Chronic Constipation

Educational Objectives

The goal of this program is to improve the management of chronic constipation. After hearing and assimilating this program, the clinician will be better able to:

1. Review the pathophysiologic mechanisms of chronic constipation.
2. Choose appropriate diagnostic tests for patients with chronic constipation.
3. Counsel patients on evidence-based over-the-counter and prescription treatments for subtypes of constipation.

Summary

Definition: constipation lacks precise definition, but most often described as infrequent bowel movements and/or difficulty with passage of stool; symptoms may include passage of hard or lumpy stools, decreased frequency of stools, feeling of incomplete stool passage, sensation of anal blockage, or use of manual maneuvers to evacuate stool; other symptoms may include bloating, gas, cramping, or abdominal pain; some patients with constipation present with diarrhea attributable to overloaded colon, which may also cause fecal incontinence; older study data indicate that <50% of patients with constipation reported infrequent stools

Types of constipation: acute vs chronic — literature defines >3 mo duration as chronic constipation; acute more common than chronic; acute constipation may be periodic and relieved with over-the-counter (OTC) medications; primary vs secondary — primary also know as idiopathic constipation; secondary constipation due to other causes; medications — most common secondary etiology; narcotics most commonly implicated; other drugs include iron supplements, antiemetics, antihypertensives, and anti-Parkisonian agents; medical conditions — include diabetes, renal failure, hypothyroidism (rare), Parkinson disease, scleroderma, anorexia, and depression; structural causes — rare; colonoscopy rarely yields information and indicated only if other concerning symptoms present

Rome criteria: developed by international working group that periodically modifies research-standard definition of constipation; according to Rome IV criteria, patient must have ≥2 of following symptoms present for ≥25% of defecations: straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction, use of manual maneuvers to defecate, or <3 defecations/wk; loose stools should occur rarely, there should be insufficient criteria for diagnosis of irritable bowel syndrome (IBS), and symptoms should be present >3 mo; chronic constipation and IBS frequently overlap; however, patients with IBS have abdominal pain with or without constipation

Chronic idiopathic constipation (CIC): slow-transit constipation (STC) — involves slow colon activity; defecatory disorders (eg, pelvic floor dysfunction) — dyssynergic defecation occurs with uncoordinated pelvic floor activity during defecation; impaired propulsion occurs with inadequate abdominal wall or rectal activity; normally, abdominal wall creates negative pressure in addition to rectal muscle activity during defecation; normal-transit constipation (NTC) — most common subtype of CIC; 50% to 75% of patients with constipation have NTC (dyssynergic defecation most common subtype in tertiary centers)

Dyssynergic defecation: caused by uncoordinated pelvic floor skeletal muscle activity; skeletal muscles controlled by voluntary (not autonomic) nervous system; involves poor relaxation or paradoxical contraction of puborectalis (PR) and/or external anal sphincter (EAS); PR attaches at pubic symphysis and extends in U shape around rectum; PR normally remains contracted and must be voluntarily relaxed during defecation; EAS must also relax to allow anal canal to open; patients often report thin stools even after taking laxative; diagnosis — experienced physicians can diagnose with digital rectal examination; balloon expulsion test involves placement of 50-mL balloon in rectum, which patient should normally be able to expel ≤1 min; anorectal manometry involves placement of catheter to measure muscle strength during simulated defecation; electromyography less frequently done due to patient discomfort; defecography performed with barium and fluoroscopy or magnetic resonance imaging, and can image structural problems (eg, enterocele, rectocele)

Slow-transit constipation (STC): defined as delayed passage of fecal contents through colon; diagnosis requires exclusion of medications and dyssynergic defecation; diagnosis — radio-opaque marker study involves ingestion of small markers, then x-rays on days 4 and 7 with estimation of colonic transit based on markers’ location; scintigraphy — also involves radiation exposure; requires long duration and multiple images; wireless motility capsule — large nondigestible capsule, with pH sensors, that provides direct data on gastric emptying and bowel transit

Medical Therapy

Overview: lifestyle and dietary changes recommended first; dispelling misconceptions — chronic laxative use not harmful to colon; studies of ≤52 wk duration have not shown harm; patients who stop use of laxative return to baseline function but do not worsen; laxative therapy not habit-forming, again because withdrawal does not result in worsening symptoms

Bulking agents: fiber and fiber supplements consist of natural or synthetic organic polymers which can be water-soluble or -insoluble; act by increasing water retention in stool, which speeds stool transit; bran, flaxseed, rye, and other nondigestible seeds and vegetables considered insoluble; water-soluble fibers include psyllium and methycellulose (natural), calcium polycarbophil (synthetic), inulin (natural), and wheat dextran (natural); evidence — high-quality randomized controlled trials (RCTs) lacking; systematic reviews conflicting; work better for CIC than for IBS-constipation (IBS-C); psyllium has enough evidence to receive grade B recommendation; overall, bulking agents have grade C recommendation for safety and efficacy; systematic review found that psyllium improved global symptoms, increased number of defecations/wk, normalized evacuation, and reduced straining

Stool softeners: most commonly used OTC agents; docusate available as docusate sodium or calcium (speaker prefers calcium form, but calcium constipating for some); act as anionic detergents; they lower stool surface tension, which allows water to penetrate stool; evidence — few studies available, with only mixed results; speaker uses only for elderly patients; approved by Food and Drug Administration (FDA) for occasional use in constipation; advantages include few side effects, safe in pregnancy (category A), and low cost; however, minimal efficacy in CIC

Probiotics: stronger evidence exists for use in diarrhea than in constipation; because probiotics categorized as dietary supplements, FDA does not regulate, and thus quality can vary; inactive microbes do not reactivate upon ingestion and have no effect; in theory, probiotics act by speeding gut transit and increasing bowel motility; evidence — 3 RCTs suggested probiotics improved stool frequency and consistency; specific agents included Bifidobacterium lactis, Lactobacillus casei, and Escherichia coli Nissle; small crossover study found similar findings with Lactobacillus paracasei; if patient asks about probiotics, speaker recommends these 4 strains

Osmotic laxatives: polyethylene glycol (PEG) 3350 most popular; other agents include lactulose (prescription only), magnesium salts, and sorbitol; poorly absorbed and act by creating osmotic gradient that pulls water into bowel; evidence — PEG has grade A recommendation, based on 10 high-quality RCTs showing superiority over placebo; also superior to lactulose; lactulose has grade A or B recommendation (varies depending on systematic review); sorbitol and milk of magnesia (MOM) lack data, but in speaker’s clinical experience, MOM effective; limit PEG to 1 dose/day unless under physician’s care; generally well tolerated; bloating most common side effect of osmotic agents, and usually worst with lactulose and least with MOM and magnesium salts; must be ingested with ≥8 oz water

Stimulant laxatives: anthraquinones commonly used (senna, cascara); diphenylmethane laxatives include bisacodyl; stimulants activated by colonic bacteria and act by irritating colon wall (causing contractility), stimulating colonic sensory nerves, and inhibiting water absorption; cramping and pain most common side effects; have quick onset of action (usually ≤12 hr); evidence — until recently, stimulants had grade C recommendation; however, recent 4-wk study of sodium picosulfate vs placebo in Europe found it improved bowel frequency and quality of life; RCT of bisacodyl vs placebo in ≈400 patients found it increased complete and spontaneous bowel movements and improved quality of life; stimulant laxatives effective rescue agents because of quick onset; traditionally used for acute or occasional constipation, but speaker also uses in patients with STC; evidence supports safety and efficacy of chronic use; melanosis coli — harmless staining of colon wall from senna use, often identified at colonoscopy

Serotonin receptor activators: 95% of serotonin receptors located in gastrointestinal tract; prucalopride available in Europe and Canada and may be available in United States in few years; other agents have been removed from market

Chloride channel activators: mechanism of action — intestinal enterocytes contain type 2 and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels; drugs open channels, causing chloride ions to move into intestinal lumen; sodium and water then follow along ionic gradient; lubiprostone — synthetic fatty acid derived from prostaglandin; activates type 2 chloride channels; available in 8-µg and 24-µg dose; 24-µg dose approved by FDA for treatment of CIC in adults; 8-µg dose approved for IBS-C; response usually seen ≤1 wk; improves stool form, frequency, straining, and pain; generally avoid during pregnancy; side effects include nausea, abdominal pain, and headache; linaclotide — synthetic peptide; activates CFTR channel; also reduces intestinal pain; available in 145-µg dose for CIC, 290-µg dose for IBS-C, and 72-µg dose for those who have side effect of diarrhea; response usually seen ≤1 wk; improves stool form and frequency, straining, bloating, and abdominal pain; pregnancy safety unknown; diarrhea most common side effect, which can be improved by lower dose or alternate-day dosing; plecanatide — acts on CFTR receptor in pH-sensitive manner; reduces pain and constipation; available as 3-mg once-daily dose; FDA-approved for adults; pregnancy safety unknown; diarrhea most common side effect

Readings

Bharucha AE et al: Existing and emerging therapies for managing constipation and diarrhea. Curr Opin Pharmacol 2017 Dec;37:158-166; Bharucha AE et al: American Gastroenterological Association technical review on constipation. Gastroenterology 2013 Jan;144(1):218-38; Jamshed N et al: Diagnostic approach to chronic constipation in adults. Am Fam Physician 2011 Aug 1;84(3):299-306; Lembo AJ et al: Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011 Aug 11;365(6):527-36; Mounsey A et al: Management of constipation in older adults. Am Fam Physician 2015 Sep 15;92(6):500-4; Saad RJ: The wireless motility capsule: a one-stop shop for the evaluation of GI motility disorders. Curr Gastroenterol Rep 2016 Mar;18(3):14; Simren M et al: Update on Rome IV criteria for colorectal disorders: implications for clinical practice. Curr Gastroenterol Rep 2017 Apr;19(4):15; Wald A: Constipation: pathophysiology and management. Curr Opin Gastroenterol 2015 Jan 31;(1):45-9.

Disclosures

For this program, the following has been disclosed: Dr. Saad is a consultant for Allergan, Ironwood Pharmaceuticals, and Synergy Pharmaceuticals. In his lecture, Dr. Saad presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Saad was recorded at Food: The Main Course to Digestive Health, a joint presentation of the Department of Internal Medicine, University of Michigan Medical School, and Michigan Medicine, held September 22-24, 2017, in Ann Arbor, MI. For information about upcoming CME activities presented by the Department of Internal Medicine, University of Michigan Medical School, and Michigan Medicine, please visit: ocpd.med.umich.edu/cme/course-calendar. The Audio Digest Foundation thanks the speakers and the University of Michigan Medical School and Michigan Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP661502

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.