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2. What is the most common cause of constipation? A.Pelvic floor dyssynergia B.Slow transit C.Functional D.Mechanical obstruction

3. Constipation Symptom based disorder –Bloating –Hard stools –Difficult stool passage –Sensation of incomplete evacuation –Frequent straining

4. Constipation Common condition with 15% prevalence in North America and female to male ratio 2.2:1 Symptoms increase with age > 65 Primary causes –Functional (most common) include IBS-C –Defecation disorders Pelvic floor dyssynergia Excessive perineal descent Mechanical obstruction –Slow transit (least common)

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7. Initial Testing CBC TSH if there are other symptoms consistent with hypothyroidism Colonoscopy if any alarm features present - blood in stool, anemia, weight loss, or if age appropriate screening has not already been performed 7

8. Functional IBS-C –Recurrent abdominal pain at least 3 days/month during the last 3 months with onset ≥ 6 months prior –Improvement with defecation, change in stool frequency or change in stool appearance or form Chronic constipation –Straining during at least 25% of defecations –Sensation of incomplete emptying for at least 25% defecations –Sensation of anorectal obstruction for at least 25% of defecations –Need to use manual maneuvers to facilitate evacuation for at least 25% of defecations –< 3 defecations per week

9. Functional Treatment options –Fiber supplementation, exercise, healthy diet, osmotic laxative –May use stimulant laxative no more than 2-3 times per week –Rx medications Lubiprostone- chloride channel activator increases intestinal fluid secretion thereby increasing motility in the intestine Linaclotide-guanylate cyclase agonist Increases cGMP which stimulates secretion of chloride and bicarbonate which increases intestinal fluid, accelerates transit and reduces intestinal pain

10. Lubiprostone Take with food and water Chronic idiopathic constipation - 24mcg BID IBS-C (women) - 8mcg BID Opioid induced constipation (non-cancer) - 24mcg BID 10

11. Lubiprostone Adverse reactions - Nausea - Diarrhea - Headache - Dyspnea Pregnancy category C Unknown if excreted in human breast milk; not in animals - Infants should be monitored for diarrhea 11

12. Linaclotide Take on empty stomach at least 30 minutes prior to a meal Chronic idiopathic constipation - 145mcg daily IBS-C - 290mcg daily 12

13. Linaclotide Adverse reactions - Diarrhea - Abdominal pain - Flatulence Pregnancy category C Unknown if excreted in human breast milk 13

14. Pelvic Floor Dyssynergia Accounts for 1/3 of constipation in the community Likely acquired behavior disorder -Increased muscle tension from anxiety or stress -Sexual abuse is reported in 22% of women with defecation disorders Puborectalis muscles and external anal sphincter must relax Diagnosed with anorectal manometry and balloon expulsion test -evidence that pelvic floor retraining is superior to laxatives for defecatory disorders -~70% have improvement Biofeedback therapy

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17. There is currently only one prescription medication available to treat opioid induced constipation. A True B False 17

18. Opioid Induced Constipation Most common reported side effect of opioid use in 41% of patients Mu-opioid receptors - inhibition of propulsive activity of intestine and slow intestinal transit 18

19. Methylnaltrexone Bromide (Relistor) Inhibits opioids from binding to mu-receptors in GI tract Does not cross blood brain barrier - Doesn’t interfere with centrally located receptors 19

20. Methylnaltrexone Bromide Dosing Single vial dosing (12mg) and pre-filled syringe (8mg and 12mg) - Chronic non-cancer pain - 12mg SQ daily (0.6mL) - Advanced illness - weight based and every other day dosing prn - no studies past 4 months Cut dose in half for creatine clearance <30mL/min 20

21. Methylnaltrexone Bromide Category C Unsure if passes into breast milk Can cause opioid withdrawal in fetus due to immature BBB ADRs - abdominal pain, nausea, diarrhea, hyperhidrosis 21

22. Naloxegol (Movantik) Peripherally acting mu-opioid receptor antagonist; for use in chronic non-cancer pain Take on empty stomach 1 hour prior to first meal or 2 hours after 25mg PO daily; also comes in 12.5mg First BM within 6-12 hours Same ADRs as SQ injection Category C 22

23. Summary Many different causes of constipation and treatment is based on underlying cause Know when to move on from fiber and OTC medications Pelvic floor dyssynergia is extremely common in up to 1/3 of those with constipation in the community and can be treated with biofeedback

24. Summary Opioid induced constipation is managed differently than other forms of constipation Refer if any alarm features or if not comfortable moving beyond OTC medications 24

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