FUNCTIONAL BOWEL DISORDERS

1. FUNCTIONAL BOWEL DISORDERS CURRENT APPROACH TO IRRITABLE BOWEL SYNDROME

2. INTRODUCTION: Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain associated with altered bowel habits in the absence of any organic cause.

3. IBS • Prevalence is 10-15% in the USA • Second leading cause of work absenteeism in the USA • 2:1 Female to Male predominance in the USA • Equally prevalent in India however.

4. CLINICAL FEATURES OF IBS Abdominal pain is quite variable: Location Intensity Duration

5. Characteristic Features of IBS Abdominal Pain: • Pain that is improved when recumbent • Pain that typically does not awaken the patient from sleep • Pain that changes location • Pain that is improved or worsened by passage of stool or gas

6. ALTERED BOWEL HABITS • Variable stools—pellet like, ribbon like, malodorous • Urgency, straining at defecation, difficulty with stool expulsion • Sensation of incomplete evacuation, mucus • Chronic diarrhea, chronic constipation, diarrhea alternating with constipation

7. Other complaints associated with IBS: • GE Reflux • Early Satiety, dyspepsia, nausea • Abdominal Distention, flatulence, belching • Non-cardiac chest pain

8. Other complaints associated with IBS (continued) • Sexual dysfunction, dysmenorrheal, dyspareunia • Urinary frequency • Hypertension, asthma, and fibromyalgia

9. MANNING CRITERIA FOR IBS • Pain relieved with defecation • More frequent stools at onset of pain • Looser stools at onset of pain • Visible abdominal distention • Passage of mucus • Sensation of incomplete evacuation The likelihood of IBS is proportional to the number of Manning’s criteria that are present

10. ROME CRITERIA FOR IBS In the absence of structural or metabolic abnormalities, with at least 12 weeks or more—which need not be consecutive, in the preceeding 12 months—of abdominal pain with two of three following features: • Pain relieved with defecation, and/or • Pain onset associated with change in stool pattern, and/or • Pain onset associated with change in stool form or appearance

11. Rome criteria, symptoms that cumulatively support diagnosis of IBS • Abnormal stool frequency • Abnormal stool form • Straining, urgency or sense of incomplete evacuation • Passage of mucus • Abdominal distention

12. Etiology of IBS: • ?Motility Disorder • ?Post Infectious Immune Reaction • ?Anxiety Disorder • ?Visceral Hyperalgia • ?Dietary Fiber Deficiency

13. General Principles of Management of IBS IBS is considered a chronic condition with no known cure. The focus of treatment should be on symptom relief and in addressing the patient's concerns. Exacerbating factors (such as medications and diet), stress, or psychiatric disorders should be identified if possible.

14. General Principles in Management of IBS(continued) • Therapeutic physician-patient relationship • Dietary Modification • Antispasmotics • Benzodiazepines — Anxiolytic agents • Low dose Anti-Depressants

15. 5-hydroxytryptamine (serotonin) 3 receptor antagonistsAlosetron (Lotronex) • Somewhat beneficial in diarrhea predominant IBS, but women only • Two studies demonstrated significant benefit—pain reduction of 41% versus 28% in comparison to placebo. Response typically occurred first 4 weeks of therapy and was sustained. • Dose is 2 mg po BID

16. Alosetron (Lotronex)(continued) • Caution: Severe ischemic colitis was reported in 84 patients to FDA within first year of release, with 54 requiring hospital admission, 11 required surgery and there were two deaths. • An additional 83 patients required hospitalization for severe constipation, 34 of whom required surgery, and there were also two deaths.

17. 5-hydroxytryptamine (serotonin) 4 receptor agonistsTegaserod (Zelnorm/Zelmac) • Beneficial in constipation predominant IBS • Dose is 6 mg po BID • Three clinical trials in almost 2,500 patients with IBS reported control of pain, distention, and constipation. However, margin of benefit was low—just 5-10% symptom response over placebo. Maximum benefit was noted early phase of study suggesting possible tachyphylaxis.

18. Adverse Effects of Tegaserod • Generally well tolerated—higher incidence of diarrhea (9% vs. 4% for placebo) • Reports of small increased incidence of cholecystectomy of uncertain significance. • Not carcinogenic, teratogenic, or toxic to the fetus in animal studies • No significant drug interactions observed

19. Contraindications to Tegaserod • Severe renal impairment • Moderate or severe hepatic impairment • History of bowel obstruction • Symptomatic gallbladder disease/or suspected sphincter of Oddi dysfunction • ?Abdominal adhesions • Known allergy to the drug or any of its excipients

20. Summary of Evaluation and Management of IBS • IBS is defined by chronic abdominal pain and an alteration in bowel habits • Numerous other complaints are associated with IBS • Stress and Anxiety may be provocative factors, but not thought etiologic • Alosteron should be used with caution in IBS due to catastrophic side effects • Tegaserod appears safe, but only marginally effective, will not be a panacea • No currently available and reliable treatment for Intestinal Gas complaints

21. HORSE SENSE Physicians can be classified as: • “LUMPERS” or • “SPLITTERS”

22. VARIABILITY IN PRESENTATION OF ACUTE MYOCARDIAL INFARCTION • Stroke • Pulmonary Edema • Syncope • Sudden Death • Severe Heartburn • Jaw, Neck Pain or Arm Pain • Tachycardia • Etc.

23. Variability in the Clinical Features of Functional Bowel Disorders: • Functional Abdominal Pain • Alteration in Bowel Habits/Urgency • Abdominal Distention • Flatulence/Borborygmi • Aerophagia • Upright Refluxers (Regurgitation) • Proctalgia Fugax • Sensation of Incomplete evacuation of stools

24. Normal Bowel Habits (Current Dogma) In a study of two population samples, AM Connell found that 99% of the population passed between three stools weekly to three stools daily. This finding has impacted GI research for decades. AM Connell, BMJ 1965, 2:1095

25. Expanded Criteria for Constipation At least 12 weeks which need not be consecutive in the preceeding 12 months of 2 or more: • Straining in > ¼ defecations • Lumpy or hard stools > ¼ of defecations • Sensation of incomplete evacuation in > ¼ of stools • Sensation of anorectal obstruction in > ¼ of stools • Manual manuevers to facilitate > ¼ defecations • < 3 defecations per week • Loose stools are not present and insufficient criteria for diagnosis of IBS • (see Locke et al)

26. Basic Concepts in Managing Functional Bowel Disorders: • The goal is to achieve 1-4 large soft stools daily with minimal odor • Begin with small amount of soluble fiber, preferably Methylcellulose BID (e.g. ½ TBSP) • Consider beginning with an osmotic laxative daily, adjust dose to achieve stated above stated goal

27. Basic Concepts in Management (continued) • Gradually increase the soluble fiber dose—BID or TID preferable • Once excellent stools, continue the osmotic laxative daily, but gradually reduce the dose • If much distention, reduce the fiber dose, and/or increase the osmotic laxative • For difficult patients, consider glycerine suppositories and/or tap water enemas as often as daily if needed for symptom control

28. Case # 1 • RJ--12 yo straight A student presented with severe, recurrent abdominal pain (RAPS) and alternating diarrhea and constipation. Also complained of incomplete stool evacuation. • Initially patient required fleets enema for partial symptom relief. • Asymptomatic on 4 gm psyllium once daily • Symptom relapse frequently occurs within 1-2 days if non-compliant with psyllium • 6 year followup

29. Case # 2 • TC—38 yo man with 15 year history of severe IBS, manifest by attacks of severe lower abd. pain, diarrhea, distention, N/V requiring frequent admissions, 3-4 in past one year. Symptoms especially provoked by travel. • Constipated when not having attacks • Work up included multiple EGD’s, colonoscopies, CT scans, SBFT study, small bowel biopsy, EEG, gastric emptying study

30. CASE # 2 (continued) • Prior appendectomy and cholecystectomy without benefit • Tried numerous medications, including anti-spasmotics, metoclopramide, omeprazole, SSRI’s, tranquilizers, Citrucel and used prn miralax (PEG) • Followed at local university medical center by a world reknown IBS specialist

31. CASE # 2 (continued) • Patient started on regimen of Citrucel (methyl cellulose) BID, which was increased as tolerated • He was instructed to take Miralax daily and to adjust the dose to achieve excellent stools daily • 2 admissions first 3 months after evaluation with severe attack • No further episodic attacks of pain or N/V— subsequent 12 months symptom free • Now on fiber cereals and Benefiber (guar gum), and off Citrucel and Miralax

32. CASE # 3 • DG—49 yo woman presented in 1996 with 1 year h/o intractable GE Reflux/heartburn • EGD was normal. Esophageal manometry was c/w GE reflux. No 24 hr. pH study • Stools were 3/week. No distention. Psyllium worsened her complaints • No response to PPI’s BID and cisapride

33. CASE # 3 (continued) • A partial fundoplication (Toupee) did not control her GE Reflux symptoms. • Six months later, an open Nissen fundoplication again, no symptom response • In 1998, Citrucel BID plus milk of magnesia PRN was initiated. • Once excellent bowel habits achieved, all PPI’s were stopped. Now uses ranitidine PRN only.

34. GOAL OF THERAPY FOR FIBER SUPPLENTATION: • Based upon 20 years of experience as a gastroenterologist, the goal of my patients is to achieve 2-4 large soft stools daily with minimal odor. • Stool volume should be 600 to 1,000 cc daily of soft stools with minimal odor. Note: patients < age 40 may find that 1-3 large soft stools may be satisfactory

35. Constipation and “not know it!” Just as a patient can have a heart attack without chest pain, or any other symptoms for that matter, one be constipated and “not know it.” That is, one can have regular stools daily and “still be constipated.” Foul smelling stools are as indicative of constipation as hard stools, or infrequent stools.

36. The Paradox Fiber and Increased Abdominal Pain and Gas: Once fiber is introduced, due to fact it is not digested and thus can be fermented in the large bowel, one should initially expect some increase in functional abdominal symptoms, until excellent bowel habits are achieved—which explains the paradox of why dietary fiber may initially exacerbate functional bowel disorders.

37. Citrucel (methylcellulose) Causes Less Gas Initially Plastic is made from oil, and then basically ground up to make Citrucel/Methyl-cellulose. Since people do not regularly ingest oil or plastic for that matter, the bacteria that colonize the colon cannot ferment it very efficiently. However, after a number of months, they begin to recognize methylcellulose and can ferment it.

38. A Spastic Colon is like a Railroad Car 20 or 30 men can get a railroad car rolling on level tracks by using ropes and pulleys. However, once the inertia of that heavy railroad car is overcome, just 2 or 3 men can keep it rolling down the tracks. The colon is much like a heavy railroad car that sits on the railroad track. Osmotic laxatives or infrequently tap water enemas may be required to overcome this inertia.

39. SUMMARY In Summary, functional bowel disorders include a large variety of unexplained abdominal complaints. Dietary intervention is successful in controlling even the most difficult patients with IBS. I usually begin with 0.5 gm of Citrucel BID and increased as tolerated to 4 gm. BID. Frequently patients require an osmotic laxative, which should be taken initially on a daily basis.

40. SUMMARY (continued) • Once excellent bowel habits are achieved, other forms of soluble dietary fiber is encouraged. Due to the many years of a low fiber diet and small volume stools, significant resistance may be encountered when fiber is first introduced. For this reason, IBS symptoms may initially flare as patients adapt to the dietary change.