Stimulant Laxatives Research Articles

Saudi Experts Consensus on Diagnosis and Management of Pediatric Functional Constipation.

Although functional gastrointestinal disorders (FGIDs) are very common in pediatric patients, there is a scarcity of published epidemiologic data, characteristics, and management patterns from Saudi Arabia, which is the 2nd largest Arabic country in terms of area and the 6th largest Arabic country in terms of population, with 10% of its population aged <5 years. Functional constipation (FC) is an FGID that has shown a rising prevalence among Saudi infants and children in the last few years, which urges us to update our clinical practices. Nine pediatric consultants attended two advisory board meetings to discuss and address current challenges, provide solutions, and reach a Saudi national consensus for the management of pediatric constipation. The pediatric consultants agreed that pediatricians should pay attention to any alarming signs (red flags) found during history taking or physical examinations. They also agreed that the Rome IV criteria are the gold standard for the diagnosis of pediatric FC. Different therapeutic options are available for pediatric patients with FC. Dietary treatment is recommended for infants with constipation for up to six months of age. When non-pharmacological interventions fail to improve FC symptoms, pharmacological treatment with laxatives is indicated. First, the treatment is aimed at disimpaction to remove fecal masses. This is achieved by administering a high dose of oral polyethylene glycol (PEG) or lactulose for a few days. Subsequently, maintenance therapy with PEG should be initiated to prevent the re-accumulation of feces. In addition to PEG, several other options may be used, such as Mg-rich formulas or stimulant laxatives. However, rectal enemas and suppositories are usually reserved for cases that require acute pain relief. In contrast, infant formulas that contain prebiotics or probiotics have not been shown to be effective in infant constipation, while the use of partially hydrolyzed formula is inconclusive. These clinical practice recommendations are intended to be adopted by pediatricians and primary care physicians across Saudi Arabia.

Circadian rhythm and its potential influence on gut motility

The gastrointestinal system exhibits circadian fluctuations in activity that are under control of central and peripheral mechanisms. Disturbance of such rhythms may be associated with symptoms like constipation. Available evidence shows that stimulant laxatives such as bisacodyl can act synchronized on circadian colonic fluctuations helping to restore physiological gut rhythms.

Herbal Medicines for Constipation and Phytochemical Comparison of Active Components

Constipation is a very common medical condition worldwide, negatively affecting patients' quality of life and healthcare system. Rhubarb, senna leaf, and aloe are three frequently used herbal medications for achieving regular bowel movement. Rhubarb is also a key ingredient in MaZiRenWan, a Chinese medicine formula used every so often for constipation in oriental countries. We reviewed and summarized the major chemical components from these three botanicals, including dianthrones, anthraquinone glycosides, free anthraquinones, and other polyphenols. The purgative actions of these constituents have been compared. Anthraquinone, especially its dianthrone compounds such as sennoside A and sennoside B, as natural stimulant laxatives, possesses significant effects to promote gastrointestinal motility and relieve functional constipation. Furthermore, the safety, reported side effects, and other benefits of anthraquinone compounds are presented. To date, many anti-constipation natural products are being used but their research is relatively limited, and thus, more investigations in this field are indeed needed.

Diagnosis and Treatment of Elderly and Senile Chronic Constipation: an Expert Consensus

Aim. An appraisal of practitioners with chronic constipation management details in older and senile adults.Key points. Chronic constipation is a common issue in geriatrics. Aside to age-related physiological bowel disfunction, a higher constipation incidence is conditioned by declined physical activity and frailty, polypharmacy and a series of secondary constipation-developing chronic states and diseases. Chronic constipation is associated with a higher risk of cardiovascular disease and complications, impaired general perception of health and pain, growing alarm and depression, and reduced quality of life. The treatment tactics in chronic constipation is cause-conditioned and should account for the patient’s history and therapy line, overall clinical condition, cognitive status and functional activity level. An essential baseline aspect of constipation management is apprising the patient and his family of the underlying factors and methods for non-drug and drug correction. An higher-fibre diet is recommended as first measure, with osmotic laxatives added and titrated to clinical response if none observed towards the non-drug and high-fibre regimens. Stimulant laxatives and prokinetics should be recommended in patients reluctant to fibre supplements and osmotic laxatives. Subsidiary correction includes biofeedback, transanal irrigation, acupuncture, foot reflexology and percutaneous tibial nerve stimulation.Conclusion. Elderly and senile chronic constipation is a prevalent multifactorial state requiring an efficient management via assessment and correction of total risk factors and consistent use of non-medication and drug therapies.

Most children experience resolution of idiopathic pediatric rectal prolapse with bowel management alone

BackgroundRecent studies in children with idiopathic rectal prolapse report up to 48% require surgical intervention to manage refractory disease. We sought to examine outcomes of our non-surgical approach to managing rectal prolapse using a bowel management program. MethodsA retrospective review was performed for all children with the diagnosis of rectal prolapse between 2011 and 2020. Children with a rectal polyp or hemorrhoid were excluded. Results47 children with rectal prolapse were identified (median age at diagnosis of 4 years (IQR 3,7.75); age ≤ 4 years n = 30; age > 4 years n = 17). Associated diagnoses included constipation (n = 45, 96%) and psychiatric diagnoses (n = 7, 14%). Children underwent a bowel management program including stimulant laxatives in 44 (94%) and osmotic laxatives in 2 (4%). Median follow-up time was 181 days (IQR 77, 238). Median time to resolution of rectal prolapse was 9 months (IQR 4, 13) with a maximum time to resolution of 31 months. We compared children ≤ 4 years old (Group A) to those > 4 years old (Group B). Psychiatric diagnoses were less common in Group A (3.5 vs. 38.9%, p = 0.003). Median time to spontaneous resolution was 6.5 months (IQR 3.5, 9.5) in Group A versus 13.5 (IQR 4, 16) months in Group B, p = 0.13. No differences in surgical intervention were identified. Three (6.4%) patients required surgery for prolapse. ConclusionsA bowel management program is an effective treatment for most children with rectal prolapse. This data suggests that surgical intervention is unnecessary in most children. Level of evidenceIII.

Personality characteristics and medical impact of stimulant laxative abuse in eating disorder patients\u2014a pilot study

BackgroundStimulant laxative abuse as a purging behavior can be profound in those with eating disorders. However, the psychopathology leading to stimulant laxative abuse is poorly understood. Furthermore, the medical impact of stimulant laxative abuse has not been studied in this population.MethodsSix individuals abusing stimulant laxatives underwent a barium enema to assess for evidence of the cathartic colon syndrome and 29 individuals engaging in any purging behaviors completed the Tri-dimensional Personality Questionnaire-Short Form, Sensitivity to Punishment/Sensitivity to Reward Questionnaire-Short Form, Beck Depression Inventory, and the State Trait Anxiety Inventory questionnaires.ResultsThree of the six patients completing the barium enema had the radiographic findings consistent with cathartic colon. Individuals engaging in laxative abuse showed higher Novelty Seeking compared to those engaging in other forms of purging, and those engaging in any form of purging behavior showed greater Sensitivity to Punishment compared to Sensitivity to Reward. There was also the presence of greater Harm Avoidance than Reward Dependence in this population.ConclusionThere may be different psychopathology that contributes to the abuse of stimulant laxatives than that associated with other forms of purging. Regardless of the driving factor, further research is warranted to discover best therapeutic interventions given the potential to develop the cathartic colon syndrome with ongoing use of stimulant laxatives.Plain English SummaryCathartic colon is a condition whereby the colon, or lower intestine, is converted into an inert tube incapable of propagating fecal matter. It is thought to develop due to over-use of stimulant laxatives. However, it is unclear if this condition truly exists and whether it contributes to the constipation experienced by individuals with eating disorders who have extensive past histories of abusing laxatives. It is also unclear if laxative abuse presents with different medical complications than other forms of purging. The purpose of this study is to determine whether radiographic evidence of cathartic colon can be found in eating disorder patients abusing stimulant laxatives, whether there are different medical complications with laxative abuse versus other forms of purging, and to examine the psychological composition of individuals who engage in severe laxative abuse. Specifically, the authors investigated the interrelationship between Harm Avoidance and Reward Dependence, with emphasis on gaining a better understanding of Reward Dependence by examining both Sensitivity to Reward and Sensitivity to Punishment in patients who engage in severe laxative abuse. Our findings suggest that stimulant laxative abuse may cause the development of cathartic colon changes and that there may be unique psychopathology that contributes to the abuse of stimulant laxatives. Given the higher Novelty Seeking personality-dimension in those abusing laxatives, it is possible that this purging behavior may be considered addiction-like in nature, which would have distinct treatment implications.

Medical Management of Constipation in Elderly Patients: Systematic Review.

Background/AimsConstipation is a common gastrointestinal problem in the elderly. Because of the limitations of life style modifications and the comorbidity, laxative use is also very common. Therefore, this study reviews the latest literature on the effect and safety of laxative in the elderly.MethodsA systematic review of randomized controlled trials investigating the effectiveness and safety of laxatives for constipation in elderly patients over 65 years old were performed using the following databases PubMed, EMBASE, and the Cochrane Library.ResultsTwenty-three randomized controlled trials were included in this review. Among the selected studies, 9 studies compared laxative with placebo and 5 studies compared laxatives of the same type. Four studies compared different types of laxatives or compared combination agents. Five studies compared novel medications such as prucalopride, lubiprostone, and elobixibat with placebo. Psyllium, calcium polycarbophil, lactulose syrup, lactitol, polyethylene glycol, magnesium hydroxide, stimulant laxative with or without fiber, and other medications were more effective than placebo in elderly constipation patients in short-term. Generally, the frequency and severity of adverse effects of laxative were similar between the arms of studies.ConclusionsBulk laxative, osmotic laxative, stimulant laxative with or without fiber, and other medications can be used in elderly patients in short-term within 3 months with reasonable safety. However, the quality of included studies was not high and most of studies was conducted in a small number of patients. Among these laxatives, polyethylene glycol seems to be safe and effective in long-term use of about 6 months in elderly patients.

Superiority of mosapride citrate to picosulfate sodium as a laxative for withdrawal from regular enemas in children with severe functional constipation

Background: Severe functional constipation (FC) with low bowel movement frequency (BMF) of ?1 day/week and hard stools oftenrequires regularly repeated enemas or often leads to enema dependency (ED). Aim: The current study aimed to compare the efficacy of mosapride citrate (Mo) with the traditional stimulant laxative picosulfate sodium (Pi) for withdrawal from ED in children with severe FC. Results: Twenty-four treatment-naïve patients who met the Rome IV diagnostic criteria for FC seen at our center for 8 years from 2012 were enrolled. Glycerin enema was repeated until the BMF was ?3.5 days/week. Simultaneously, Mo at 0.3 mg/kg/day (n=11) or Pi at 0.25 mg/kg/day (n=13) was administered concomitantly with magnesium oxide or lactulose. The proportion of withdrawal from ED was significantly higher in the Mo group than Pi group during the 4 months observational period (90.9% vs. 46.2%, respectively; p=0.034) and shorter in time to withdraw from ED (0 vs. 3.5 months, respectively; p=0.015). Conclusion: Mo is more effective than Pi for withdrawal from ED in children with severe FC.

What is the Evidence for Over the Counter Laxatives to Treat Childhood Constipation?

Functional constipation is a common pediatric GI disorder that is responsible for a significant portion of pediatric office visits each year. It presents a significant stressor for patients, their families, and providers alike. There are a variety of over the counter agents available for treatment of pediatric constipation. Osmotic laxatives, such as polyethylene glycol 3350 (PEG 3350) and lactulose, remain the most effective and safe therapy for both long and short term treatment of pediatric functional constipation. Stimulant laxatives, like Senna and Bisacodyl, probiotics, fiber preparations, enemas, and suppositories make excellent choices for adjunct therapies in specific clinical scenarios. There are multiple over the counter pharmacologic agents with various mechanisms of action that have demonstrated efficacy in pediatric functional constipation. These therapies are generally safe and well tolerated by patients.

Sennoside A alleviates inflammatory responses by inhibiting the hypermethylation of SOCS1 in CCl4-induced liver fibrosis

Liver fibrosis is the consequence of chronic liver injury and is a major challenge to global health. However, successful therapy for liver fibrosis is still lacking. Sennoside A (SA), a commonly used clinical stimulant laxative, is reported to improve hepatic disease, but the underlying mechanisms remain largely elusive. Here, we show for the first time that SA enhanced suppressor of cytokine signaling 1 (SOCS1) expression in a DNA methyltransferase 1 (DNMT1)-dependent manner and thereby attenuated liver fibrosis. Consistently, SA inhibited the expression of the liver fibrogenesis markers α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) and suppressed inflammatory responses in vivo and in vitro. Coculture experiments with macrophages/hepatic stellate cells (HSCs) revealed that SA suppressed HSC proliferation by downregulating proinflammatory cytokines in macrophages. Mechanically, SA promoted the aberrant expression of SOCS1 in liver fibrosis. However, blocking SOCS1 expression weakened the inhibitory effect of SA on HSC proliferation, indicating that SOCS1 may play an important role in mediating the antifibrotic effect of SA. Furthermore, SA inhibited DNMT1-mediated SOCS1 and reduced HSC proliferation by inhibiting inflammatory responses in carbon tetrachloride (CCl4) -induced liver fibrosis.

Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options.

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.

Laxative Abuse Cessation Leading to Severe Edema

Stimulant laxatives are a common class of laxatives that is abused by patients with eating disorders. We present a case of a 30-year-old female who presented with dyspnea, peripheral edema and weight gain who had been chronically using laxatives. Her symptoms were consistent with rebound edema caused by sodium and free water shifts with abrupt cessation of excessive stimulant laxative use. This case highlights the use of furosemide as the mainstay treatment for rebound edema and weight gain.

Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel.

The prescribing and use of opioid analgesics is increasing in Italy owing to a profusion in the number and types of opioid analgesic products available, and the increasing prevalence of conditions associated with severe pain, the latter being related to population aging. Herein we provide the expert opinion of an Italian multidisciplinary panel on the management of opioid-induced constipation (OIC) and bowel dysfunction. OIC and opioid-induced bowel dysfunction are well-recognised unwanted effects of treatment with opioid analgesics that can profoundly affect quality of life. OIC can be due to additional factors such as reduced mobility, a low-fibre diet, comorbidities, and concomitant medications. Fixed-dose combinations of opioids with mu (μ) opioid receptor antagonists, such as oxycodone/naloxone, have become available, but have limited utility in clinical practice because the individual components cannot be independently titrated, creating a risk of breakthrough pain as the dose is increased. A comprehensive prevention and management strategy for OIC should include interventions that aim to improve fibre and fluid intake, increase mobility or exercise, and restore bowel function without compromising pain control. Recommended first-line pharmacological treatment of OIC is with an osmotic laxative (preferably polyethylene glycol [macrogol]), or a stimulant laxative such as an anthraquinone. A second laxative with a complementary mechanism of action should be added in the event of an inadequate response. Second-line treatment with a peripherally acting μ opioid receptor antagonist (PAMORA), such as methylnaltrexone, naloxegol or naldemedine, should be considered in patients with OIC that has not responded to combination laxative treatment. Prokinetics or intestinal secretagogues, such as lubiprostone, may be appropriate in the third-line setting, but their use in OIC is off-label in Italy, and should therefore be restricted to settings such as specialist centres and clinical trials.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01766-y.

Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial.

Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).

Bisacodyl in Stimulant Laxatives Can Induce Estrogen Agonist/Antagonist Activity in Breast Cancer Cells in Culture

Exposure to xenobiotic estrogens has the potential to induce estrogen activity that may contribute to a range of undesired physiological effects including the stimulation of estrogen responsive tumors. We have previously determined that extracts of OTC medications containing the stimulant laxative bisacodyl induce estrogenic activity in tissue culture bioassays. In this study, we tested the hypothesis that bisacodyl is responsible for the estrogen activity of these extracts and then characterized these effects. Ethanol extracts and dilutions were prepared from OTC medications containing Bisacodyl (1 gm:1 ml). The estrogen agonist and antagonist activity of each extract, as well as bisacodyl and then metabolite DA-bisacodyl was determined using the T47dkbluc estrogen reporter gene and the MCF-7 E3 estrogen responsive proliferation assays. LC-MS analysis was used to determine bisacodyl and DA-bisacodyl concentration in extracts as well as to trace the metabolism of bisacodyl to DA-bisacodyl in the cell culture bioassays. Molecular modeling “docking” simulations of the interactions of bisacodyl and the metabolite DA-bisacodyl with the estrogen receptor (ER) ligand binding domain was performed using MOE from Chemical Computing Group. Bisacodyl and the metabolite DA-bisacodyl induced mixed agonist/antagonist activity in MCF-7 E3 estrogen responsive proliferation assay similar to 4OH-tamoxifen. At the same time, both compounds stimulated only minimal estrogen activity in the T47dkbluc estrogen reporter gene assay. LC-MS analysis determinations identified that almost all bisacodyl was converted to the dihydroxy metabolite DA-bisacodyl in cell culture bioassays. Molecular modeling “docking” simulations determined that while bisacodyl does not fit into the agonist (estradiol) or antagonist (4OH-tamoxifen) conformations of the estrogen receptor ligand binding site, the metabolite DA-bisacodyl may fit into the antagonist induced binding pocket of the ER in a reasonable way. This study characterizes the observed estrogen activity of extracts from OTC medications containing bisacodyl as resulting from the bisacodyl metabolite DA-bisacodyl interacting with the estrogen receptor. Thus, bisacodyl is an OTC medication active ingredient that has potential to induce side effects and or toxicity involving estrogen signalling. The capacity for medications containing bisacodyl or other estrogenic substances to induce estrogen activity in patients is unclear. At the same time, consumers and practitioners should be aware of the potential estrogen activity of bisacodyl containing products.

Teeth discolouration and prescribed slimming magistral formula: a case report

Introduction Tooth discolouration is a common subject of aesthetic dissatisfaction for which patients seek dental care [1,2]. Discolouration can be extrinsic (chromogenic agents deposited on the tooth surface – enamel), intrinsic (chromogens deposited within the bulk of the tooth – dentin), and internalised discolouration, a combination of both [1,2]. Different factors can be accountable for dental staining, such as certain medicines, smoking, some foods/beverages (e.g. coffee, tea, wine), poor oral hygiene (e.g. chromogenic bacteria), advancing age, trauma or disease [3]. Medicines known to discolour teeth, especially during tooth development, include antibiotics, antihistamines, antihypertensives, antipsychotics and fluoride [2,3]. Yet, there are numerous drugs with scarce information in literature about its potential for tooth discolouration. To the best of our knowledge this is the first report of a patient´s tooth discolouration by staining, suspected to result from a prescribed magistral formula (MF) for weight loss. Materials and methods This study details a case of a non-smoking 51-year-old Caucasian woman presenting severely stained teeth and a clinical history of depression and pre-obesity, medicated with escitalopram (20 mg; antidepressant) and loflazepate (2 mg in SOS; anxiolytic). The patient referred taking hard gelatine capsules for weight loss (once daily for 3 weeks), prescribed as a MF; each unit was composed of chlordiazepoxide (8 mg; anxiolytic), phenolphthalein (PhP; 65 mg; laxative), furosemide (20 mg; diuretic), metformine (280 mg; antidiabetic), bupropion (120 mg; antidepressant), artichoke extract (110 mg; allegedly choleretic and diuretic), Citrus aurantium extract (150 mg; claimed stimulant and thermogenic). Written consent for data use was obtained from the patient. Results Several teeth presented discolouration by staining as dark brown spots, which together with the clinical history, allowed the establishment of aetiology and selection of treatment. The dental cleaning procedure (with ultrasound and final polishing with a zirconium silicate particles-based prophylaxis paste, without fluoride) was effective. Slimming MF was discontinued and staining did not reappear (up to 3 months), even though the patient maintained her other habits. Neither drugs, nor botanicals, in the patient’s MF were identified in literature as tooth stain-causing molecules. Discussion and conclusions The colour and type of staining is consistent with deposition of chromogens in tooth crests. Xerostomia, a common side-effect of the antidepressants, may have potentiated the chromogens' deposition, although the medicine did not enter in close contact with teeth. A systemic manifestation of the drug, as a result of a combination of intrinsic and extrinsic factors, is also possible. Stains may have originated from tainted plant extracts (containing tannins or uncontrolled/unlabeled heavy metals − Fe, Cu, Cd, Sn − due to phytogeography; contaminants) or PhP (an acid–base titration reagent, changing colour according to pH), here used as a stimulant laxative, withdrawn from medicines in many European countries due to its carcinogenic potential. The hypotheses raised warrant further investigation and clarification of the role of drugs/botanicals and contaminants in tooth staining.

Efficacy and Safety of Over-the-Counter Therapies for Chronic Constipation: An Updated Systematic Review.

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.

Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation.

BackgroundBisacodyl 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.PurposeThe 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.

Methylnaltrexone for Refractory Opioid-Induced Constipation in Hospitalized Cancer Patients—A Highly Effective Treatment (F415A)

1.Describe the overall efficacy of methylnaltrexone when prescribed to hospitalized cancer patients for opioid-induced constipation.2.Recognize the difference in response rates between patients receiving lower doses of opioids and those receiving higher doses of opioids. Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that has been studied in cancer and non-cancer patients with opioid-induced constipation (OIC), but only in the outpatient setting. For hospitalized patients with cancer pain and laxative-refractory OIC, its effectiveness is unknown. Describe the efficacy of methylnaltrexone on OIC in the inpatient setting. We performed a single-center, retrospective chart review of all hospitalized, adult patients with a cancer diagnosis who received methylnaltrexone from the palliative medicine team at our institution between January 1, 2012, and July 1, 2019. We identified 365 patients. The mean age was 57, 54% were male, and 82% were white. 360 patients (99%) received the 6 mg dose. The median oral morphine equivalent (OME) was 144 mg (range 0-4320mg). 58% (95% CI, 53-63%) had a bowel movement (BM) within 24 hours, and 73% (95% CI, 69-78%) had a BM within 48 hours. Higher OME was associated with successful BM. Patients with <150 OME had a response rate of 38% and patients with >150 OME had a response rate of 95% (p <0.001). Patients who received osmotic and stimulant laxatives prior to methylnaltrexone experienced no difference in response rates, although those who took stool softeners prior to receiving methylnaltrexone had a higher response rate. Methylnaltrexone is an effective treatment for OIC in the inpatient setting, especially for patients taking >150 OME.

Opioid-Induced Constipation and Acupuncture: A Case Discussion

BackgroundUse of acupuncture for treatment of functional constipation is well studied; however, studies examining use of acupuncture for opioid-induced constipation are limited. Case DescriptionA 70-year-old woman with newly diagnosed multiple myeloma discovered after presentation to the emergency room with severe back pain. Pain management required use of opioids, escalating to effect. Hospital course was complicated by opioid-induced constipation causing abdominal pain, nausea, and ileus despite aggressive titration of stimulant and osmotic laxatives as well as administration of suppositories and enemas on multiple occasions. Prior to nasogastric tube placement for the ileus, the patient requested acupuncture treatment in attempt to relieve constipation. Shortly after acupuncture session, patient passed multiple stools with improvement in abdominal pain and nausea and avoidance of nasogastric tube. ConclusionAcupuncture for opioid-induced constipation may provide symptom relief through use of nonpharmacologic interventions; however, further studies are needed to determine the optimal therapeutic approach.