CHRONIC CONSTIPATION: TAKING THE FOOT OFF THE BRAKES Kerri Novak MD MSc FRCPC www.seacourses.com 1
OUTLINE Epidemiology i Quality of life Approach Therapies www.seacourses.com 2
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:S5 www.seacourses.com 3 3
SELF-REPORTED CONSTIPATION IN CANADA 27.2% 18.11 9.1 72.7 No constipation Constipation seen MD Constipation not seen MD Pare et al, American Journal of Gastroenterology 2001 96(11) 3130 Pinto Sanchez et al, Can J Gastroenterol 2011 25(Suppl B) 11B-15B www.seacourses.com 4
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 2013 185(8) 663-670 www.seacourses.com 5
TRUE OR FALSE? Chronic constipation occurs more frequently in women? www.seacourses.com 6
TRUE OR FALSE? Chronic constipation occurs more frequently in women? True False Pare et al, American Journal of Gastroenterology 2001 96(11) 3130 Pinto Sanchez et al, Can J Gastroenterol 2011 25(Suppl B) 11B-15B www.seacourses.com 7
TRUE OR FALSE? Chronic constipation impacts QOL? QOL = Quality of Life. www.seacourses.com 8
REDUCED PHYSICAL AND MENTAL HEALTH-RELATED QOL IN CHRONIC CONSTIPATION Health-Re elated Qualit ty of Life 60 Chronic Constipation Matched Controls p<0.0001 p<0.0001 40 20 0 PCS MCS PCS= Physical Component Score MCS= Mental Component Score True False Sun et al, Dig Dis Sci 2011 56 2688-2695. www.seacourses.com 9
CHRONIC CONSTIPATION HAS SIGNIFICANT IMPACT ON THE QUALITY OF PATIENTS LIVES Andrews et al. Presented at DDW, May 19-23, 2012 www.seacourses.com 10
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, 2012 www.seacourses.com 11
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? www.seacourses.com 12
COMMON PATIENT DESCRIPTIONS OF CONSTIPATION 90 81 80 Physicians think: 72 < 3 BM per week 70 60 54 50 40 39 37 36 30 28 20 10 0 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 2001 96 3130-3137. www.seacourses.com 13
BRISTOL STOOL CHART Lewis SJ, Heaton KW. Scan J Gastroenterol 1997;32(9):920 924 www.seacourses.com 14
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 www.seacourses.com 15 15
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 2011 25(Suppl B) 11B-15B www.seacourses.com 16
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. 2011 Aug;23(8):697-710 1 www.seacourses.com 17
MYTH VS. FACTS In absence of alarm features what baseline labs or other tests should be done? www.seacourses.com 18
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 2013 144 218-238 Pare et al, Can J Gastroenterol 2007 21 (Suppl B) 3B-22B www.seacourses.com 19
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 2013 144 218-238 www.seacourses.com 20
Normal Transit Slow Transit Disordered Defecation True False www.seacourses.com 21
Normal Transit I go every day but the pieces are small and hard The MAJORITY of patients in primary care practice AGA, Gastroenterology 2013 144 218-238 Tack et al, Neurogastroenterology and Motility 2011 23 697-710 www.seacourses.com 22
Slow Transit I don t need to go for days at a time UNCOMMON in primary care practice ENS = enteric nervous system AGA, Gastroenterology 2013 144 218-238 Tack et al, Neurogastroenterology and Motility 2011 23 697-710 www.seacourses.com 23
Gastroenterology 2016;150:300 314 www.seacourses.com 24
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Disordered Defecation I push and strain and nothing comes out AGA, Gastroenterology 2013 144 218-238 www.seacourses.com 26
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TRUE OR FALSE? Drinking 6-10 glasses of water per day improves constipation? www.seacourses.com 28
Drinking 6-10 glasses of water per day improves constipation? True False AGA, Gastroenterology 2013 144 218-238 Ford et al, Alimentary Pharmacology & Therapeutics 2011 33(8) 895 Pare et al, Can J Gastroenterol 2007 21(Suppl B) 3B-22B Bove et al, World Journal of Gastroenterology 2012 18(36) 4994-5013 Muller-Lissner et al, Am J Gastroenterol 2005 100 232-242 www.seacourses.com 29
TRUE OR FALSE? Insoluble fibre helps constipation? www.seacourses.com 30
Insoluble fibre helps constipation? True False AGA, Gastroenterology 2013 144 218-238 Ford et al, Alimentary Pharmacology & Therapeutics 2011 33(8) 895 www.seacourses.com 31
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 http://www.dietitians.ca/nutrition-resources-a-z/factsheets/fibre/food-sources-of-fibre.aspx Ford et al, Alimentary Pharmacology & Therapeutics 2011 33(8) 895 www.seacourses.com 32
TRUE OR FALSE? Eating prunes improves constipation? http://www.dietitians.ca/nutrition-resources-a-z/factsheets/fibre/food-sources-of-fibre.aspx Ford et al, Alimentary Pharmacology & Therapeutics 2011 33(8) 895 www.seacourses.com 33
Eating prunes improves constipation? True False Attaluri et al, Aliment Pharmacol Ther 2011 33 822 www.seacourses.com 34
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 2013 144 218-238 Tack et al, Neurogastroenterology and Motility 2011 23 697-710 Pare et al, Can J Gastroenterol 2007 21(Suppl B) 3B-22B Ford et al, Alimentary Pharmacology & Therapeutics 2011 33(8) 895 www.seacourses.com 35
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 www.seacourses.com 36 ++ AGA, Gastroenterology 2013 144 218-238 Tack et al, Neurogastroenterology and Motility 2011 23 697-710 Pare et al, Can J Gastroenterol 2007 21(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. 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 www.seacourses.com 37
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 www.seacourses.com 38
PRUCALOPRIDE AND CHOLINERGICS: DIFFERENT MOA Prucalopride contracted relaxed Cholinergics www.seacourses.com 39 4
Linaclotide summary of mechanisms of action n=12 www.seacourses.com 40
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, http://www.practicalpainmanagement.com/opioid-induced-constipation-causes-treatments Thomas et al, J Palliative Med 2008 11(Suppl 1) S1-S19 www.seacourses.com 41
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. http://www.cwpcn.ca/uploads/relistor.1276171914.pdf; http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/relistor_hpc-cps-eng.php 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; http://www.purdue.ca/files/targin%20tablets%20pm%20en.pdf; http://www.purdue.ca/files/targin%20tablets%20pm%20fr.pd All marks above are the property of their respective owners www.seacourses.com 42
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 www.seacourses.com 43
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Questions www.seacourses.com 45