marketed product (Dulcolax®, Boehringer Ingelheim Pharma), a reference drug, in the gastric and small intestinal fluids was reached to 30%, while that in the colonic fluid was only 7%. In an in vivo efficacy study in loperamide-induced constipated rabbits, a remarkable recovery in fecal secretion was observed in the DET-treated group 24h post-dosing, compared to vehicle-treated (p<0.05) and the marketed product-treated groups (p<0.05). Moreover, pharmacokinetic evaluation in the constipated rabbits revealed that the DET system significantly lowered the systemic exposure compared with the marketed product (p<0.05), by hindering drug release in the upper intestine, a preferential absorption site. Therefore, the novel colon-targeted delivery system may be an alternative for boosting pharmacological responses in the colon, while diminishing the intestinal irritation and/or systemic adverse effect of the stimulant laxative.


Assuntos
Bisacodil/administração & dosagem , Sistemas de Liberação de Medicamentos , Mucosa Intestinal/metabolismo , Laxantes/administração & dosagem , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Animais , Bisacodil/química , Bisacodil/farmacocinética , Bisacodil/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo , Liberação Controlada de Fármacos , Excipientes/administração & dosagem , Excipientes/química , Suco Gástrico , Concentração de Íons de Hidrogênio , Absorção Intestinal , Secreções Intestinais , Laxantes/química , Laxantes/farmacocinética , Laxantes/uso terapêutico , Coelhos , Solubilidade , Comprimidos com Revestimento Entérico/administração & dosagem , Comprimidos com Revestimento Entérico/química
20.
Aliment Pharmacol Ther ; 21(12): 1491-5, 2005 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-15948817

RESUMO

BACKGROUND: A colon free of faecal residue is required for accurate diagnostic colonoscopy. Patient tolerance of his/her colonoscopy cathartic regimen affects patient compliance and willingness to undergo repeated examinations. AIM: To determine whether a meal could be consumed during standard bowel preparation. METHODS: This was a randomized, endoscopists' blinded comparison of the tolerability and efficacy of a prepackaged, low-residue diet (NutraPrep) combined with the LoSo Prep bowel cleansing system, which contains magnesium citrate, bisocodyl tablets and a bisocodyl suppository (NP-LS regimen), compared with a clear liquid diet and a double-dose sodium phosphate (Fleet Phospho-soda) regimen (2F regimen). Outcome measures included efficacy of bowel preparation, patient preparation tolerability, side-effects and patient safety. RESULTS: A total of 506 patients completed the study, 222 randomized to 2F and 284 to NP-LS. The NP-LS regimen resulted in significantly better colon cleansing in terms of the proportion with good or excellent results (P = 0.025) and in significantly better patient tolerance and willingness to repeat the cathartic preparation (P < 0.01). CONCLUSION: The NP-LS regimen proved superior to the 2F regimen.


Assuntos
Bisacodil/uso terapêutico , Catárticos/uso terapêutico , Ácido Cítrico/uso terapêutico , Colonoscopia/métodos , Fibras na Dieta/administração & dosagem , Compostos Organometálicos/uso terapêutico , Fosfatos/uso terapêutico , Enema/métodos , Feminino , Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Método Simples-Cego , Paladar
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