Irritable Bowel Syndrome

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1 Irritable Bowel Syndrome

2 Functional gastrointestinal disorders Definition A variable combination of chronic or recurrent gastrointestinal symptoms (attributed to the pharynx, esophagus, stomach, biliary tree, small or large intestine, or anorectum) not explained by structural or biochemical abnormalities. Rome criteria, 1990

3 FGIDs including

4 The Rome III criteria divided Functional Gastrointestinal Disorders (FGIDs) into 8 dignostic classification adult (6 classification) children and adolescents(2 classification)

5 Rome III Functional Gastrointestinal Disorders (adult ) A. Functional esophageal disorders A1. Functional heartburn A2. Functional chest pain of presumed esophageal origin A3. Functional dysphagia A4. Globus B. Functional gastroduodenal disorders B1. Functional dyspepsia B1a. Postprandial distress syndrome B1b. Epigastric pain syndrome B2. Belching disorders B2a. Aerophagia B2b. Unspecified excessive belching B3. Nausea and vomiting disorders B3a. Chronic idiopathic nausea B3b. Functional vomiting B3c. Cyclic vomiting syndrome B4. Rumination syndrome in adults C. Functional bowel disorders C1. Irritable bowel syndrome C2. Functional bloating C3. Functional constipation C4. Functional diarrhea C5. Unspecified functional bowel disorder D. Functional abdominal pain syndrome E. Functional gallbladder and Sphincter of Oddi (SO) disorders E1. Functional gallbladder disorder E2. Functional biliary SO disorder E3. Functional pancreatic SO disorder F. Functional anorectal disorders F1. Functional fecal incontinence F2. Functional anorectal pain F3. Functional defecation disorders

Rome III Functional Gastrointestinal Disorders (children and adolescents) G. Functional disorders: neonates and toddlers G1. Infant regurgitation G2. Infant rumination syndrome G3.

6 Rome III Functional Gastrointestinal Disorders (children and adolescents) G. Functional disorders: neonates and toddlers G1. Infant regurgitation G2. Infant rumination syndrome G3. Cyclic vomiting syndrome G4. Infant colic G5. Functional diarrhea G6. Infant dyschezia G7. Functional constipation H. Functional disorders: children and adolescents H1. Vomiting and aerophagia H1a. Adolescent rumination syndrome H1b. Cyclic vomiting syndrome H1c. Aerophagia H2. Abdominal pain-related functional gastrointestinal disorders H2a. Functional dyspepsia H2b. Irritable bowel syndrome H2c. Abdominal migraine( 偏头痛 ) H2d. Childhood functional abdominal pain H2d1. Childhood functional abdominal pain syndrome H3. Constipation and incontinence

with altered bowel habits or disturbed defecation - relieve after

7 Definition Irritable Bowel Syndrome A functional GI disorder characterized - abdominal pain and/or discomfort - associated with altered bowel habits or disturbed defecation - relieve after defecation Not explained by structural or known biochemical abnormalities

8 IBS - Epidemiology 12-22% 15% 19% 14% 8-12% 9% 16% Drossman. DPS 1993;Sandler. GE 1984;Jones. MJ 1992;Thompson. DDS 2002

9 IBS - Epidemiology U.S. Prevalence % >60 age in years male female

10 IBS - Epidemiology Doctor Visits by Gender

11 IBS - Epidemiology Prevalence of Diagnosis Primary Care Practice Gastroenterology Practice

12 IBS - Epidemiology Work or School Absences Days per Year IBS Normal

13 IBS - Epidemiology Among the common diseases impact work because of sickness IBS is just in second only after Upper respiratory tract infection SECOND

14 IBS - Epidemiology Up to 10-20% of population Females > males Younger > older 2/3 do not seek health care 12% primary care practice, 28% GI practice >3x work loss, M.D. visits

15 Pathophysiological mechanisms Abnormal motility Visceral hypersensitivity Brain-gut interactions dysfuction Gut inflammation Psychosocial Factors

16 Pathophysiological mechanisms 1. Altered gut reactivity (motility, secretion) in response to luminal (e.g., meals, gut distention, inflammation, bacterial factors) provocative environmental stimuli, (e.g., psychosocial stress) resulting in symptoms of diarrhea and/or constipation 16

17 IBS - Abnormal motility Sigmoid Motility Index Minutes

IBS - Abnormal motility Normal Migrating Motor Complex (MMC) Phase I 15-30 minutes Quiescence Phase II 60

18 IBS - Abnormal motility Normal Migrating Motor Complex (MMC) Phase I minutes Quiescence Phase II 60 minutes Irregular contractions Phase III 4-7 minutes Propagated contractions Interdigestive 90 minute cycle

19 IBS - Abnormal motility Prolonged Propagated Contractions (PPCs) More common in IBS Occur in ileum Peristaltic Correlate strongly with pain (IBS patients)

20 IBS - Abnormal motility Discrete Clustered Contractions (DCCs) Phase II of MMC More common in IBS Nonspecific - Obstruction - Pseudo-obstruction Correlates weakly with pain

21 Pathophysiological mechanisms 2. A hypersensitive gut with enhanced visceral perception and pain 21

22 IBS - Visceral hypersensitivity % Reporting Pain Rectosigmoid balloon inflation volume (ml)

23 Pathophysiological mechanisms 3. Dysregulation of the brain-gut axis possibly associated with greater stress-reactivity and altered perception and/or modulation of visceral afferent signals 23

24 IBS brain-gut interaction Brain-Gut Axis Afferent / efferent impulse

25 IBS - brain-gut interaction Enteric Nervous System Independently controls gut function Exhibits simple programmed functions (e.g., MMC, peristalsis) Intrinsic pacemaker controls rhythm Contains multiple neurotransmitters Actions modified by vagal and sympathetic extrinsic nerves

26 IBS - brain-gut interaction Sensitization of visceral afferent fibres Altered spinal modulation Abnormal sensory perception Central Processing Dysregulation of the brain-gut axis Spasm of GI smooth muscle abdominal pain 26

27 Pathophysiological mechanisms 4 Inflammation: gut inflammatory and immune factors persisting following infection or inflammation of the bowel 27

28 Role of psychosocial factors 1) Psychological stress exacerbates GI symptoms. 2) Psychological disturbances modify the experience of illness and illness behaviors such as health care seeking. 3) Psychosocial factors affect health status and clinical outcome. 28

29 Increased motor reactivity Altered visceral sensation CNS - ENS dysregulation inflammation Involves small and large intestine

Clinical manifestation Symptoms of Irritable Bowel Syndrome can include: abdominal pain/discomfort (often relieved by passing a bowel motion)(essential) Altered defecation (frequency features)

30 Clinical manifestation Symptoms of Irritable Bowel Syndrome can include: abdominal pain/discomfort (often relieved by passing a bowel motion)(essential) Altered defecation (frequency features) Constipation diarrhea (sometimes one alternating with the other) abdominal bloating Headaches/backache Poor appetite/weight loss Fatigue and Sleeplessness Anxiety or Depression These symptoms can occur in any combination or individually

31 Diagnosis approach

32 Diagnosis Diagnostic Criteria* for Irritable Bowel Syndrome (The Rome III) Recurrent abdominal pain or discomfort** at least 3 days per month in the last 3 Months associated with 2 or more of the following: 1. Improvement with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form (appearance) of stool *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. **

33 IBS - Diagnosis Rome Criteria Symptoms >3 months Abdominal pain/discomfort - Relieved with defecation and/or - With change in stool frequency and/or - With change in stool consistency Two or more at least 1/4 of the time - in stool frequency - in form - Difficult passage - Mucous - Bloating

34 Bristol Stool Form Scale 1-7

35 IBS subtyping The Rome II Irritable bowel syndrome (IBS) diarrhea-predominant pattern constipation-predominant pattern diarrhea- constipation alterative pattern The Rome III Irritable bowel syndrome (IBS) IBS with constipation (IBS-C) IBS with diarrhea (IBS-D ) Mixed IBS (IBS-M) Unsubtyped IBS

36 IBS-Subtypes (Rome III Criteria) (IBS- Constipation) (IBS-Diarrhea) (IBS-Mixed) (IBS-Unsubtyped) unsubtyped Hard and lumpy stools 25%,and watery and loose stools<25% Watery and loose stools 25%,and hard and lumpy stools<25% Hard and lumpy stools 25%,also watery and loose stools 25% Hard and lumpy :Bristol 1~2;watery and loose: Bristol 6~7

37 Two-dimensional display of the 4 possible IBS subtypes according to bowel form at a particular in time (George F. Longstreth et al. Functional Bowel Disorders. Gastroenterology 2006;130: )

38 IBS-C 19%-44% IBS-D 15%-36% IBS-C IBS-D IBS-A/M IBS-A/M 19%-49% 75% patients alternated subtypes Simren et al, Scand J Gastroenterol 2001; 36:545 Tillisch et al, Am J Gastroenterol 2005; 100:896Mearin et al, Eur J Gastroenterol Heoatol 2003; 15:165 Drossman et al, Gastroenterology 2005; 128:580

39 IBS - Diagnosis Additional Specialized Studies Constipation Diarrhea Pain / Bloating Colonic transit Anal manometry and balloon expulsion Rectal sensation and emptying Defecography Stool osmolarity and electrolytes Laxative screen Small bowel / colonic transit Rectal sensation 75 SeHCAT test / Cholestyraminetrial Smal bowel series Antidepressanttrial CHO-H 2 breath test Small bowel manometry

40 IBS - Diagnosis Dietary Factors Lactose Caffeine Alcohol Fat Gas-producing foods Malabsorption Post-gastrectomy Intestinal Pancreatic Infection Giardia lamblia Bacterial Ameba Differential Diagnosis Miscellaneous Endometriosis Endocrine tumors (Carcinoid, VIP, etc.) AIDS Inflammatory Bowel Ulcerative colitis CD Microscopic colitis Mast-cell disease Pschychologic Anxiety/panic Depression Somatization

41 IBS - Diagnosis Historical Weight loss Onset in older patients Nocturnal awakening Family Hx CA / IBD Physical Abnormal exam Fever Positive occult stool Initial Labs Hgb WBC ESR Abnormal chemistry

42 Treatmemt 1.General treatment approach 2. Pharmacological therapies 3.Psychological therapies

43 General treatment approach 1. Establish therapeutic relationship 2. Education and reassurance 3. Dietary and lifestyle modifications

44 IBS general Treatment Approach Physician-Patient Relationship Reassure the patient that they are not unusual Identify why the patient is currently presenting Obtain a history of referral experiences Examine patient fears or agendas Ascertain patient expectations of physician Determine patient willingness to aid in treatment Uncover the symptom most impacting quality of life and the specific treatment designed to improve management of that symptom

45 IBS general Treatment Approach Education and reassurance Education about healthy life style behaviors, Patients should have regular, unhurried meals reassurance that the symptoms are not due to a life-threatening disease

46 IBS general Treatment Approach Dietary Modifications Eliminate offending items - Lactose - Sorbitol gum - Caffeine - Large meals - Fatty foods - Food sensitivity - Alcohol - Gas producing foods Increase fiber (consipation)

47 Pharmacological therapies drug therapy for IBS can be considered in two categories: 1. End organ treatment aimed at relieving abdominal pain (antispasmodic drugs) or disturbed bowel habit (antidiarrhoeal and bulking agents). 2. Central treatment (antidepressants) targeted at patients with associated affective disorder.

antagonists Trimebutine Antidepressants (low dose initially)

48 IBS pharmaceutical Treatment Pharmaceutical Agents Pain Diarrhea Constipation Antispasmodics Anticholinergics selective Ca++ antagonists Trimebutine Antidepressants (low dose initially) Loperamide Diphenoxylate Cholestyramine Fiber Osmotic laxatives Cisapride Misoprostil PEG solution

49 Antispasmodics Pharmacological therapies Anticholingergic drugs may provide temporary relief for symptoms such as painful cramps related to intestinal spasm Selective Ca++ antagonists (Pinaverium Bromide, Otilonium Bromide ) Smooth muscle relaxant papaverine peripherally acting opiate-based agonist (Trimebutine)

50 Antidiarrheal Pharmacological therapies Peripherally acting opiate-based agents Loperamide 2-4mg erery 4-6hours up to maximum of 12g/d, Diphenoxylate Cholestyramine bile acid binder

51 Pharmacological therapies Anti-constiption High fiber diets and bulking agents Water-holding action of fibers contribute to increase stool bulk, speed up colonic transit. improve in constipation. psyllium produced greater improvement in stool pattern and abdominal pain than bran, it tends to produce less bloating and distention Osmotic laxatives(e.g. lactulose)

52 Pharmacological therapies Serotonin Receptor Agonist and Antagonists Serotonin 3 receptor agonist for IBS-D alosetron reduces perception of painful visceral stimulation in IBS, also induce rectal relaxation, increases rectal compliance, and delay colonic transit, especially efficacious in women Serotonin 4 receptor antagonist for IBS-C Misoprostil Cisapride Tegaserod exhibit prokinetic activity by stimulating peristalsis, acceleate intestinal and ascending colonic transit in IBS-C

53 Psychological therapies Cognitive-behavioral treatment Antidepressants are recommended for moderate to severe symptoms - tricyclic antidepressant in IBS-D -selective serotonin reuptake inhibitor(ssri)- IBS-C Psychological treatments are initiated when symptoms are severe enough to impair health-related quality of life. -standard psychotherapy -hypnotherapy

54 Irritable bowel syndrome Definition:abdominal pain or discomfort and altered bowel habits without demonstrable organic disease. Pathophysiological mechanisms Clinical Features: 1. Diarrhea-predominant; 2. Constipation-predominant; 3. Mixed Diagnosis: Rome III Criteria Treatment: 1.General treatment approach; 2. Pharmacological therapies 3.Psychological therapies

55 IBS 诊治流程

CHAPTER 11 Functional Gastrointestinal Disorders (FGID) Mr. Ashok Kumar Dept of Pharmacy Practice SRM College of Pharmacy SRM University

CHAPTER 11 Functional Gastrointestinal Disorders (FGID) Mr. Ashok Kumar Dept of Pharmacy Practice SRM College of Pharmacy SRM University 1 Definition of FGID Chronic and recurrent symptoms of the gastrointestinal