1. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide

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3. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. in the clinic Constipation

4. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What are major risk factors for constipation?  Increased age  Female Gender  Race – African American  Nursing home residents  Low socioeconomic populations  Decreased physical activity  Low fluid intake, low fiber diet  Smoking – inverse association  Alcohol use – inverse association  Medications

5. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. Medications Associated with Constipation  Calcium channel blockers (nifedipine, verapamil)  Anti-depressants (tricyclic antidepressants)  Opiates  Anticholinergic agents (anticonvulsants, antipsychotics, antispasmodics)  Analgesics (opiates, NSAIDS)  Antiparkinsonian agents  Diuretics (thiazides, loop diuretics)  Cation containing agents (calcium iron, aluminum)  Antidiarrheals (oveuse) (bile acid resins)

6. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. CLINICAL BOTTOM LINE: Prevention...  Be vigilant to the risk factors associated with constipation  Risk factors for constipation  Increased age  Many co-morbid conditions  Array of medications  Decreased mobility and physical activity  Consumption of a low fiber diet  Inadequate hydration

7. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What symptoms define constipation?  Historically: < 3 bowel movements per week  But infrequency doesn’t necessarily correlate with pathophysiology or symptoms  Now: ≥ 2 of the following (for ≥ 3 months with symptom onset ≥ 6 months prior to diagnosis):  Straining during ≥ 25% defecations  Lumpy or hard stools ≥ 25% defecations  Sensation of incomplete evacuation ≥ 25% of the time  Sensation of anorectal obstruction/blockage ≥ 25% of time  Manual maneuvers to facilitate defecation ≥ 25% of the time  < 3 defecations/week

8. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What are the common subtypes of primary constipation and their distinguishing pathophysiologic features?  Normal transit constipation  Slow transit constipation  Pelvic floor dysfunction  “Combination constipation”  Slow transit constipation and pelvic floor dysfunction  Dyssynergic defecation  Functional defecatory disorders defined by alterations of events that occur during expulsion efforts  Some have slow transit + defecatory dysfunction

9. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What are the characteristic symptoms and physical exam findings?  Infrequency  Difficulty defecating  Excessive straining  Hard stools  Sensation of blockage or incomplete evacuation  “Diarrhea” or incontinence of stool (with terminal reservoir syndrome or megarectum)  Alarm signs or symptoms needing further investigation  History of rectal bleeding or anemia  Weight loss, fever  Family history of colon cancer  Age > 50 consider secondary causes of constipation

10. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1.  History  Duration of symptoms and age of onset  Temporal occurrence to other factors, diet  History of medications  Maneuvers to facilitate defecation  History of sexual abuse  Bowel and diet diary may help correlate symptoms with diet  Bristol Stool Form scale may also be helpful  Physical examination  Comprehensive abdominal examination  Comprehensive rectal examination

11. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What other conditions should clinicians consider?  Diet & lifestyle  Dehydration or inadequate fluid intake, low fiber diet  Immobility, poor bowel habits  Structural  Neoplasms (colon cancer), colonic stricture or obstruction  External compression  Neurologic  Peripheral: autonomic neuropathy, diabetes mellitus, Hirschprung disease, American trypanosomiasis  Central neurologic dysfunction: multiple sclerosis, Parkinson’s, spinal cord injury, stroke, dementia, TBI  Colonic pseudoobstruction

12. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1.  Endocrine  Hypothyroidism, hyperparathyroidism, panhypopituitarism  Diabetes mellitus, pheochromocytoma, pregnancy  Metabolic  CKD, electrolyte abnormalities  Heavy metal poisoning, porphyria  Myopathic  Myotonic dystrophy, scleroderma, amyloidosis  Psychiatric or Psychosocial  Depression, anorexia nervosa, dementia, abuse  Other  Sarcoidosis

13. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What is the role of diagnostic testing?  No need to perform tests unless history and physical exam findings suggest potential problem or include alarm sign or symptom  Target initial lab tests to the issue  CBC, basic chemistry panel including glucose, calcium, and electrolytes, thyroid function tests, urinalysis  Assess stool for occult blood  More specific testing for endocrinologic, metabolic, neurologic, or collagen vascular disorders should be based on the history and physical examination findings

14. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. When should clinicians consider obtaining tests of colonic function?  When pelvic floor dysfunction is suspected  When patients fail to respond to therapy  Tests for evaluation of constipation  Anorectal Manometry and balloon expulsion testing  Scintigraphy  Functional MRI  Defecography  Colonic marker studies  Wireless pH-pressure capsule  Colonic manometry and Barostat Testing  EMG

15. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. When should primary care clinicians consult with a gastroenterologist or surgeon for diagnosis?  If colonoscopy is required  Patients with “red flag” signs and symptoms  All patients > 50 years old with constipation  If additional functional testing are required  Motility procedures, tests of anorectal function  Know local resources for patients who may require these specialized studies and consultative opinions

16. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. CLINICAL BOTTOM LINE: Diagnosis...  Constipation is a symptom-based diagnosis  Take a comprehensive history  Perform careful physical examination  Treatment recommendation  Initiate therapy without further testing in patients without alarm signs or symptoms  After discontinuing medications that can result in constipation

17. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What is the overall approach to managing constipation?  Understand etiologies that may contribute to symptoms  Align treatment with underlying mechanism  Discontinue medications that cause constipation and can be safely stopped  Suggest a bowel habit diary and diet history to correlate dietary factors with stool consistency and timing  Determine if there is coexisting defecatory disorder  Outline the expected goals  Provide patient education about treatment rationale

18. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What is the role of dietary modification and exercise?  Increasing fiber and fluid intake is mainstay of therapy  Fluid intake alone will not improve symptoms  Fiber improves functional constipation, not IBS  Fiber requires water to work, but exact quantity unclear  Educate patients about soluble vs insoluble fiber  Soluble: oat, psyllium, certain fruits and vegetables  Insoluble: wheat bran, whole grains, dark leafy vegetables  Cramping, bloating may limit compliance: introduce slowly  Fluid intake limited with renal replacement therapy  Patients may not need fiber supplement + increased fluids if they can increase their intake of other sources of fiber

19. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. What are the mechanisms of action for constipation treatments?  Stool bulking agents  Increase fecal bulk to increase passage through colon  Stimulant laxatives  Increase colonic peristalsis in order to propel stool forward  Osmotic agents  Draw fluid into lumen leading to more rapid colonic transit  Prokinetic agents  Secretory agents

20. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. Which nonprescription medications are useful for managing constipation?  Fiber  Docusate sodium (no data for efficacy)  Castor oil (not recommended due to nutrient malabsorption)  Stimulant laxatives  Osmotic laxatives  Saline laxatives (milk of magnesia)  Magnesium citrate  Polyethylene glycol

21. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. When should clinicians consider treatment with prescription medication?  If fiber and nonprescription laxatives fail  Consider patient preference, cost, likelihood of adherence  If patients are severely constipated  No bowel movement for >1 week and not impacted  Prescription strength laxatives or nonprescription laxatives at higher than standard doses  In hospitalized or hospice patients on opiates  If traditional nonprescription remedies have failed  Methylnaltrexone or oral prescription medication

22. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. Which prescription medications are useful for managing constipation?  Osmotic agents  Lactulose  Sorbitol  Agents targeting cellular mechanisms of colonic physiology  Chloride channel-2 stimulants (lubiprostone)  Guanylate cyclase C activator (linaclotide)  Receptor antagonists (methlynaltrexone )

23. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. Is biofeedback effective in the treatment of constipation?  Studied in patients with slow transit constipation and in patients with a defecatory disorder  Most useful in patients with defecatory disorder  50% to 80% effective  Studies have shown efficacy in the elderly population

24. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. How should patients with renal insufficiency or renal failure be managed?  Many OTC and prescription laxatives are safe  Osmotic agents have limited AEs for this population  Lactulose may be a safer alternative  Several agents require dose adjustment for use with renal impairment  Avoid some medications  Sodium phosphate based compounds can cause crystalline nephropathy  Magnesium-based products, esp if creatinine >1.5 mg/dL

25. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. How should clinicians manage constipation in patients with diabetes or multiple sclerosis?  Diabetes  Focus on glycemic control  Poor glycemic control leads to worse symptoms  Multiple sclerosis  Treatment can lead to incontinence due to alteration in rectal sensation and anorectal muscle function  Pelvic floor dysfunction may also occur  Focus treatment on symptom control  Constipation may be preferable to incontinence as predominant symptom

26. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. How does management differ in the elderly?  Etiology of constipation is often multifactorial  Determine which etiologies are modifiable  Defecatory are disorders more common  Medical-functional issues that affect treatment  Important issues: ability to self-manage  Educate patient and caregivers  Laxatives may increase sense of urgency  Limitations in ambulation may mean it takes longer to get to the bathroom  Educate patients adverse events

27. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. When should clinicians consult with other providers for treatment of patients with constipation?  Gastroenterologist  Colonoscopy for unexplained iron deficiency anemia, rectal bleeding, unexplained weight loss  Motility testing for suspected pelvic floor dysfunction  Health psychologist: to help with severe symptoms  Physical therapist or biofeedback specialist: for dyssynergia  Urogynecologist: for urinary and gynecologic symptoms or pelvic floor dysfunction  Dietician: to help guide treatment

28. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. How should clinicians counsel patients about managing constipation?  Educate about etiology of constipation  Explain role of fiber, options for increasing fiber intake  Focus on reasonable goal setting for dietary changes  Provide education about use of nonprescription medications  Set clear medication adjustment guidelines  Provide guidance about when to call for additional help

29. © Copyright Annals of Internal Medicine, 2015 Ann Int Med. 162 (4): ITC4-1. CLINICAL BOTTOM LINE: Treatment...  Treatment requires attention  Lifestyle habits (toileting practice, diet, and activity)  Concurrent medications  Treatment should be individualized to underlying cause  Treat underlying etiology for enduring solution  Select nonprescription medication as a first line option  Escalate to prescription based remedies if needed