Treatment Of Constipation In Adults Research Articles

Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia on Diagnosis and Treatment of Constipation in Adults

Aim. Current clinical recommendations are intended to supply gastroenterologists, physicians and general practitioners with modern methods for the diagnosis and treatment of constipation.Key points. Constipation is defined as primary (functional) and secondary form, the latter comprising a manifestation of another illness. The causes of constipation are diagnosed with colonoscopy, especially in patients aged over 50 having “anxiety symptoms” and hereditary colorectal oncological predisposition. Indications may also include the bowel transit time estimation with radiopaque markers, balloon expulsion test, anorectal manometry, defecography and electromyography. Therapy for constipation should be comprehensive and concern lifestyle, diet recommendations and use of medications (psyllium, macrogol, lactulose, lactitol, contact laxatives, prucalopride). Patients with a less effective conservative therapy and largely reduced quality of life should be considered for surgical intervention.Conclusion. An effective therapy for constipation requires a correct diagnosis of its causes.

Use of prucalopride in adults with chronic idiopathic constipation

ABSTRACTIntroduction: Prucalopride is a selective 5-HT4 receptor agonist with colonic prokinetic activity. It was recently approved by the FDA for the treatment of chronic idiopathic constipation. Before this approval, there were limited options to improve colonic motility in the treatment of chronic idiopathic constipation.Areas covered: We systematically searched PubMed, Embase, ClinicalTrials.gov, and international conference presentations, and we reviewed all studies that evaluated prucalopride for the treatment of chronic idiopathic constipation in adults. In this review, we discuss the pharmacokinetics, pharmacodynamics, receptor interactions, phase I-IV clinical trials, and safety outcomes of prucalopride in adults, including the elderly.Expert opinion: Prucalopride is an effective agent to improve colonic motility, decrease colonic transit time, and increase complete spontaneous bowel movements in patients with chronic idiopathic constipation. Unlike previously available 5-HT4 receptor agonists such as cisapride and tegaserod, prucalopride does not interact with the cardiac hERG potassium channels or other serotonergic receptors in blood vessels and is not associated with an increase in major adverse cardiovascular events. Additionally, prucalopride has demonstrated promise in the treatment of gastroparesis, post-operative ileus, and opioid-induced constipation. Prucalopride directly stimulates colonic motility, differentiating it from all other medications (exclusively osmotic or chloride secretagogues) approved for chronic constipation in the last decade.

Lubiprostone for Constipation in Adults with Cystic Fibrosis: A Pilot Study

Constipation is prevalent in the cystic fibrosis (CF) population and yet there are few data demonstrating the effectiveness of currently used treatments. Lubiprostone is a laxative that works by activating the type 2 chloride channel in the gastrointestinal tract and thus has the potential to be especially effective for constipation associated with CF. To evaluate the effectiveness of lubiprostone for the treatment of constipation in adults with CF. In this pilot study, participants acted as their own controls and comparisons were made between run-in and treatment periods. During the 2-week run-in period, participants continued their usual treatment for constipation; during the 4-week treatment period, participants received lubiprostone 24 μg twice daily. Efficacy outcomes included spontaneous bowel movement frequency, Bristol Stool Scale scores, and Patient Assessment of Constipation Symptoms (PAC-SYM) survey scores. Outcomes were assessed during both the run-in and treatment periods (0, 2, and 4 weeks of treatment). Safety outcomes included spirometry, body weight, and serum chemistry. Seven participants completed the study. Mean (SD) baseline forced expiratory volume in 1 second was 83.0% (9.4) of predicted and body mass index was 24.0 (2.8) kg/m², indicating an overall healthy, well-nourished group of adults with CF. Lubiprostone improved overall symptoms of constipation as measured by PAC-SYM survey scores (1.18 [0.56], 0.54 [0.27], and 0.44 [0.36] at 0, 2, and 4 weeks, respectively; p < 0.001). Spontaneous bowel movement frequency and Bristol Stool Scale scores were not statistically significantly different between periods. There were no differences in safety measures. Transient chest tightness and shortness of breath were reported by 2 separate participants, although neither participant withdrew due to these adverse effects. Lubiprostone may be an effective option for the treatment of constipation in adults with CF.

Quality of life in children and adults with constipation

This review summarises the literature on quality of life (QOL) assessments in both children and adults with functional constipation. Studies of adults with constipation include subjects from both tertiary care centres and population-based surveys whereas there are no population-based studies in children. The preponderance of evidence indicates that the adverse effects of chronic constipation on QOL in both children and adults are comparable to that seen in other chronic gastrointestinal and non-gastrointestinal disorders. There are no data on the effect of treatment of children with constipation with regard to QOL whereas several studies indicate that successful treatment of constipation in adults has a favourable effect on QOL. The emerging concept in the treatment of chronic constipation is to measure both objective measures such as frequency and ease of defecation and subjective parameters such as QOL.

Use of the Chloride Channel Activator Lubiprostone for Constipation in Adults with Cystic Fibrosis: A Case Series

To describe the use of lubiprostone for constipation in 3 adults with cystic fibrosis (CF). This case series describes the use of lubiprostone for the treatment of constipation in 3 adults with CF (mean +/- SD length of therapy 17.3 +/- 1.5 mo). All 3 patients were prescribed lubiprostone 24 microg twice daily after hospitalization for treatment of intestinal obstruction. Patient 1 continues on chronic polyethylene glycol (PEG) 3350 and lubiprostone and has not had a recurrence of obstruction. Patient 2 requires aggressive chronic therapy with PEG 3350, lubiprostone, and methylnaltrexone. She has had 1 recurrence of obstruction. Patient 3 continues with lubiprostone taken several times per week with good control of constipation and no recurrence of obstruction to date. The adverse effect profile has been tolerable in all 3 patients. CF is caused by a genetic mutation resulting in a dysfunctional or absent CF transmembrane conductance regulator that normally functions as a chloride channel. This results in viscous secretions in multiple organ systems including the lungs and intestinal tract. Accumulation of viscous intestinal contents contributes to constipation, which is common among adults with CF and can sometimes lead to intestinal obstruction. Lubiprostone is indicated for chronic constipation and works by activating type 2 chloride channels (ClC-2) in the intestinal tract. Because it utilizes an alternate chloride channel, lubiprostone may be especially effective for constipation in patients with CF. Lubiprostone provides an additional option for the treatment of constipation in adults with CF. Its use in the CF population deserves further study.

Treatment of Idiopathic Chronic Constipation and Irritable Bowel Syndrome with Constipation: What Role for Lubiprostone?

Lubiprostone is a novel chloride channel 2 activator indicated for the treatment of chronic idiopathic constipation in adults and constipation-predominant irritable bowel syndrome (IBS-C) in adult women. It is effective for chronic constipation at a dose of 24 mcg twice daily and for IBS-C at a dose of 8 mcg twice daily. Lubiprostone is well-tolerated, with nausea and headache being the most commonly reported adverse drug reactions. It also has a low potential for drug-drug interactions. Lubiprostone is a potential treatment for both disorders, which have few treatment options available. Studies of longer duration will help more firmly establish its use for these chronic conditions.

Using methylnaltrexone in opioid-induced constipation

Methylnaltrexone (Relistor) is the first peripherally-acting mu (¼)-opioid receptor antagonist to be licensed for the treatment of opioid-induced constipation in adults with advanced illness receiving palliative care, when response to regular laxative therapy has been inadequate. Methylnaltrexone is a new drug in its own classification. It is not classed as a laxative but is designed to target the underlying cause of opioid-induced constipation by reversing the peripheral effects of opioids on the gastrointestinal tract. This article explores the uniqueness of the drug and how it has been used in clinical practice at the London Bridge Hospital.

Lubiprostone for constipation and irritable bowel syndrome with constipation

Chronic constipation and irritable bowel syndrome are heterogeneous disorders characterized by altered bowel habits, abdominal discomfort and/or difficult defecation. These conditions have a significant impact on patients’ quality of life, as well as on the US economy, both in terms of healthcare costs and lost productivity. Treatment typically begins with lifestyle changes, increased fiber intake and osmotic and stimulant laxative intake. However, treatments for constipation vary in terms of their efficacy and safety. Furthermore, surveys of physicians and patients have revealed a strong desire for improved therapeutic options. Lubiprostone is a synthetic bicyclic fatty acid that is gut selective and stimulates type 2 chloride channels, resulting in increased chloride, sodium and water secretion into the lumen. The increased fluid secretion causes luminal distension, secondary peristalsis and laxation. Randomized Phase III trials have shown that lubiprostone is efficacious in the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. The US FDA has approved lubiprostone at a dose of 24 µg twice daily for the treatment of chronic idiopathic constipation in adults, and at a dose of 8 µg twice daily for irritable bowel syndrome with constipation in adult women. Nausea, diarrhea and headaches are the most commonly reported side effects. In long-term studies, lubiprostone appears to be safe.

Relistor approved for opioid-related constipation

FDA has approved the marketing of methylnaltrexone bromide subcutaneous injection for the treatment of opioid-induced constipation in adults receiving palliative care for advanced illness. The product is sold by Wyeth Pharmaceuticals under the brand name Relistor. FDA-approved labeling for

M1706 Discontinuation of Lubiprostone Treatment for Irritable Bowel Syndrome with Constipation Is Not Associated with Symptom Increase or Recurrence: Results from a Randomized Withdrawal Study

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with an estimated prevalence of 10–15% in Western countries. • Diagnosis of IBS is based upon the presence of abdominal discomfort/pain with changes in bowel habits. In clinical practice and research, IBS patients are • subgrouped on the basis of differences in bowel habits. Approximately 1/3 of IBS patients suffer with IBS and constipation (IBS-C). Current therapies for IBS-C tend to target relieving individual symptoms of constipation, abdominal pain or bloating rather than the totality of IBS symptoms. • Lubiprostone, a selective activator of type-2 chloride channels (CIC-2), is approved for the treatment of chronic idiopathic constipation in adults and for the • treatment of IBS-C in adult women. Lubiprostone enhances fluid secretion into the intestinal lumen without altering serum electrolyte levels. • Patients with IBS may exhibit abnormal gut permeability and an associated intestinal inflammatory response. Lubiprostone stimulates recovery of mucosal • barrier function in animal models suggesting a possible mechanism for the clinical improvement observed in patients on this drug.* Given the intermittent nature of IBS-C symptoms, short-term interventions for symptomatic relief of IBS-C may be appropriate in some patients. Such • interventions need to be efficacious and not associated with rebound effects following discontinuation of treatment.

New Treatment Options in Childhood Constipation?

To date, the worldwide prevalence of symptoms of constipation in children varies widely and is estimated to range between 0.3–28%. Childhood constipation is recognized by infrequent, hard stools and the involuntary loss of faeces in the underwear. It is a debilitating condition that is often associated with abdominal pain. It causes distress to the child and to the family and can result in severe emotional disturbance and family discord. Importantly, childhood constipation often continues into adulthood and it is suggested that longstanding faecal impaction from childhood-on may result in a more complex pathophysiological end-state later in life (1). This again emphasizes the significance of an effective therapeutic intervention in children. To date however, treatment modalities are mainly based on empiricism and have little evidence of long-term efficacy. Although many compounds have been tried, there are little data to support there use. Moreover, there is a huge lack of large double-blind randomised controlled trials in children with well defined outcome measures. As in many more other fields in the medical treatment of children only a minority of the drugs used to treat constipated children have been studied adequately in the population, have appropriate use information on the product label and the information regarding safety and efficacy for pediatric patients is insufficient or absent. Currently acute simple constipation is usually treated with a high fibre diet and sufficient fluid intake, filling out a diary and toilet training. Based on the American medical position statement the treatment of chronic constipation consists of 4 important phases: 1) education, 2) disimpaction, 3) prevention of re-accumulation of faeces and 4) follow up (2). In this paper firstly recent advances in the treatment of constipation in adults and children are discussed, such as the selective 5-HT4, agonist, tegaserod, preand probiotics and sacral nerve stimulation. The second part will cover the use of polyethylene glycol which has been described as an effective and welltolerated treatment choice for pediatric constipation, especially as an adjunct to education and behavioural training. PEG 3350 and PEG 4000 have been proved an option for children with constipation who have failed or are intolerant of other pharmacotherapies. Serotonin plays a key role in mediating peristalsis and stimulating intestinal secretion via 5-HT4 receptors in the gut wall. Tegaserod, a selective agonist that acts at 5-HT4 receptors and increases small bowel transit, stimulates intestinal secretion and inhibits visceral afferent responses has proven effective in the treatment of chronic constipation in adults (3,4). Two randomized placebo controlled trials including more than 3000 patients with constipation showed a significant increase in spontaneous bowel movements per week and a significant reduction in straining, abdominal bloating/distension, and abdominal pain/discomfort. The most common adverse events, headache and abdominal pain, were more frequent with placebo than with tegaserod. In children with hard stools, caused by excessive straining, 5-HT4 agonist might benefit children with constipation and tendency to form hard stools, scybala and large rectal masses. This seems to be present more frequently in children.The role of this promising new agent in pediatric constipation has to be established in future studies. National and international collaboration to evaluate the efficacy of Tegaserod in children is of imminent importance to match similar quality and valuable results as described in adults with constipation. Researchers claim a positive effect on intestinal transit and stool consistency of preand probiotics. Nondigestible oligosaccharides consist mainly of fructooligosaccharides (FOS). FOS is a soluble dietary fibre, which reduces faecal pH, increases the water/holding capacity of stool and faecal weight and decreases intestinal transit time. Furthermore, it has prebiotic effects by selectively stimulating the growth of probiotic bacteria, such as bifidobacteria. A double-blind randomized controlled study in healthy infants comparing a fructooligosaccharide-supplemented cereal (0.75 g FOS per cereal serving) with placebo showed a significant increase in mean numbers of stool per infant and softer stools (5). The FOS supplemented cereal was well tolerated. In another study in healthy women, the probiotic strain Bifidobacterium animalis shortened both the total colonic transit time and the rectosigmoid transit time (6). However, the number of stools per week did not significantly change between the Bifidobacterium and M. A. Benninga, MD, PhD (e-mail: m.a.benninga@amc.uva.nl). Journal of Pediatric Gastroenterology and Nutrition 41:S56–S57 September 2005 Lippincott Williams & Wilkins, Philadelphia

Treatment of constipation in adults associated with idiopathic megarectum by behavioural retraining including biofeedback.

Constipation in adults associated with a grossly dilated rectum and recurrent faecal impaction, idiopathic megarectum, is rare. The aetiology of idiopathic megarectum is unknown, but may involve neuromuscular or behavioural factors. It is unknown whether the condition is reversible. This study aimed to determine the efficacy of behavioural therapy, including biofeedback, in such patients. Six patients (4 female; median age 27) with a history of rectal faecal impaction and a grossly dilated rectum on radiological examination were evaluated by structured questionnaire before, immediately after biofeedback therapy, and on follow-up. Physiological testing was performed before treatment, and 2 patients were evaluated by repeat physiological testing and contrast radiology on follow-up. On median follow-up of 18 months (range 11-27), five patients felt major and one patient minor improvement in symptoms, including two with complete symptom relief. Four patients came off laxatives without recurrent faecal impaction. In the 2 studied patients rectal size did not appear to decrease. Behavioural retraining, including biofeedback, improved symptoms in most patients with idiopathic megarectum. In some patients symptoms completely resolved, without the need for laxatives. Although further studies are necessary in terms of both larger number of patients and longer follow-up period, behavioural treatment may be useful for such patients.

New Polyethylene Glycol Laxative for Treatment of Constipation in Adults

New Polyethylene Glycol Laxative for Treatment of Constipation in Adults

New Polyethylene Glycol Laxative for Treatment of Constipation in Adults

New Polyethylene Glycol Laxative for Treatment of Constipation in Adults