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Sunday, March 25 - New Therapies for Chronic Constipation

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New Therapies for Chronic Constipation
0006-0000-18-009-L01-P | .1 CEUs |
Deepti Vyas, PharmD

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Sunday, March 25 - New Therapies for Chronic Constipation

  1. 1. NE W T HE RAP IES F O R C HRO NIC C O NS TIPATIO N D E E P T I V YA S P H A R M D A S S O C I AT E P R O F E S S O R U N I V E R S I T Y O F T H E PAC I F I CNo conflict of interest to report.
  2. 2. http://www.gibbleguts.com/laxative-choices.html
  3. 3. BY THE END OF THIS PRESENTATION, THE ATTENDEE SHOULD BE ABLE TO…. • Define chronic constipation • Describe criteria for diagnosing a patient with chronic constipation • Describe the clinical presentation of chronic constipation • Identify appropriate therapeutic options for adults with chronic constipation based on the etiology • Describe new therapeutic options including efficacy and safety data • Outline the pharmacist role in managing patients with chronic constipation
  4. 4. DEFINITION OF CHRONIC IDIOPATHIC CONSTIPATION • Per the American College of Gastroenterology, constipation is “a symptom- based disorder defined as unsatisfactory defecation and is characterized by infrequent stools, difficult stool passage, or both. Chronic idiopathic constipation (CIC) or functional constipation is defined as the presence of these symptoms for at least 3 months.” • Difficult stool passage is characterized by: – straining – a sense of difficulty passing stool – feeling of incomplete evacuation – hard / lumpy stools – prolonged time to stool – need for manual or digital maneuvers to defecate.Ford AC, Moayyedi P, Lacy BE, et al; Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(suppl 1):S2-S26. With symptoms noted for 6 months or longer
  5. 5. EPIDEMIOLOGY • The overall prevalence of chronic constipation is about 14% among the general public. • Constipation is more common in females, in older subjects, and those of lower socioeconomic status • Chronic constipation has also been linked to impaired quality of life, especially in older patients. • Constipation accounts for 8 million physician visits each year. 1. Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(9):1582. 2. Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99(4):750. 3. Sandler RS, Jordan MC, Shelton BJ. Demographic and dietary determinants of constipation in the US population. Am J Public Health 1990; 80:185. 4. Sonnenberg A, Koch TR. Physician visits in the United States for constipation: 1958 to 1986. Dig Dis Sci 1989; 34:606.
  6. 6. ROME IV CRITERIA FOR CHRONIC IDIOPATHIC CONSTIPATION (1) Must include two or more of the following: – Straining during more than 25% of defecations – Lumpy or hard stools (Bristol Stool Scale Form 1-2) in more than 25% of defecations – Sensation of incomplete evacuation for more than 25% of defecations – Sensation of anorectal obstruction/blockage for more than 25% of defecations – Manual maneuvers to facilitate more than 25% of defecations – Fewer than 3 spontaneous bowel (2) No reports of loose stools unless due to laxatives use AND (3) There are insufficient criteria for irritable bowel syndrome. Mearin F, et al. Bowel Disorders. Gastroenterology. 2016;Volume 150, Issue 6, Pages 1393–1407.e5 The ROME criteria which was updated in 2016, requires the presence of the following for 3 months or longer (with symptom onset at least six months prior to diagnosis).
  7. 7. ETIOLOGY • Constipation may be conceptualized as a disordered movement of stool through the colon or anorectum. • Slowing or disordered colonic time can be caused by a medical condition or due to a medication side effect. • Other causes include either normal colonic transit, slow transit constipation, or dysynergic defecation.
  8. 8. CAUSES OF CONSTIPATION Neurogenic disorders Non-neurogenic disorders Peripheral Hypothyroidism Diabetes mellitus Hypokalemia Autonomic neuropathy Anorexia nervosa Intestinal pseudoobstruction Pregnancy Central Systemic sclerosis Multiple sclerosis Myotonic dystrophy Spinal cord injury Parkinson disease Idiopathic constipation Irritable bowel syndrome Normal colonic transit Drugs Slow transit constipation Dyssynergic defecation www.uptodate.com
  9. 9. DRUG-INDUCED CAUSES OF CONSTIPATION • Analgesics – PG inhibitors – Opiates • Anticholinergics – Antihistamines – Antiparkinsonian agents – Phenothiazines – TCA • Antacids with Al or Ca • Barium sulfate • CCB’s • Clonidine • Diuretics (non K sparing) • Ganglionic blockers • Iron preps. • Muscle blockers • NSAIDs • Polystyrene sodium sulfonate
  10. 10. EVALUATION • For most cases, a complete physical examination or imaging is not required as long as it is established that the constipation: – is not accompanied by signs of significant GI disease (i.e., alarm symptoms such as rectal bleeding, unexplained weight loss, or anemia) – does not cause severe discomfort. • Patients with alarm symptoms, with a family history of colon cancer, or those >50 years old with new symptoms may need further diagnostic evaluation. • A digital rectal exam is useful in identifying any underlying pathology that could be contributing to constipation such as hemorrhoids, high anal sphincter tone, etc. • In most cases, a careful history and limited physical is likely adequate.
  11. 11. GENERAL APPROACH TO TREATMENT • Patient education can be an important component of managing a patient with CIC. • Counsel patients to : – Increase the amount of fiber consumed daily. The recommended amount of dietary fiber is 20 to 35 g/day. – Patients may also add raw bran (two to six tablespoons with each meal). – Incorporate an exercise regimen. – Increase fluid intake. – Adjust bowel habits so that a regular and adequate time is made to respond to the urge to defecate. OBEY THE URGE. • Offer a step-wise approach to treatment
  12. 12. STEP-WISE APPROACH TO THERAPY • Treat specific cause • Stepwise therapy: – Dietary modification to increase fiber ± supplementation (bulk forming agents) – Add an osmotic laxative if no relief; trial 2-4 weeks – May add an stimulant laxative (e.g bisacodyl) prn – Add an intestinal secretogogue. • Lubiprostone, linaclotide or plecanatide. • If one fails, try another Ford AC, Moayyedi P, Lacy BE, et al; Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(suppl 1):S2-S26.
  13. 13. FIBER • Raw bran is generally 40% fiber. • Bulk-forming agents such as psyllium hydrophilic colloids, methylcellulose, or polycarbophil, are similar to dietary fiber. • A trial of high-fiber diet should be continued for at least 1 month. • Most patients begin to notice effects on bowel function 3 to 5 days after beginning a high-fiber diet • Bulk-forming laxatives should be taken with plenty of fluid to avoid choking. • Patients should be warned that consuming large amounts of fiber can cause abdominal bloating or flatulence – Psyllium husk can undergo bacterial fermentation which produces gas and bloating. – Semisynthetic bulking agents such as calcium polycarbophil and methylcellulose are less likely to ferment.
  14. 14. BULK-FORMING LAXATIVES Psyllium Up to 1 tablespoon (≅3.5 grams fiber) 3 times per day 12 to 72 h Methylcellulose Up to 1 tablespoon (≅2 grams fiber) or 4 caplets (500 mg fiber per caplet) 3 times per day 12 to 72 h Polycarbophil 2 to 4 tabs (500 mg fiber per tab) per day 24 to 48 h Wheat dextrin 1 to 3 caplets (1 gram fiber per caplet) or 2 teaspoonsful (1.5 gram fiber per teaspoon) up to 3 times per daily 24 to 48 h Wald A. Management of chronic constipation in adults. Accessed online at https://www.uptodate.com
  15. 15. OSMOTIC AGENTS • Polyethylene glycol* • Lactulose* • Sorbitol • Glycerin • Magnesium salts * Have evidence supporting use in CIC
  16. 16. POLYETHYLENE GLYCOL (PEG) • FDA-approved for treatment of constipation at low doses and is expected to produce a bowel movement in 1 to 3 days. • Dosing: 17 g of powder dissolved in 8 oz of water once daily and titrate up or down (to a maximum of 34 g daily). • ADRs: nausea, vomiting, flatulence, and abdominal cramping. • Five studies compared PEG with placebo; four reported data in 573 patients with the NNT of 3 (95 % CI 2 – 4). These trials were considered of high quality. 1. Corazziari E , Badiali D , Habib FI et al. Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation. Dig Dis Sci 1996 ; 41 : 1636 – 42 . 2. Corazziari E , Badiali D , Bazzocchi G et al. Long term efficacy, safety, and tolerability of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut 2000 ; 46 : 522 – 6 . 3. DiPalma JA , DeRidder PH , Orlando RC e t al. A randomized, placebo controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative . Am J Gastroenterol 2000 ; 95 : 446 – 50 . 4. DiPalma JA , Cleveland MV , McGowan J et al. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation . Am J Gastroenterol 2007 ; 102 : 1436 – 41 . 5. Baldonedo YC , Lugo E , Uzcategui AA et al. Evaluation and use of polyethylene glycol in constipated patients] . G E N 1991 ; 45 : 294 – 7.
  17. 17. LACTULOSE • Mechanism of action: Lactulose is a nonabsorbable disaccharide that is used orally or rectally. Lactulose increases stool frequency and consistency in patients with chronic constipation. • It may be justified as an alternative in patients with an inadequate response to increased dietary fiber and bulking agents. However, head-to-head studies suggest that lactulose is slightly less effective than PEG. • Dosing: Oral: 10 to 20 g (15 to 30 mL) daily; may increase to 40 g (60 mL) daily • ADRs: flatulence, nausea, and abdominal bloating. • Studies that evaluated lactulose showed significant improvement with lactulose versus placebo, with the NNT of 4 (95 % CI 2 – 7). However, these studies were not considered high in quality. 1. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus Polyethylene Glycol for Chronic Constipation. Cochrane Database Syst Rev. 2010; 2. Wesselius-De Casparis A , e t al. Treatment of chronic constipation with lactulose syrup: results of a double blind study . Gut 1968 ; 9:84 – 6 . 3. Sander JF . Lactulose syrup assessed in a double-blind study in elderly constipated patients . J Am Geriatr Soc 1978 ; 26 : 236 – 9
  18. 18. STIMULANT LAXATIVES • Bisacodyl • Senna • Mechanism of action: Stimulate the mucosal nerve plexus of the colon. May also increase intestinal fluid secretion. • Cause a bowel movement within 6 to 12 hours of use. • ADRs: May cause severe abdominal cramping and electrolyte imbalances
  19. 19. BISACODYL • Reserved for intermittent use (every few weeks) for immediate relief of constipation. • It may be administered orally or as a suppository. • Dosing: 5 to 15 mg po once daily or 10mg rectally once daily • If suppositories are used, administering them 30 minutes after breakfast may synchronize the drug effects with the regular gastrocolonic response. • May cause severe abdominal cramping with chronic use. • No compelling evidence that chronic use causes structural or functional impairment of the colon, or that it increases the risk for colorectal cancer or other tumors. Kamm MA , Mueller-Lissner S , e t al. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation . Clin Gastroenterol Hepatol 2011;9:577–83 .
  20. 20. SENNA • Dosing: Usually 17.2mg once a day (Max 34.4mg per day). • Once daily dosing should be given at night. Generally recommended for intermittent use when needed for immediate relief. • No compelling evidence that chronic use causes structural or functional impairment of the colon, or that it increases the risk for colorectal cancer or other tumors.
  21. 21. EVIDENCE FOR TRADITIONAL THERAPIES • Methods: A systematic review of studies that were randomized, conducted on adult subjects to measure the efficacy of commonly used agents for chronic constipation. • Results: Data supporting the use of polyethylene glycol (PEG) is of high quality while data supporting the use of psyllium and lactulose is of moderate quality. • Data supporting the use of other traditional agents including senna, bisacodyl, and stool softeners is scarce and of low quality. Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol. 2005;100(4):936.
  22. 22. INTESTINAL SECRETOGOGUES Lubiprostone Linaclotide Plecanatide 2006 2012 2017
  23. 23. Plecanatide Nature Reviews Disease Primers. 2016;volume 2: 16014
  24. 24. LUBIPROSTONE (AMITIZA) • Mechanism of action: Is a chloride channel activator that acts locally in the gut to open chloride channels on the GI luminal epithelium, which, in turn, stimulates chloride-rich fluid secretion into the intestinal lumen. Increased intraluminal fluid secretion helps to soften stool and accelerates GI transit time. • Dosing: 24 mcg capsule BID with food. • ADRs: Headache, nausea, diarrhea • Contraindications: Known or suspected mechanical gastrointestinal obstruction • Cost: $445.32/month 1. Johanson JF, Ueno R. Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo- controlled, dose-ranging study to evaluate efficacy and safety. Aliment Pharmacol Ther. 2007;25(11):1351 2. Lang L. The Food and Drug Administration approves lubiprostone for irritable bowel syndrome with constipation. Gastroenterology. 2008;135(1):7. Epub 2008 Jun 9.
  25. 25. • Design: Meta-analysis of clinical trials on the use of lubiprostone in chronic idiopathic constipation and irritable bowel syndrome. • Primary endpoints: Frequency of spontaneous bowel movements (SBM), severity of constipation, consistency of stools, degree of abdominal pain/discomfort, degree of straining, and abdominal bloating. • Results: Data from 9 trials was reviewed.1468 patients (63.6%) in the lubiprostone group and 841 (36.4%) in the placebo group were analyzed. Lubiprostone significantly improved the severity of constipation, stool consistency, abdominal pain, degree of straining, and abdominal bloating at 1 week (P≤.03) and 1 month (P≤.004), except for abdominal pain at 1 month (P=.21). At 3 months, only abdominal bloating (P=.03) was significantly improved in the lubiprostone arm. • Adverse effects: nausea, vomiting, and diarrhea were common (incidence rate- 2.4%-75%). Li F, et al. Lubiprostone Is Effective in the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome. A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Mayo Clinic Proceedings. 2016; Volume 91(4): Pages 456–468 LUBIPROSTONE
  26. 26. LUBIPROSTONE, A LOCALLY ACTING CHLORIDE CHANNEL ACTIVATOR, IN AD ULT PATIENTS WITH CHRONIC CONSTIPATION: A DOUBLE‐BLIND, PLACEBO‐CONTROLLED, DOSE‐RANGING STUDY TO EVALUATE EFFICACY AND SAFETY Alimentary Pharmacology & Therapeutics. 2007; Volume 25 (11); pages 1351-1361
  27. 27. LUBIPROSTONE, A LOCALLY ACTING CHLORIDE CHANNEL ACTIVATOR, IN AD ULT PATIENTS WITH CHRONIC CONSTIPATION: A DOUBLE ‐BLIND, PLACEBO‐CONTROLLED, DOSE‐RANGING STUDY TO EVALUATE EFFICACY AND SAFETY Alimentary Pharmacology & Therapeutics. 2007; Volume 25 (11); pages 1351-1361 Patients experiencing a spontaneous bowel movement (SBM) within 24h of initial dose om = 24 mcg o.m., bd = 24 mcg b.d., tds = 24 mcg t.d.s
  28. 28. LINACLOTIDE (LINZESS) • Is a minimally absorbed peptide agonist of the guanylate cyclase-C receptor that stimulates intestinal fluid secretion and transit. • Approved for the treatment of CIC at a dose of 145μg daily. Lower doses (72μg) may be used in select patients. • Administer at least 30 minutes before the first meal of the day on an empty stomach. • ADRs: – Diarrhea (16-22%) • Diarrhea may occur after administration with a high-fat breakfast. – Abdominal pain – Flatulence • Contraindications: Known or suspected mechanical gastrointestinal obstruction • Cost: 72μg or 145μg dose: $464.47/month Lembo AJ, Kurtz CB, MacDougall JE et al. Efficacy of linaclotide in patients with chronic constipation. Gastroenterol 2010;138:886–895.
  29. 29. LINACLOTIDE • Design: Two randomized, 12-week, multicenter, double-blind, parallel-group, placebo- controlled, dual-dose trials were conducted on1276 patients with chronic constipation. Patients received placebo or linaclotide 145 μg or 290 μg. • Primary efficacy end points: 3 or more complete spontaneous bowel movements (CSBMs) per week and an increase of one or more CSBMs from baseline during at least 9 of the 12 weeks. Lembo AJ, et al. Two randomized trials of linaclotide for chronic constipation. New Engl J Med. 2011;365(6):527
  30. 30. LINACLOTIDE Two randomized trials of linaclotide for chronic constipation. Lembo AJ, et al. New Engl J Med. 2011;365(6):527 Primary Efficacy End Point in the Linaclotide and Placebo Groups in Each Trial. The primary efficacy end point was defined as a weekly frequency of three or more complete spontaneous bowel movements (CSBMs) and an increase of one or more CSBMs from baseline for at least 9 weeks of the 12-week treatment period. *P≤0.001, vs. placebo; **P≤0.01, vs. placebo. ADRs: In the linaclotide arm, diarrhea, occurred in 4.2% of patients.
  31. 31. Mean Number of Weekly Complete Spontaneous Bowel Movements (CSBMs) Two randomized trials of linaclotide for chronic constipation. Lembo AJ, et al. New Engl J Med. 2011;365(6):527 LINACLOTIDE
  32. 32. LINACLOTIDE 72MCG VERSUS THE 145 MCG DOSE • Design: Double-blind, placebo-controlled trial randomized patients with CIC to once- daily linaclotide 72 μg or 145 μg, or placebo for 12 weeks. • Primary endpoints: 12-week complete spontaneous bowel movement (CSBM) overall responder, required patients to have ≥3 CSBMs and an increase of ≥1 CSBM per week from baseline in the same week for at least 9 of the 12 weeks studied. Schoenfeld P et al. Low-Dose Linaclotide (72 μg) for Chronic Idiopathic Constipation: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Am J Gastroenterol. 2018 Jan; 113(1): 105–114.
  33. 33. Percent of patients who were 12-week CSBM overall responders (primary endpoint) and sustained responders (additional endpoint). †Multiple comparisons procedure (MCP). Schoenfeld P et al. Low-Dose Linaclotide (72 μg) for Chronic Idiopathic Constipation: A 12-Week, Randomized, Double-Blind, Placebo- Controlled Trial. Am J Gastroenterol. 2018 Jan; 113(1): 105–114. ADRs: Diarrhea resulted in discontinuation of 0, 2.4%, and 3.2% of patients in the placebo, linaclotide 72-μg, and linaclotide 145-μg groups, respectively. LINACLOTIDE
  34. 34. Weekly mean bowel and abdominal symptom scores over the 12-week Schoenfeld P et al. Low-Dose Linaclotide (72 μg) for Chronic Idiopathic Constipation: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Am J Gastroenterol. 2018 Jan; 113(1): 105–114. LINACLOTIDE
  35. 35. PLECANATIDE (TRULANCE ) • Mechanism of action: A synthetic analog of uroguanylin, which is an endogenous guanylate cyclase-C receptor agonist. Plecanatide binds to guanylate cyclase-C on the luminal surface of the intestinal epithelium, thereby increasing cyclic guanosine monophosphate (cGMP). This then activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased secretion of chloride. This ultimately accelerates intestinal transit. • Dosing: Oral: 3 mg once daily • ADRs: – Diarrhea (5%) – abdominal distension (<2%) – abdominal tenderness (<2%) – flatulence (<2%) • Contraindications: Known or suspected mechanical gastrointestinal obstruction • Cost: $466.16 per month 1. Krause R, Foehl H, Koltun W, et al. Sa1444 effect of plecanatide on stool consistency in the treatment of chronic idiopathic constipation (CIC): results from two phase III studies. Gastroenterology. 2016;150:S317 2. Nualart M, Morgan W, Berenguer R, et al . Sa1443 effect of plecanatide on patient assessments in chronic idiopathic constipation (CIC): results from two phases III studies. Gastroenterology. 2016;150:S317.
  36. 36. PLECANATIDE • Design: The efficacy of plecanatide for treatment of CIC was evaluated in a12-week, randomized, double-blind trial. • Methods: Compared plecanatide 3 mg or 6mg once daily with placebo. • Primary endpoint: Percentage of patients who were durable overall complete spontaneous bowel movement (CSBM) responders over the 12-week treatment period. • Results: 1,394 patients participated in the study. Miner PB, et al. A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation. Am J Gastroenterol. 2017 Apr;112(4):613-621.
  37. 37. PLECANATIDE (a) Percentage of patients in each treatment group assessed as a durable overall complete spontaneous bowel movement (CSBM) responder in the intention-to-treat (ITT) population, the primary efficacy endpoint. Durable overall CSBM responders were defined as patients who fulfilled both ≥3 CSBMs per week and an increase of ≥1 CSBM from baseline, in the same week, for ≥9 of the 12 treatment weeks, including ≥3 of the last 4 weeks of treatment. Error bars represent 95% confidence intervals. (b) Weekly evolution of the percentage of CSBM responders in the ITT population. Values are LS means; bars represent 95% confidence intervals. *P=0.001, **P=0.003, †P=0.005, ‡P=0.011 vs. placebo. Miner PB, et al. A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation. Am J Gastroenterol. 2017 Apr;112(4):613-621. ADRs: Diarrhea, occurred in 1.3% (placebo), 5.9% (3 mg) and 5.7% (6 mg) of patients.
  38. 38. PLECANATIDE (a) Changes from baseline in weekly complete spontaneous bowel movement (CSBM) frequency. Values are least squares (LS) mean; bars represent s.e. *P<0.001 vs. placebo. (b) Changes from baseline in mean weekly spontaneous bowel movement (SBM) frequency. Values are LS mean; bars represent s.e. *P<0.001 vs. placebo. (c) Percentage of patients experiencing a CSBM or SBM within 24 h after the first dose of study medication. *P<0.001 vs. placebo. Miner PB, et al. A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation. Am J Gastroenterol. 2017 Apr;112(4):613-621.
  39. 39. SUMMARY OF RECOMMENDATIONS Drug Class Recommendation Quality of Evidence Number needed to treat Fiber Strong Low 2 Polyethylene glycol Strong High 3 Lactulose Strong Low 4 Bisacodyl Strong Moderate 3 Linaclotide Strong High 6 Lubiprostone Strong High 4 Plecanatide NA High Ford AC, Moayyedi P, Lacy BE, et al; Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(suppl 1):S2-S26.
  40. 40. WHEN TO REFER.. Presence of alarm symptoms: • Hematochezia • Positive fecal occult blood test (FOBT) • Unintentional weight loss of ≥10 pounds • A family history of colon cancer • A family history of inflammatory bowel disease • Anemia • Acute onset of symptoms in elderly patients
  41. 41. TEACHING TOOL Try another secretogogue Patient diagnosed with chronic idiopathic constipation Increase dietary fiber intake and/or add bulking agent Add PEG +/- a stimulant (PRN) Add an intestinal secretogogue Improvement Continue Regimen. Monitor periodically.Improvement Improvement Stimulant Laxatives: • Senna • Bisacodyl Intestinal Secretogogues: • Linaclotide • Lubiprostone • Plecanatide Wald A. Constipation Advances in Diagnosis and Treatment JAMA January 12, 2016 Volume 315, Number 2 Bulking Agents: • Psyllium • Methylcellulose • Polycarbophil • Wheat Dextrin
  42. 42. Thank you!

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