Rome III criteria for chronic constipation Using simple visual descriptors, it illustrates the common stool forms and consistency on a 7-point scale. It has been validated in a number of studies and has been found to be easily understood by patients, enabling them to recognize and thus classify the stool type that most closely represents their own experience.
The form of the stool depends on the time that it spends in the colon; therefore, the BSFS is a quick and reliable indicator of transit time. It is particularly useful in patients with self-reported constipation who do not have infrequent bowel movements, to establish that hard or lumpy stools are, indeed, present. Routine extensive diagnostic and physiological testing is not recommended for chronic constipation. Barium enema plays a limited role today but can identify megacolon and megarectum. Anorectal manometry and histology of the nerve plexuses can be used to confirm Hirschsprung's disease.
As discussed earlier, constipation may arise secondary to a variety of factors Table 1. Hence, routine diagnostic testing is generally not recommended for chronic constipation. However, if there is suspicion of metabolic causes, these can be investigated with a complete blood cell count, biochemical profile, serum calcium, glucose levels and thyroid function tests. If these give rise to suspicion, serum protein electrophoresis, urine porphyrins, serum parathyroid hormone and serum cortisol levels can be considered, but this will only rarely be indicated.
Drugs commonly used in the treatment of constipation 41 , Well-designed, placebo-controlled, blinded, clinical trials of older laxatives are sparse. Although many trials report improvements in the number of bowel movements per week and some report improvements of certain symptoms, many studies are small and lack comprehensive clinically relevant treatment endpoints. Similarly, there is a lack of head-to-head comparisons; hence, there is a lack of evidence to determine whether one laxative class is superior to another. It is also largely unknown if laxative treatments address the impaired quality of life observed in patients with chronic constipation, as most studies have failed to assess quality of life measures.
Indeed, for some patients, laxatives can worsen certain symptoms, such as bloating and flatulence. Undigestible fibers attract water, which leads to a larger and softer fecal mass. Systematic reviews of older studies indicate that fiber increases the number of bowel movements, but the quality of these studies is inconsistent and the treatment duration was usually limited to 4 weeks or less. Most comparative data suggest that lactulose and polyethylene glycol PEG have similar efficacy, but with lower incidence of vomiting and flatulence associated with the latter. No treatment-related safety differences were observed between the PEG and placebo groups during the study, with the exception of GI complaints This difference was observed due to abdominal distension, diarrhea, loose stools, flatulence and nausea, which are considered usual effects of laxative use.
Stimulant laxatives act via the lumen to alter electrolyte transport and increase intraluminal fluid secretion; when in contact with the mucosa they indirectly stimulate sensory nerve endings, thereby stimulating propulsion. In summary, a wide variety of laxatives are available, many of which are effective and well-tolerated in most constipated patients. However, they are not effective in all patients, and for some, the mode of action or dosage schedule is unacceptable and leads to patient dissatisfaction. Grade 2 recommendations are supported by one or more well-designed cohort or case-controlled studies.
Recent controlled studies have established the efficacy of biofeedback in the management of chronic constipation in those with defecatory disorders, but the efficacy seems less in those with slow-transit constipation.
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However, recognizing and diagnosing defecatory disorders is beyond the scope of primary care practice, and is usually only done by gastroenterologists. Moreover, this therapy requires a patient who understands the concept and aim of the biofeedback process, and a skilled and motivated physiotherapist.
Availability of experienced therapists and reimbursement of biofeedback is problematic in most parts of Europe. Chloride channels play an important role in fluid transport and the maintenance of cell volume and pH in a variety of tissue and cell types, and in particular, in intestinal epithelial cells. Lubiprostone activates chloride channels to increase intestinal fluid secretion. As has already been discussed, serotonin is a critical component in the regulation of gut motility, visceral sensitivity, and intestinal secretion, acting via serotonin 5-HT 4 receptors, which are expressed mainly by ENS interneurones.
It is logical, therefore, to target 5-HT 4 receptors in developing treatments for constipation. Cisapride, a member of the substituted benzamide family, is a partial 5-HT 4 receptor agonist that was widely used for the treatment of gastro-esophageal reflux and dyspepsia before its withdrawal from the market in July It was associated with rare dose-dependent cardiac events, including lengthening of the QT interval, syncope, and ventricular arrhythmia in patients with predisposing conditions. Although the mechanisms underlying these adverse effects are not clear, they are unlikely to be related to 5-HT 4 effects.
Prucalopride is highly selective for the 5-HT 4 receptor, unlike cisapride, displaying at least fold selectivity for its therapeutic target receptor. In October , prucalopride received EU approval for the treatment of chronic constipation in women in whom laxatives fail to provide adequate relief, and now represents a new therapeutic option in the management of this condition. The therapeutic potential in hypomotile disorders of both the upper and lower GI tract, and the different pharmacological mode of action, might be the reason why the regulatory authorities have classified prucalopride in a separate class to laxatives WHO ATC classification A03AE, drugs for functional bowel disorders — acting on serotonin receptors.
Three mu-opioid antagonists naloxone, methylnaltrexone and alvimopan are currently under evaluation for the treatment of opiate-induced constipation 84 , 85 and postoperative ileus. Linaclotide is an agonist of guanylate cyclase-C receptors, which stimulates intestinal fluid secretion and transit. In early studies, it has been found to increase bowel movement frequency and loosen stool consistency.
A number of groups have provided recommendations for the diagnosis and treatment of constipation; 32 , 35 , 40 , 96 , 97 however, no standardized treatment guidelines have gained acceptance in general medical practice. Although the evidence for a number of interventions including modifications to diet and lifestyle is weak or contradictory, all the guidelines recommend that these be tried before pharmacological intervention.
In general, where treatment pathways are recommended, the sequence is:. Exclude other pathologies and secondary causes.
Begin treatment with dietary and lifestyle adjustments. Move to osmotic laxatives, stool softeners and bulk-forming agents — there is no consensus on the order in which these should be tried. Surgery should be used as a last resort or to treat identified disorders that require surgical correction.
Although prokinetic agents feature in the two sets of US guidelines Grade A recommendation , 40 , 55 these are now out of date. Tegaserod has now been limited to emergency use in the US and has not received licensing approval in the EU. Prucalopride has recently received EU approval for the treatment of chronic constipation in women in whom laxatives fail to provide adequate relief; this is not mentioned in the guidelines.
Once organic disorders and obstructions have been excluded, a functional bowel disorder is the most likely explanation for the constipation. Most patients with chronic constipation report minimal abdominal bloating or discomfort associated with their other symptoms of chronic constipation; however, in some patients, as symptoms often overlap, it may be difficult to distinguish chronic constipation and IBS-C.
Laxatives: A Practical Guide
As previously mentioned, guidelines and algorithms for the management and treatment of chronic constipation have not taken into account more recent therapeutic developments. Although a new set of Rome Foundation diagnostic algorithms covering the diagnosis and management of FGIDs including chronic constipation 35 and refractory constipation 36 have been recently published, newer agents have not been included. According to these guidelines, patients with constipation that is refractory to a high-fiber diet and traditional laxatives should be referred for physiological testing, such as anorectal manometry, rectal balloon expulsion, and colon transit.
Now, with the recent availability of prokinetic agents such as prucalopride, an additional therapeutic step can be added to these existing guidelines. Following this, if patients still experience continuous symptoms e. If constipation symptoms are refractory to pharmacological treatment, patients should be referred for physiological testing as outlined in the published Rome algorithm for refractive constipation and difficult defecation Fig.
Enterokinetic treatment algorithm. Once idiopathic chronic constipation has been identified Rome III ; and education, lifestyle and dietary measures; and treatment with laxatives response evaluable after 2—4 weeks have failed to provide adequate relief, an enterokinetic agent can be commenced response to prucalopride evaluable after 4—12 weeks.
If constipation symptoms are still refractory to pharmacological treatment, patients should be referred for physiological testing as outlined in the published Rome algorithm for refractive constipation and difficult defecation. Refractory constipation and difficult defecation. If there is no adequate response to therapy, further investigation may be considered at this point.
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The presence of a functional defecation disorder does not exclude the diagnosis of slow colonic transit. Thus, depending on the results of the colonic transit study, the patient can be characterized as suffering from a functional defecation disorder with slow 12 or normal colonic transit. If it is felt appropriate to distinguish between the two possibilities, the colonic transit evaluation may be repeated after correction of the defecation disorder.
If transit normalizes, the presumption is that the delay was secondary to the defecation disorder; if not, the delayed colonic transit is presumed to be a comorbid condition, which may require therapy if there is no clinical improvement with the treatment of functional defecation disorder. Constipation is common and for some it can be chronic, where symptoms can be severe and can significantly affect a patient's quality of life.
Although many laxative treatments are available, either OTC or by prescription, patients may often need additional treatment to achieve optimal symptom relief. As evidence for the effectiveness for many of the older laxatives is limited and there are relatively few guidelines on the management of this condition, treatment is often empirically-based.
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If diet, lifestyle measures, and traditional laxative therapies fail to provide adequate relief, the use of a motility agent offers a novel mechanism of action with therapeutic benefit. The 5-HT 4 agonist prucalopride, approved in the EU, increases colonic motility and is a valuable clinical option for the patient who is dissatisfied or incompletely treated by laxatives. Medical writing support in the development of this article was provided by Jude Douglass and Victoria Harvey, and was funded by Movetis. No financial interests.
National Center for Biotechnology Information , U. Neurogastroenterology and Motility. Neurogastroenterol Motil. Published online Mar Author information Article notes Copyright and License information Disclaimer. Received Sep Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2. This article has been cited by other articles in PMC. Abstract Background Although constipation can be a chronic and severe problem, it is largely treated empirically.
Purpose We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Keywords: algorithm, constipation, dissatisfaction, prokinetic, prucalopride. Introduction Constipation is very common and many or most people are affected at some time in their life.
Pathophysiology Constipation may be primary idiopathic or secondary to other factors Table 1. Cause Example Organic Colorectal cancer, extra-intestinal mass, postinflammatory, ischemic or surgical stenosis Endocrine or metabolic Diabetes mellitus, hypothyroidism, hypercalcemia, porphyria, chronic renal insufficiency, panhypopituitarism, pregnancy Neurological Spinal cord injury, Parkinson's disease, paraplegia, multiple sclerosis, autonomic neuropathy, Hirschsprung's disease, chronic intestinal pseudo-obstruction Myogenic Myotonic dystrophy, dermatomyositis, scleroderma, amyloidosis, chronic intestinal pseudo-obstruction Anorectal Anal fissure, anal strictures, inflammatory bowel disease, proctitis Drugs Opiates, antihypertensive agents, tricyclic antidepressants, iron preparations, anti-epileptic drugs, anti-Parkinsonian agents anticholinergic or dopaminergic Diet or lifestyle Low fiber diet, dehydration, inactive lifestyle.
Open in a separate window. Figure 1. Normal-transit constipation Normal-transit constipation is probably the most common form of constipation seen by general clinicians, although this has not formally been studied.
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Slow-transit constipation Approximately half of patients with symptoms refractory to supplementary fiber have a prolonged intestinal transit time. Defecation disorders A number of patients with chronic constipation display a difficulty in expelling stools from the rectum. Diagnosis of chronic constipation The duration and characteristics of the patient's symptoms must be assessed to distinguish chronic from transient constipation. Table 2 Rome III criteria for chronic constipation Diagnostic evaluation Routine extensive diagnostic and physiological testing is not recommended for chronic constipation.
Blood in the stool. Sudden change in bowel habit after the age of Significant abdominal pain. Family history of colon cancer or inflammatory bowel disease. Table 4 Evidence-based review of treatments for constipation. New pharmacological treatments for constipation Currently available treatments Lubiprostone Chloride channels play an important role in fluid transport and the maintenance of cell volume and pH in a variety of tissue and cell types, and in particular, in intestinal epithelial cells.
Prucalopride Prucalopride is highly selective for the 5-HT 4 receptor, unlike cisapride, displaying at least fold selectivity for its therapeutic target receptor. Experimental treatments Opioid antagonists Three mu-opioid antagonists naloxone, methylnaltrexone and alvimopan are currently under evaluation for the treatment of opiate-induced constipation 84 , 85 and postoperative ileus. Linaclotide Linaclotide is an agonist of guanylate cyclase-C receptors, which stimulates intestinal fluid secretion and transit. Review of currently available guidelines, recommendations and algorithms A number of groups have provided recommendations for the diagnosis and treatment of constipation; 32 , 35 , 40 , 96 , 97 however, no standardized treatment guidelines have gained acceptance in general medical practice.
In general, where treatment pathways are recommended, the sequence is: Exclude other pathologies and secondary causes.
Figure 2. Figure 3. Conclusions Constipation is common and for some it can be chronic, where symptoms can be severe and can significantly affect a patient's quality of life. References 1. Systematic review: impact of constipation on quality of life in adults and children. Aliment Pharmacol Ther. Johanson J, Kralstein J. Chronic constipation: a survey of the patient perspective. The burden of constipation on quality of life: results of a multinational survey. II [ Google Scholar ]. An epidemiological survey of constipation in Canada: definitions, rates, demographics, and predictors of health care seeking.
Am J Gastroenterol. Epidemiology of constipation EPOC study in the United States: relation of clinical subtypes to sociodemographic features. A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation. Eoff JC. Optimal treatment of chronic constipation in managed care: review and roundtable discussion. J Manag Care Pharm. Physiology of refractory chronic constipation.
Rao SSC. Constipation: evaluation and treatment. Gastroenterol Clin North Am. An examination of the reliability of reported stool frequency in the diagnosis of idiopathic constipation. Impaired colonic motor response to eating in patients with slow-transit constipation. Colonic mass movements in idiopathic chronic constipation. Response to a behavioral treatment, biofeedback, in constipated patients is associated with improved gut transit and autonomic innervation. Postprandial colonic transit and motor activity in chronic constipation.
Decreased interstitial cell of cajal volume in patients with slow-transit constipation. Impaired colonic motor response to cholinergic stimulation in patients with severe chronic idiopathic slow transit type constipation. Dig Dis Sci. Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome. Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation. Slow transit constipation: a disorder of pelvic autonomic nerves?
Steroid hormone abnormalities in women with severe idiopathic constipation. Role of progesterone signaling in the regulation of G-protein levels in female chronic constipation. Obstructive defecation: a failure of rectoanal coordination. Dyssynergic defecation. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Randomized controlled trial of biofeedback, sham feedback, and standard therapy for dyssynergic defecation.
Clin Gastroenterol Hepatol. Randomized, controlled trial shows biofeedback to be superior to alternative treatments for patients with pelvic floor dyssynergia-type constipation. Dis Colon Rectum. Functional bowel disorders. An evidence-based approach to the management of chronic constipation in North America. Kellow JE. Language English. Author Capasso, Francesco, author. Other Authors Gaginella, Timothy S. Constipation -- drug therapy.
Cathartics -- pharmacology. Internal medicine. Internal Medicine. Summary Constipation is a common disorder that is often defined differently by patients and physicians. The "normality" of bowel movements, in terms of frequency, varies among individuals; frequency that is thought by one person to be constipation may be reported by another to be usual and thus normal. Often the perceived "need" to have a bowel movement leads to self-treatment with laxatives as these drugs are widely available without a prescription.
This situation can raise problems in patient care, because of potential interactions between laxatives and other medications. Furthermore, chronic use abuse oflaxatives can cause serious medical consequences, causing patients to visit physicians, and even to be hospitalized for further evaluation and care. This has a financial impact on the patient, and on health care systems.
It is essential that pharmacists, physicians and other health care practitioners counsel patients on the causes of constipation and the proper use oflaxatives. A medical work-up by a physician should be done to determine if the constipation is due to a pathological process. Most laxatives in use today are of botanical origin.
Contents Ch. Introduction Ch. Constipation: the Rationale for Laxative Use Ch. Intestinal Motility and Laxative Action Ch. Laxatives of Botanical Origin Ch. Natural Laxatives of Mineral Origin Ch. Synthetic Laxatives Ch. Laxative Abuse Ch. Conclusions Ch. Notes Includes bibliographical references p. Bibliographic Level Mode of Issuance: Monograph. Also available in print. Electronic reproduction. Other Form Technical Details Master and use copy. Digital Library Federation, December Set up My libraries How do I set up "My libraries"?
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