Chronic constipation - an evidenced based approach

2. Chronic constipation - an evidenced based approach Robert A. Baldor, MD, FAAFP Professor, Family Medicine & Community Health UMass Medical School

3. Learning Objectives by the end of the session, you will have a clear understanding of the basic pathophysiology related to chronic constipation …and develop an evidenced based approach for the primary care diagnosis and treatment of these chronic problems.

4. Mrs Z. A 34-year-old white female who complains of constipation; she hasn’t discussed it in the past as “it’s embarrassing,” but states that she has been constipated her entire life and has tried a variety of OTC products without much relief. She further reports that she is very active, runs 4 days a week, that she always has a bottle of water with her and tries to eat salads regularly…..

5. History Character of the problem Consistency Frequency Straining, bloating Diarrhea Medications

6. Mrs. Z Doesn’t have much discomfort, but has to strain and has hard stools along with blood occasionally on TP – she tends to go about twice a week She will occasionally have diarrhea – but it seems related to something she had eaten Takes Tums for her ‘bones’

7. Constipation No Clear Definition A group of syndromes with similar findings

8. Am College of Gastroenterology … Unsatisfactory defecation, characterized by infrequent stools and/or difficult stool passage Brandt 2005

9. Pathophysiology… As food leaves stomach, gastroileal reflex relaxes the ileocecal valve and digested food (chyme) enters the colon Peristaltic contractions move chyme through the colon Na+ actively absorbed - water follows because of the generated osmotic gradient

10. Normal Colonic Transit Time A meal reaches the ileo-cecal valve in 4 hours …the sigmoid colon 12hours later … then slows to the anus. Plastic pellets with a meal → 70% recovered in 3 days; remainder in a week!

11. Defecation Food distends the stomach, initiating the gastro-colic reflex causing rectal contractions & a desire to go! ‘Urge to defecate’ occurs as rectal pressures ↑ Defecation reflexes can be inhibited by voluntarily contracting the external sphincter or facilitated by straining Pelvic floor/anal sphincter dysfunction interfere with normal defecation

12. Most with primary constipation suffer from which one of the following? Slow colonic transit time Pelvic floor/anal sphincter dysfunction Functional – normal transit time and sphincter function

13. Most with primary constipation suffer from which one of the following? Slow colonic transit time Pelvic floor/anal sphincter dysfunction Functional – normal transit time and sphincter function

14. Secondary Constipation Endocrine dysfunction (DM, hypothyroid) Metabolic disorder (↑ Ca,↓ K) Mechanical (obstruction, rectocele) Pregnancy Neurologic disorders (Hirschsprung’s, multiple sclerosis, spinal cord injuries)

15. Medication Effect Anti-cholinergic effects Antidepressants Narcotics Antipsychotics Calcium channel blockers Antacids (calcium, aluminum) Mrs. Z taking Tums (ca carbonate) for osteoporosis - ca phosphate (Posture) and ca citrate (Citracal) less constipating.

16. IBS ? Rome III Criteria Symptoms at least 3 days/month of recurrent abdominal pain or discomfort associated with hard constipated stools interrupted by brief episodes of diarrhea … Drossman Gastroenterology. 2006

17. IBS Treatment Multiple RCTs with inconsistent results – best evidence for treating IBS-C: Bulking agents Psychotropic agents DARE review 2001

18. Red flags Onset after age of 50 Hematochezia/melena Unintentional weight loss Anemia Neurological defects

19. Physical Exam Digital rectal examination Stool character Pain, anal tone Masses, fissures, hemorrhoids, Abdominal/gynecological exam Masses, pain Neurological exam

20. Treatment – Behavioral Toileting program to take advantage of natural reflexes Obey the urge Gastro-colic Defecation reflex

21. Medications - Laxatives Bulking agents Stool softeners Osmotic agents Stimulants Lubricants Other

22. Bulking Agents at the Grocery Store… Vegetables Fruits Whole grain foods Bran (hard outer layer of cereal grains)* Bloating and gas can be problematic Gradually increase intake to 25 grams/day Less fermentable fiber like wheat bran tends to be better tolerated * Limited evidence for effectiveness

24. Bulking Agents at the Pharmacy… Moderate evidence Psyllium (Metamucil 2.5gms fiber/dose) Limited evidence Bran methycellulose (Citrucel 2gms fiber/dose) Polycarbophil (Fibercon) Fiber needs to be accompanied by adequate amounts of liquid to be useful - 8oz/2-3gms of added fiber!

25. Stool Softeners – Limited Evidence Contain docusate (Colace), an anionic detergent with hydrophilic and hydrophobic ends that improves the ability of water to mix with and soften the stool Helpful to soften stools to make defecation easier (post-op, childbirth) Helpful for hemorrhoids or anal fissures ↑ dose if no effect is seen after a week 40-400mg daily QD-QID

26. Stimulants (Irritants) Irritate bowel, causing muscle contractions often in combination with ducosate – work in 8-12 hrs (try qhs, increase to BID) Senna/ducosate (Senokot-S, Ex-lax - max 4/d) Bisacodyl/ducosate (Dulcolax, Correctol- max 30mg/d) Casanthranol/ducosate (Peri-colace – max 2/d)

27. Stimulant Suppositories … Contain bisacodyl/ducosate (Dulcolax) Glycerin suppositories also believed to have their effect by irritating the rectum Insertion of the suppository into the rectum may itself stimulate a bowel movement

28. Osmotic Laxatives Polyethylene glycol - PEG (good evidence) 17 grams daily Saccharines – lactulose (moderate evidence) flatulence, bloating, cramping 15 - 120 ml qhs Sorbitol (effective as lactulose in elderly men*) less bloating than lactulose 15 - 120 ml qhs Magnesium salts (MOM) avoid in renal insufficiency, best for acute treatment * Lederle. ACP Journal Club, 1991.

29. A Closer Look at Polyethylene Glycol - good evidence for use PEG: Large, chemically inert polymer, with substantial osmotic activity Bowel flora unable to metabolize Pulls water into colon to soften and increases fecal bulk (takes 2-4 days to work) First used in a balanced electrolyte solution for colon cleansing (Golytely) PEG 3350 (Miralax) or with electrolytes (Movical)

30. Lubricant Laxatives Contain mineral oil (15-45 ml/day) Short-term use only Binds fat-soluble vitamins May decrease absorption of some drugs Avoid lubricants in those at risk for aspiration (lipid pneumonia)

31. Lubiprostone (Amitiza) Selective Chloride channel activator ↑ secretion of Cl-ions into small bowel; Na+ and water follow, resulting in a softer, bulkier stool 24 mcgs BID Nausea is common (32%) Avoid use in pregnancy, breast-feeding

32. Methylnaltrexone (Relistor) • Methyl group reduces lipidophilic properties of the opioid antagonist naltrexone - ↓ ability to cross blood-brain barrier • Peripherally Acting Mu-Opioid Receptor (PAM-OR) antagonist • Indicated for palliative care • For short-term use (< 4months) • Side effects - abdominal pain and flatulence

33. Other, Non-FDA Approved Agents, Act to Decrease Transit Time Misoprostol (Cytotec 100-200mcg QID) a prostaglandin increases colonic motility1 Colchicine (0.6mg qd - tid) neurogenic stimulation ↑ colonic motility 2 1.Roarty. Alimen pharm & Therapeutics. 1997 2. Verne. Am J. Gastroenterology. 2003, Frame J ABFP, 1998

34. A Practical Approach… R/O treatable secondary causes.. Am Gastroenterological Assn (AGA) guidelines: CBC, Glucose, TSH, calcium, creatinine Sigmoid/colonoscopy if red flags are present.

35. Address Immediate Concerns Bloating/discomfort/straining Osmotic agent like PEG Post-op, childbirth, hemorrhoids, fissures Stool softener to make defecation easier Stimulants and suppositories acutely Manual disimpaction as needed then approach the chronic condition….

36. Start with Lifestyle Changes … Exercise, increase fluids and fiber to 25 grams/day over a period of 6 weeks.* Fiber must be accompanied by sufficient fluid Initial approach – fruits and vegetables Add commercial bulking agents Obey the ‘Urge’! For children trial of rice vs cow’s milk * Uncontrolled studies support fiber for normal transient constipation. Am J Gastroenterol. 1999; G Nutr 4/2010

37. If No Improvement… Add osmotic laxative adjust dose slowly until stools are soft take several days to work caution if CHF or renal insufficiency Add stimulant laxatives Lubiprostone

38. Trial of Other Agents… Misoprostol (Cytotec) Colchicine Refractory to empiric approach .…

39. Pursue Diagnostic Evaluation Colonoscopy if not indicated sooner …. Barium enema for obstruction/megacolon Radiopaque Sitz-Markers to measure transit time markers ingested, KUB in 5 days retention >20% markers indicates slow transit markers seen exclusively in distal colon/rectum suggests pelvic floor dysfunction

40. Referral to evaluate defecation…. Balloon expulsion Defecography using a barium paste. Anorectal manometry with a rectal catheter Biofeedback with artificial silicon stool Surgery rarely indicated Enck. Dig Dis Sci. 1993

41. Summary…. Constipation - unsatisfactory defecation, with infrequent stools, difficult stool passage or both Functional constipation (normal transit time and sphincter function) seen most often Work-up is necessary in the presence of red flags onset >50 yrs; hematochezia/melena; unintentional weight loss; anemia; neurological defects Best evidence for effectiveness is for osmotic agents

42. Long-term Laxative Concerns… No evidence for addiction No evidence for tolerance No evidence for dependence No evidence for harm from stimulant use, melanosis coli may develop, but it is a benign condition Muller-Lissner. Am J Gastroenterology. 2005

43. The End!