FOOT OFF THE BRAKES. Kerri Novak MD MSc FRCPC. Chronic Constipation: Taking the Foot off the Brakes Dr. Kerri Novak

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1 CHRONIC CONSTIPATION: TAKING THE FOOT OFF THE BRAKES Kerri Novak MD MSc FRCPC 1

2 OUTLINE Epidemiology i Quality of life Approach Therapies 2

3 DEFINING CHRONIC CONSTIPATION American College of Gastroenterology (ACG) Unsatisfactory defecation characterized by infrequent stools, difficult stool passage, or both. NORMAL BOWEL HABIT THE PASSAGE OF > 3 SPONTANEOUS COMPLETE BOWEL MOVEMENTS PER WEEK Brandt LJ, et al. Am J Gastroenterol 2005;100:S

4 SELF-REPORTED CONSTIPATION IN CANADA 27.2% No constipation Constipation seen MD Constipation not seen MD Pare et al, American Journal of Gastroenterology (11) 3130 Pinto Sanchez et al, Can J Gastroenterol (Suppl B) 11B-15B 4

5 CONSTIPATION AMONGST OLDER CANADIANS 40% 50% 60% Seniors living in the community Seniors over 80 years of age Seniors living in institutions i i Gandell et al, CMAJ (8)

6 TRUE OR FALSE? Chronic constipation occurs more frequently in women? 6

7 TRUE OR FALSE? Chronic constipation occurs more frequently in women? True False Pare et al, American Journal of Gastroenterology (11) 3130 Pinto Sanchez et al, Can J Gastroenterol (Suppl B) 11B-15B 7

8 TRUE OR FALSE? Chronic constipation impacts QOL? QOL = Quality of Life. 8

9 REDUCED PHYSICAL AND MENTAL HEALTH-RELATED QOL IN CHRONIC CONSTIPATION Health-Re elated Qualit ty of Life 60 Chronic Constipation Matched Controls p< p< PCS MCS PCS= Physical Component Score MCS= Mental Component Score True False Sun et al, Dig Dis Sci

10 CHRONIC CONSTIPATION HAS SIGNIFICANT IMPACT ON THE QUALITY OF PATIENTS LIVES Andrews et al. Presented at DDW, May 19-23,

11 CHRONIC CONSTIPATION HAS SIGNIFICANT IMPACT ON THE QUALITY OF PATIENTS LIVES 40 Impact of CC on daily activities % patient ts 20 0 Sleeping Eating Being Going out to intimate dinner Andrews et al. Presented at DDW, May 19-23,

12 RECOMMENDED APPROACH? Presenting Symptoms and Concerns What is the problem/goal/concern? GI? Is it really constipation? Alarm? Are there alarm features? Drug or Systemic Disease Diet & Lifestyle causes? Anorectal causes? Are there other associated underlying conditions? Are there patient-modifiable treatment options? Are there structural lesions? 12

13 COMMON PATIENT DESCRIPTIONS OF CONSTIPATION Physicians think: 72 < 3 BM per week Straining N = 1149 Hard or lumpy stools Incomplet e emptying Stool cannot be passed Abdominal fullness or bloating < 3 BM per week Need to press on anus Pare et al, AmJ Gastroenterol

14 BRISTOL STOOL CHART Lewis SJ, Heaton KW. Scan J Gastroenterol 1997;32(9):

15 CHRONIC IDIOPATHIC CONSTIPATION VS. IBS-C CIC IBS-C Long term ( 6 months) < 3 stools per week Stool form that is mostly hard/lumpy Difficult stool passage (straining and/or incomplete evacuation) Pare P et al. Can J Gastroenterol 2007;21(Suppl B): 3B-22B. Abdominal pain Discomfort associated with abnormal stool frequency/form tool frequency/form

16 GI: IS IT REALLY CONSTIPATION? Chronic constipation IBS-C (Constipation-predominant IBS) Food intolerance Celiac disease Eating disorder Depression / anxiety Structural GI lesion Other Pinto Sanchez et al, Can J Gastroenterol (Suppl B) 11B-15B 16

inflammatory bowel disease Nite time symptoms Tack et al.

17 Weight loss Rectal Bleeding Iron deficiency NEW onset age 50yrs with no apparent reason Significant pain FHx of colon cancer or inflammatory bowel disease Nite time symptoms Tack et al. Neurogastroenterol Motil Aug;23(8):

18 MYTH VS. FACTS In absence of alarm features what baseline labs or other tests should be done? 18

19 MYTH VS. FACTS In absence of alarm features what baseline labs or other tests should be done? CBC CBC...(AGA) Individual Assessment...Canadian Consensus Hypothyroidism...as a lone manifestation of CC is rare CC = chronic constipation AGA, Gastroenterology Pare et al, Can J Gastroenterol (Suppl B) 3B-22B 19

20 WHAT ARE THE MAJOR CLASSES OF MEDICATIONS ASSOCIATED WITH CONSTIPATION? 5-HT3 receptor antagonists Analgesics NSAIDs Opioids Anticonvulsants Antihypertensives Bile acid sequestrants Cation-containing agents Chemotherapy agents Antidepressants Antipsychotics Antiparkinsonian drugs Others AGA, Gastroenterology

21 Normal Transit Slow Transit Disordered Defecation True False 21

22 Normal Transit I go every day but the pieces are small and hard The MAJORITY of patients in primary care practice AGA, Gastroenterology Tack et al, Neurogastroenterology and Motility

23 Slow Transit I don t need to go for days at a time UNCOMMON in primary care practice ENS = enteric nervous system AGA, Gastroenterology Tack et al, Neurogastroenterology and Motility

24 Gastroenterology 2016;150:

25 25

26 Disordered Defecation I push and strain and nothing comes out AGA, Gastroenterology

27 27

28 TRUE OR FALSE? Drinking 6-10 glasses of water per day improves constipation? 28

Therapeutics 2011 33(8) 895 Pare et al, Can J Gastroenterol 2007 21(Suppl B) 3B-22B Bove et al,

29 Drinking 6-10 glasses of water per day improves constipation? True False AGA, Gastroenterology Ford et al, Alimentary Pharmacology & Therapeutics (8) 895 Pare et al, Can J Gastroenterol (Suppl B) 3B-22B Bove et al, World Journal of Gastroenterology (36) Muller-Lissner et al, Am J Gastroenterol

30 TRUE OR FALSE? Insoluble fibre helps constipation? 30

31 Insoluble fibre helps constipation? True False AGA, Gastroenterology Ford et al, Alimentary Pharmacology & Therapeutics (8)

32 Which foods contain soluble fibre? Clinical study data reporting benefit from soluble fibre in chronic idiopathic constipation (CIC) were not conducted with fruit/vegetable fibres The potential ti for benefit from fruit/vegetable t fibres is, therefore, unknown However, many patients wish to take natural fibres and, with appropriate prior discussion, it may be helpful to provide information on which foods contain soluble fibre Ford et al, Alimentary Pharmacology & Therapeutics (8)

33 TRUE OR FALSE? Eating prunes improves constipation? Ford et al, Alimentary Pharmacology & Therapeutics (8)

34 Eating prunes improves constipation? True False Attaluri et al, Aliment Pharmacol Ther

35 Laxatives Laxative Type Examples Proposed Mode of Action Potential Limitations Level of Evidence Bulking agents (insoluble & soluble fibres) Wheat bran Psyllium Methylcellulos e Calcium polycarbophil Stool bulk increases, consistency of stool improves Distension of bowel may initiate bowel activity Bloating, flatulence Impaction (not recommended in frail, immobile, palliative care) Wheat bran - Psyllium + AGA, Gastroenterology Tack et al, Neurogastroenterology and Motility Pare et al, Can J Gastroenterol (Suppl B) 3B-22B Ford et al, Alimentary Pharmacology & Therapeutics (8)

36 Laxatives Laxative Type Examples Proposed Mode of Action Softeners Docusate salts Luminal water binding Hyperosmotic Undigestable disaccharides & sugar alcohols Lactulose Sorbitol Luminal water binding; Osmotic gradient Potential Limitations Cramping Bloating, cramps, flatulence, diarrhea, taste Level of Evidence + ++ Synthetic macromolecules PEG (3350) Luminal water binding Bloating +++ Saline Mg Luminal water Cramping, diarrhea hydroxide/citrate/sul fate Sodium phosphate binding; increases fluid excretion Electrolyte imbalance (with renal disease) ++ (limited studies) Stimulants Act locally to Abdominal Diphenylmethane Bisacodyl derivatives Anthraquinones Sodium picosulfate Senna, cascara stimulate colonic motility, decrease water absorption from large intestine discomfort, cramps and diarrhea AGA, Gastroenterology Tack et al, Neurogastroenterology and Motility Pare et al, Can J Gastroenterol (Suppl B) 3B-22B +

MANAGEMENT PYRAMID GUIDE FOR PATIENTS WITH CHRONIC CONSTIPATION Set appropriate patients goals and expectations Surgery Newer Agents Osmotic laxative (e.g. MoM, lactulose, PEG) Expert assessment Rescue therapy for occasional uses: 1.

37 MANAGEMENT PYRAMID GUIDE FOR PATIENTS WITH CHRONIC CONSTIPATION Set appropriate patients goals and expectations Surgery Newer Agents Osmotic laxative (e.g. MoM, lactulose, PEG) Expert assessment Rescue therapy for occasional uses: 1. Glycerine suppository 2. Stimulant laxatives, in oral or suppository form 3. Enema Fibre supplement Eliminated removable factors Counsel on diet and physical activity Education: Acknowledge and address patient s concerns Set realistic expectations & encourage patient participation Liu, L.W. Can J Gastroenterol 2011; Vol 25(B): 26B 37

38 MODE OF ACTION OF PRUCALOPRIDE Cholinergics Cells in colonic wall Prucalopride Resolor - prucalopride, Differential Pharmacology, Jan Schuurkes, Joris De Maeyer. Some images in this presentation are adapted from Servier Medical Art and used with permission 38

39 PRUCALOPRIDE AND CHOLINERGICS: DIFFERENT MOA Prucalopride contracted relaxed Cholinergics

40 Linaclotide summary of mechanisms of action n=

OPIOID BOWEL DYSFUNCTION (OBD) Opioid receptors are widely distributed in the central and peripheral nervous system, the intestinal musculature

Opioids can affect the entire gut Dry mouth Gastroparesis Nausea, vomiting i GERD Abdominal cramping, bloating and spasm Constipation (OIC)

41 OPIOID BOWEL DYSFUNCTION (OBD) Opioid receptors are widely distributed in the central and peripheral nervous system, the intestinal musculature and other tissues. Opioids can affect the entire gut Dry mouth Gastroparesis Nausea, vomiting i GERD Abdominal cramping, bloating and spasm Constipation (OIC) Constipation is the most frequently reported ongoing symptom of OBD OIC = Opioid-Induced Constipation Peppin et al, Thomas et al, J Palliative Med (Suppl 1) S1-S

TARGETED THERAPIES FOR OIC Opioid idantagonists t Peripherally restricted Methylnaltrexone bromide Limited systemic bioavailability Oral naloxone* Oral Naloxegol (Peripherally Acting Mu-Opioid

42 TARGETED THERAPIES FOR OIC Opioid idantagonists t Peripherally restricted Methylnaltrexone bromide Limited systemic bioavailability Oral naloxone* Oral Naloxegol (Peripherally Acting Mu-Opioid Receptor Antagonis) Oxycodone Hydrochloride/Naloxone Hydrochloride Controlled Release Tablets *narrow therapeutic window with reversal of analgesia in some patients (with >12 mg orally of iv IR formulation) RELISTOR is indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care. When response to laxatives has been insufficient, RELISTOR should be used as an add-on therapy to induce a prompt bowel movement. Targin is a controlled release tablet having a dual therapeutic effect. The oxycodone component in Targin is indicated for the relief of moderate to severe pain in adults who require continuous around-the-clock opioid analgesia for several days or more. The naloxone component in Targin is indicated for the relief of OIC; All marks above are the property of their respective owners 42

43 TAKE HOME 1. Most cases of constipation in primary care will be normal transit, with or without abdominal discomfort (CIC or IBS-C) 2. This is a benign condition that does NOT increase the risk of colon cancer 3. Lifestyle and medical therapies are management mainstays 43

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45 Questions 45

Elderly Man With Chronic Constipation

Elderly Man With Chronic Constipation Linda Nguyen, MD Director, Neurogastroenterology and Motility Clinical Assistant Professor Stanford University Overview Normal bowel function Defining Constipation: