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The American Journal of Gastroenterology Jun 2021Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for...
INTRODUCTION
Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations.
METHODS
We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor).
RESULTS
Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes, and ficus), and yogurt with galacto-oligosaccharide/prunes/linseed oil; and insufficient evidence (grade I) for polydextrose, inulin, and fructo-oligosaccharide. Diarrhea, nausea, bloating, and abdominal pain were common adverse events, but no serious adverse events were reported.
DISCUSSION
The spectrum of OTC products has increased and quality of evidence has improved, but methodological issues including variability in study design, primary outcome measures, trial duration, and small sample sizes remain. We found good evidence to recommend polyethylene glycol or senna as first-line laxatives and moderate evidence supporting fiber supplements, fruits, stimulant laxatives, and magnesium-based products. For others, further validation with more rigorously designed studies is warranted.
Topics: Bisacodyl; Cathartics; Chronic Disease; Citrates; Constipation; Defecation; Fruit; Gastrointestinal Agents; Glucans; Humans; Inulin; Laxatives; Magnesium; Nonprescription Drugs; Oligosaccharides; Organometallic Compounds; Picolines; Polyethylene Glycols; Psyllium; Senna Extract; Yogurt
PubMed: 33767108
DOI: 10.14309/ajg.0000000000001222 -
Neurogastroenterology and Motility Oct 2021Bisacodyl 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... (Review)
Review
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.
Topics: Bisacodyl; Constipation; Defecation; Humans; Intestine, Large; Laxatives
PubMed: 33751780
DOI: 10.1111/nmo.14123 -
Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis.The Lancet. Gastroenterology &... Nov 2019There are several drugs available for the treatment of chronic idiopathic constipation, but their relative efficacy is unclear because there have been no head-to-head... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are several drugs available for the treatment of chronic idiopathic constipation, but their relative efficacy is unclear because there have been no head-to-head randomised controlled trials. We did a network meta-analysis to compare the efficacy of these therapies in patients with chronic idiopathic constipation.
METHODS
We searched Medline, Embase, Embase Classic, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published from inception to week 3 June, 2019, to identify randomised controlled trials assessing the efficacy of drugs (osmotic or stimulant laxatives, elobixibat, linaclotide, lubiprostone, mizagliflozin, naronapride, plecanatide, prucalopride, tegaserod, tenapanor, or velusetrag) in adults with chronic idiopathic constipation. Participants had to be treated for a minimum of 4 weeks, and we extracted data for all endpoints preferentially at 4 weeks, 12 weeks, or both. Trials included in the analysis reported a dichotomous assessment of overall response to therapy (response or no response to therapy). We pooled the data using a random effects model, and reported efficacy and safety of all treatments as a pooled relative risk (RR) with 95% CIs to summarise the effect of each comparison tested. To rank treatments, we used P-scores, which measure the extent of certainty that a treatment is better than another treatment, averaged over all competing treatments.
FINDINGS
We identified 33 eligible randomised controlled trials of drugs, comprising 17 214 patients. Based on an endpoint of failure to achieve three or more complete spontaneous bowel movements (CSBMs) per week, the stimulant diphenyl methane laxatives bisacodyl and sodium picosulfate, at a dose of 10 mg once daily, were ranked first at 4 weeks (RR 0·55, 95% CI 0·48-0·63, P-score 0·99), and prucalopride 2 mg once daily ranked first at 12 weeks (0·82, 0·78-0·86, P-score 0·96). When response to therapy was defined as falilure to achieve an increase of one or more CSBM per week from baseline, diphenyl methane laxatives at a dose of 10 mg once daily ranked first at 4 weeks (0·44, 0·37-0·54, P-score 0·99), with prucalopride 4 mg once daily ranked first at 12 weeks (0·74, 0·66-0·83, P-score 0·79), although linaclotide 290 μg once daily and prucalopride 2 mg once daily had similar efficacy (P-scores of 0·76 and 0·71, respectively). Bisacodyl ranked last in terms of safety for total number of adverse events and abdominal pain (P-score 0·08).
INTERPRETATION
Almost all drugs studied were superior to placebo, according to either failure to achieve three or more CSBMs per week or or failure to achieve an increase of one or more CSBM per week over baseline. Although diphenyl methane laxatives ranked first at 4 weeks, patients with milder symptoms might have been included in these trials. Prucalopride ranked first at 12 weeks, and many of the included trials recruited patients who previously did not respond to laxatives, suggesting that this drug is likely to be the most efficacious for patients with chronic idiopathic constipation. However, because treatment duration in most trials was 4-12 weeks, the long-term relative efficacy of these drugs is unknown.
FUNDING
None.
Topics: Constipation; Humans; Laxatives; Randomized Controlled Trials as Topic
PubMed: 31474542
DOI: 10.1016/S2468-1253(19)30246-8 -
Journal of the American Association of... Sep 2022Chronic constipation is a common gastrointestinal condition, and most individuals self-treat with multiple over-the-counter (OTC) laxatives prior to consulting a health...
Chronic constipation is a common gastrointestinal condition, and most individuals self-treat with multiple over-the-counter (OTC) laxatives prior to consulting a health care provider. This brief report is a synopsis of an updated systematic review the authors conducted of published data on the efficacy and safety of OTC treatments to provide evidence-based recommendations. After applying the selection criteria, 41 randomized controlled clinical trials of ≥ 4-week duration were identified and analyzed. Standardized definitions of constipation were applied across these studies; however, definitions for stool frequency and consistency varied. Overall, the short- and long-term efficacy of polyethylene glycol-based preparations and senna were supported by good (grade A) evidence suggesting their use as first-line laxatives. Modest evidence (grade B) supported the use of other agents including the stimulants bisacodyl and sodium picosulfate, fiber, fruit-based laxatives, and magnesium oxide. Additional evidence from rigorously designed studies is needed to support the use of other options for chronic constipation. The OTC products studied were generally well tolerated with common adverse effects being abdominal pain, cramping, bloating, diarrhea, and nausea.
Topics: Constipation; Dietary Fiber; Humans; Laxatives; Nonprescription Drugs; Polyethylene Glycols; Treatment Outcome
PubMed: 35943487
DOI: 10.1097/JXX.0000000000000760 -
Annals of Gastroenterology 2021Diabetes mellitus is a risk factor for poor bowel preparation in patients who undergo colonoscopy, because of their decreased intestinal transit and slow gastric... (Review)
Review
Diabetes mellitus is a risk factor for poor bowel preparation in patients who undergo colonoscopy, because of their decreased intestinal transit and slow gastric emptying. This might lead to neoplastic or preneoplastic lesions being missed, longer procedural time, a higher risk of procedure-related adverse events, significant cost burden, patient dissatisfaction, and the need for a repeat colonoscopy. Multiple strategies have been suggested to improve bowel preparation in these patients. Proposed pharmacologic strategies include adding magnesium citrate, bisacodyl, lubiprostone or pyridostigmine. Non-pharmacologic strategies include preferential procedure scheduling or using a diabetes-specific preparation protocol. In this article, we present a comprehensive review of the literature and provide specific recommendations to general practitioners and gastroenterologists for improving bowel preparation in patients with diabetes.
PubMed: 33948054
DOI: 10.20524/aog.2021.0599 -
Antimicrobial Agents and Chemotherapy Jun 2022Identifying novel antivirals requires significant time and resource investment, and the continuous threat of viruses to human health necessitates commitment to antiviral...
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 activity and well-described 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.
Topics: Antiviral Agents; Bisacodyl; Chikungunya Fever; Chikungunya virus; Humans; Virus Replication
PubMed: 35652314
DOI: 10.1128/aac.00292-22 -
Frontiers in Pharmacology 2023Infants, children, and adolescents are at risk of experiencing a multitude of gastrointestinal disorders (GID). These disorders can adversely affect the quality of life... (Review)
Review
Infants, children, and adolescents are at risk of experiencing a multitude of gastrointestinal disorders (GID). These disorders can adversely affect the quality of life or be life-threatening. Various interventions that span the conventional and complementary therapeutic categories have been developed. Nowadays, parents increasingly seek complementary options for their children to use concurrently with conventional therapies. Due to the high prevalence and morbidity of diarrhea, constipation, and irritable bowel syndrome (IBS) in children, in this review, we decided to focus on the current state of the evidence for conventional and complementary therapies used for the treatment of these diseases in children. Diarrhea treatment focuses on the identification of the cause and fluid management. Oral rehydration with supplementation of deficient micronutrients, especially zinc, is well established and recommended. Some probiotic strains have shown promise in reducing the duration of diarrhea. For the management of constipation, available clinical trials are insufficient for conclusive recommendations of dietary modifications, including increased use of fruit juice, fiber, and fluid. However, the role of laxatives as conventional treatment is becoming more established. Polyethylene glycol is the most studied, with lactulose, milk of magnesia, mineral oil, bisacodyl, and senna presenting as viable alternatives. Conventional treatments of the abdominal pain associated with IBS are poorly studied in children. Available studies investigating the effectiveness of antidepressants on abdominal pain in children with IBS were inconclusive. At the same time, probiotics and peppermint oil have a fair record of benefits and safety. The overall body of evidence indicates that a careful balance of conventional and complementary treatment strategies may be required to manage gastrointestinal conditions in children.
PubMed: 36778015
DOI: 10.3389/fphar.2023.1051442 -
American Journal of Physiology.... Apr 2020Characterization of high-amplitude propagating pressure waves (HAPWs or HAPCs) plays a key role in diagnosis of colon dysmotility using any type of colonic manometry....
Characterization of high-amplitude propagating pressure waves (HAPWs or HAPCs) plays a key role in diagnosis of colon dysmotility using any type of colonic manometry. With the introduction of high-resolution manometry, more insight is gained into this most prominent propulsive motor pattern. Here, we use a water-perfused catheter with 84 sensors with intervals between measuring points of 1 cm throughout the colon, for 6-8 h, in 19 healthy subjects. The catheter contained a balloon to evoke distention. We explored as stimuli a meal, balloon distention, oral prucalopride, and bisacodyl injection, with a goal to optimally evoke HAPWs. We developed a quantitative measure of HAPW activity, the "HAPW Index." Our protocol elicited 290 HAPWs. 21% of HAPWs were confined to the proximal colon with an average amplitude of 75.3 ± 3.3 mmHg and an average HAPW Index of 440 ± 58 mmHg·m·s. 29% of HAPWs started in the proximal colon and ended in the transverse or descending colon, with an average amplitude of 87.9 ± 3.1 mmHg and an average HAPW Index of 3,344 ± 356 mmHg·m·s. Forty-nine percent of HAPWs started and ended in the transverse or descending colon with an average amplitude of 109.3 ± 3.3 mmHg and an average HAPW Index of 2,071 ± 195 mmHg·m·s. HAPWs with and without simultaneous pressure waves (SPWs) initiated the colo-anal reflex, often abolishing 100% of anal sphincter pressure. Rectal bisacodyl and proximal balloon distention were the most optimal stimuli to evoke HAPWs. These measures now allow for a confident diagnosis of abnormal motility in patients with colonic motor dysfunction. High-amplitude propagating pressure waves (HAPWs) were characterized using 84 sensors throughout the entire colon in healthy subjects, taking note of site of origin, site of termination, amplitude, and velocity, and to identify optimal stimuli to evoke HAPWs. Three categories of HAPWs were identified, including the associated colo-anal reflex. Proximal balloon distention and rectal bisacodyl were recognized as reliable stimuli for evoking HAPWs, and a HAPW Index was devised to quantify this essential colonic motor pattern.
Topics: Adult; Colon; Female; Gastrointestinal Motility; Humans; Male; Manometry; Middle Aged; Muscle Contraction; Young Adult
PubMed: 32068445
DOI: 10.1152/ajpgi.00386.2019