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1 อภ ชาต แสงจ นทร ภาคว ชาอาย รศาสตร คณะแพทย ศาสตร มหาว ทยาล ยขอนแก น

3 Functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits in the absence of detectable structural abnormalities

4 Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with two or more of the following: Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form of stool Criterion fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

5 Owyang C. Irritable bowel syndrome. Textbook of Gastroenterology 5 th edition 2009

6 IBS Subtype Talley NJ. Irritable bowel syndrome. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 9 th edition 2010

7 At primary care IBS is not the last resort diagnosis Consider a possible diagnosis of IBS in patients with main complaint of abdominal pain or discomfort Gwee K. J Gastroenterol Hepatol 2010

8 Gwee K. J Gastroenterol Hepatol 2010

9 Gwee K. J Gastroenterol Hepatol 2010

10 Gwee K. J Gastroenterol Hepatol 2010

11 Gwee K. J Gastroenterol Hepatol 2010

12 Gwee K. J Gastroenterol Hepatol 2010

Multifactorial disorder Genetic factors Aggregates within family, high concordance rate in monozygotic twin Motility disturbances Abnormal small bowel and colonic transit time Increase in colonic

13 Multifactorial disorder Genetic factors Aggregates within family, high concordance rate in monozygotic twin Motility disturbances Abnormal small bowel and colonic transit time Increase in colonic motility in response to meal Gut infections post-infectious IBS Higher prevalence of SIBO Brain-gut interactions Enhanced brain activations during gut stimulation Visceral hypersensitivity Gwee K. J Gastroenterol Hepatol 2010

14 ACG IBS Task Force. Am J Gastroenterol 2009

15 Treatment goal Symptom relief Improve QOL Chronic, relapsing course in nature Need effective Rx to reduce cost of investigation decrease suffering of the patients Good doctor-patient relationship Management should be individualized target all bothersome symptoms take into account of IBS subtypes, symptom severity

16 constant pain & psychological difficulties Intermittent symptom correlate with altered gut physiology Owyang C. Irritable bowel syndrome. Textbook of Gastroenterology 5 th edition 2009

17 Dietary history / food diary Dairy product Lactose and fructose-rich products Dietary fiber (form of bran or other cereals) Chili and curry Fiber Psyllium hydrophilic mucilloid (ispaghula husk) Fybrogel, Mucillin Improve global IBS symptom in IBS-C Bran (wheat or corn) or insoluble fiber Not effective

18 Antispasmodics Hyoscine, cimetropium, pinaverium and otilonium?mebeverine Provide short-term relief of abdominal pain/ discomfort? IBS-D Most of the trials predated classification IBS subgroups Adverse events Dry mouth, dizziness, blurred vision, urinary retention

19 Peppermint oil Colpermin Relax intestinal smooth muscle through antagonist effect on Ca channel Superior to placebo in reducing IBS symptoms pain reduction less abdominal distention Reduced stool frequency / pass less flatus 1-2 enteric coated capsule 3 times, 30 to 60 minutes before meals. Adverse events were very rare? Long term use Liu JH. J Gastroenterol 1997

20 Antidepressants Treatment of chronic pain Modulatory effects on pain perception Improve global IBS symptom Slow onset of action and substantial SE Try at least 4 weeks Need good compliance Patients preference are taken into account

21 Tricyclic antidepressant Amitriptyline, imipramine, trimipramine Prolong orocecal and whole gut transit time?ibs-d Prescription Daily dose at night time Starting at 10 mg mg.

22 Serotonin re-uptake inhibitors Fluoxetine, citalopram, paroxetine Promote general well-being, improvements in abdominal pain and bowel symptoms Effect is independent of improved depression Decrease orocecal and whole gut transit time?ibs-c

23 Loperamide Improve stool frequency and stool consistency Not effective than placebo for global IBS symptom and abdominal pain PEG laxative improve stool frequency but not abdominal pain in adolescents with IBS-C

24 Lubiprostone Prostaglandin E derivertive Poorly absorbed work topically in small bowel Selective C-2 chloride channel (ClC-2) activator promote chloride secretion into lumen stimulate colonic motility intraluminal volume or by unknown mechanisms Improve pain scores, stool consistency & straining compared to placebo in women with IBS-C

25 Lubiprostone Quality of life improvement in domains of health worry and body image FDA approve for women with IBS-C Adverse effects Nausea Diarrhea Headache

26 5-Hydroxytryptophan (5-HT) or Serotonin 95% of 5-HT is found in enterochromaffin cells throughout GI tract Acting through intrinsic and extrinsic afferent nervous system in GI tract Gut motility Visceral perception secretion

5-HT 4 receptor agonist Accelerate gastric emptying Improve gastric accommodation Accelerate small bowel / colonic transit Possibly decrease visceral sensation Tegaserod Effective in relieving global

27 5-HT 4 receptor agonist Accelerate gastric emptying Improve gastric accommodation Accelerate small bowel / colonic transit Possibly decrease visceral sensation Tegaserod Effective in relieving global IBS symptoms in female IBS-C and IBS-M Side effect diarrhea cardiovascular events withdrawn in 2007 MI, unstable angina, or stroke available through the FDA under an emergency investigational drug protocol

28 Antispasmodic & peppermint oil For diarrhea and abdominal pain 5-HT 3 receptor antagonist Delay GI transit Reduce colonic tone Blunt gastrocolic reflex Decrease visceral sensation Relieve abdominal pain, discomfort and urgency Alosetron & Ramosetron

29 Alosetron Superior to placebo and antispasmodic Relieve abdominal pain / discomfort / urgency Incidence of severe complication Ischemic colitis 1.1/1,000 patients-year Complicated constipation 0.66 / 1,000 patients-year Voluntarily withdrawn from market by drug company Re-release for use in female patients with severe IBS-D failed to respond to conventional therapy Starting at low dose 0.5 mg bid for 4 week then 1 mg. bid depend on clinical

30 Ramosetron New 5-HT 3 receptor antagonist Peripheral receptors No effect on CNS Improve global IBS symptom, abdominal pain / discomfort and bowel habit compare to placebo Ischemic colitis has not been reported with ramosetron

strains, and doses of probiotics used Single organism Bifidobacterium is effective in reducing IBS sysmptom Lactobacilli

31 Pathogenesis of IBS exposure to enteric pathogens, qualitative and quantitative changes in the enteric flora Probiotics Live microorganisms which when administered in adequate amounts confer a health benefit on the host Variety of species, strains, and doses of probiotics used Single organism Bifidobacterium is effective in reducing IBS sysmptom Lactobacilli is not effective Certain combinations of probiotics demonstrate some efficacy (Inforan : lactobacillus, bifidobacterium)

32 Rifaximin Nonabsorbable antibiotic Significantly improve IBS symptoms, bloating Most of the patients had IBS-D Neomycin Single small RCTs Improve global IBS symptoms Limitations Symptom relief last for weeks?risks related to long-term treatment of antibiotics

33 Combination Rx to target dominant symptom Diarrhea Loperamide Alosetron / Ramosetron Probiotics Constipation Fiber Osmotic / stimulant laxative Lubiprostone Abdominal pain / discomfort Antispasmodic Antidepressant Alosetron / Ramosetron Bloating Antibiotics Probiotics Tegaserod

34 ACG IBS Task Force. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol 2009; 104: S1-35 Ford AC. Irritable bowel syndrome. In McDonald JWD. Evidencebased gastroenterology & hepatology 3 rd edition 2010 Gwee KA, Bak YT, Ghoshal UC, et al. Asian consensus on irritable bowel syndrome. J Gastroenterol Hepatol 2010; 25: Saad RJ. Peripherally acting therapies for the treatment of irritable bowel syndrome. Gastroenterol Clin N Am 2011; 40: Spiller R, Aziz Q, Creed F, et al. Guideline on the irritable bowel syndrome: mechanisms and practical management. Gut 2007; 56:

36 George F. Gastroenterology 2006

37 Primary Constipation Normal transit constipation Stool traverses at a normal rate & the frequency is normal Patients believe that they are constipated due to a perceived difficulty with evacuation the presence of hard stool. Slow transit constipation (Colonic inertia) Prolonged stool transit through colon & reduce rectal sensation Defecation disorders (Pelvic floor dysynergia, anismus) Difficult or unsatisfactory expulsion of stool from rectum Dyssynergic defecation, impaired perineal descent?constipation-predominant IBS Lembo A et al. NEJM 2003 Gallegos-Grozco JF. Am J Gastroenterol 2011

40 Secondary Constipation Drug Anticholinergic TCA, neuroleptic agent, antiparkinsonian drugs Antihypertensives Ca channel blockers, clonidine Cation-containing agents Iron, Ca, aluminium-containing antacid, sucralfate Opiates Morphine, codeine Gallegos-Grozco JF. Am J Gastroenterol 2011

41 Secondary Constipation Structural abnormalities Perianal disease : Fissure Colonic stricture : Carcinoma, IBD, diverticulitis, radiation, ischemia Systemic disease Metabolic and endocrine : DM, hypothyroidism, hypercalcemia, hypokalemia Neurologic disorder : Parkinson s disease, spinal cord lesion, multiple sclerosis Others : Dermatomyositis, scleroderma Gallegos-Grozco JF. Am J Gastroenterol 2011

42 Tack J. Neurogastroenterol Motil 2011

43 Tack J. Neurogastroenterol Motil 2011

44 CBC Blood sugar, electrolyte, calcium Thyroid function test Stool occult blood BE/ colonoscopy

45 Specific treatment Treat underlying disease Symptomatic treatment Non-pharmacologic management Provide education to improve toileting Gastrocolic reflex Give priority to bowel movlement Review of medicine Adequate fiber intake(30 g/day) Regular physical activity

46 Fiber / Bulking agents Source Natural: bran, psyllium Synthetic: methylcellulose, calcium polycarbophil Improve stool weight and consistency Side effects flatulence, bloating Stool softeners Act as detergents between water and solid stool Docusate sodium/calcium

47 Stimulant laxatives Mechanism Stimulatory effects of myenteric plexus Inhibiting water absorption Senna, cascara, bisacodyl Side effects Abdominal cramping Electrolyte disturbance

48 Poorly absorbed ions or molecules Increase stool water content softer, ease of propulsion MOM, Lactulose, PEG Lactulose VS. PEG* PEG is better than lactulose in terms of higher stool frequency per week higher Bristol Stool Score require less use of additional products improve abdominal pain *Lee-Robichaud H. Cochrane Review2011

Lubiprostone Prostaglandin E derivertive Chloride channel activator Poorly absorbed work topically in small bowel Selectively activate type 2 Cl channel at apical

49 Lubiprostone Prostaglandin E derivertive Chloride channel activator Poorly absorbed work topically in small bowel Selectively activate type 2 Cl channel at apical membrane of enterocyte promote chloride secretion into the intestine Increase stool water content stimulate colonic motility by increasing intraluminal volume /?mechanism

50 Lubiprostone Significantly increase bowel movement frequency and relieve other constipation-related symptom compare to placebo No sig. electrolyte changes with prolonged use of lubiprostone. Adverse effects Nausea Headache

51 Highly selective 5-HT 4 receptor agonist No metabolism through CYP3A4 less drug-drug interaction than other drugs in this class Transit studies Improve gastric emptying, small bowel transit, overall colonic transit Phase III trials Improve bowel movements, constipation-related symtoms and QoL Effective in elderly and patients with opioidinduced constipation

52 Transient common adverse reactions Headache Nausea Abdominal pain No effect on QT interval

meta-analysis. Gut 2011;60:209-218 Gallegos-Orozco JF, Foxx-Orenstein AE,Sterler SM, et al.

53 Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut 2011;60: Gallegos-Orozco JF, Foxx-Orenstein AE,Sterler SM, et al. Chronic constipation in elderly. Am J Gastoenterol 2011; doi: /ajg Tack J, Muller-Lissner S, Stanghellini V, et al. Diagnosis and treatment of chronic constipation-a European perspective. Neurogastroenterol Motil 2011; 23:

Advancing gastroenterology, improving patient care

American College of Gastroenterology Advancing gastroenterology, improving patient care Note to Visitors: A fully updated ACG Systematic Review on the Management of Chronic Idiopathic Constipation and