4) Irritable Bowel Syndrome - Dr. Shaikhani. Epidemiology. Pathophysiology. Burden. Diagnosis

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1 4) Irritable Bowel Syndrome - Dr. Shaikhani Epidemiology A common disorder, with a 7% prevalence. Women are 1.5 times more likely to be affected than men, most commonly between ages years. Onset after the age of 50 years is uncommon. Pathophysiology Not well understood, may vary depending on the subtype & include: o Abnormal GIT motility o Visceral afferent hypersensitivity o Autonomic innervation abnormalities. o Altered mucosal immune system activation may occur, particularly in patients with diarrhea who develop symptoms after an acute gastroenteritis (postinfectious IBS). o Depression, anxiety, a H/O sexual abuse, phobias, somatization are commonly associated, but not psychosocial factors. o Health-related quality of life (HRQOL) scores are lower in IBS than in unaffected persons, but? Cause or effect. o IBS patients who seek evaluation& treatment are more likely to have comorbid psychiatric illness& psychological stress is likely to exacerbate symptoms. Burden IBS is costly, with direct & indirect (including decreased work productivity) costs estimated at $20 billion, with IBS patients consuming > 50% more in health care resources than matched controls. Increased health care utilization in IBS patients is directly related to somatization levels. Diagnosis Based solely on clinical grounds. As no biochemical, radiographic, endoscopic or histologic marker exists, the diagnosis depends on Rome criteria. Now depends on Rome 3, but only Rome I criteria have been evaluated for accuracy, with a sensitivity of 71% & specificity of 85%. The ACG task force on IBS has recommended a simpler definition: Abd pain associated with altered bowel habits (change in stool form or frequency) over a period of at least 3 months. Rome 3 o Recurrent abd pain or discomfort (abn sensation not described as pain) at least 3 days a month in past 3 months (with onset > 6 months prior) associated with two or more of the following: o Improvement with defecation o Onset associated with change in frequency of stool o Onset associated with change in form (appearance) of stool o Absence of alarm indicators that suggest other diseases: o Age >50 years o Male o Short history of symptoms o Documented weight loss o Nocturnal symptoms o Family history of colon cancer o Rectal bleeding o Recent antibiotic use 1 P a g e

2 Bowel habit subtype classification IBS with constipation (IBS-C) o Hard or lumpy stools 25% of bowel movements o Loose (mushy) or watery stools <25% of bowel movements IBS with diarrhea (IBS-D) o Loose (mushy) or watery stools 25% of bowel movements o Hard or lumpy stools <25% of bowel movements Mixed IBS (IBS-M) o Hard or lumpy stools 25% of bowel movements o Loose (mushy) or watery stools 25% of bowel movements Unsubtyped IBS o Insufficient abnormality of stool consistency to meet criteria for IBS-C, D, or M Supportive symptoms may include: o Abnormal stool frequency (>3/d, <3ds/week) o Abnormal stool form (lumpy/hard or loose/watery) o Straining or urgency or a sensation of incomplete evacuation, mucus o Bloating. Meeting the diagnostic Rome criteria for IBS & the absence of alarm symptoms& signs regarded as reassuring that the patient does not have organic disease such as IBD, CRC or celiac disease. Recent review of the literature has suggested that nocturnal symptoms as well as rectal bleeding in particular are not helpful in separating IBS from patients with organic disease. While other alarm criteria such as anemia& weight loss lack sensitivity for the diagnosis of organic disease, they are specific. Affected patients may describe non GIT somatic symptoms such as headache, urinary symptoms, backache, and fatigue. Differential diagnosis of IBS symptoms Infection Parasitic HIV and associated infections Viral gastroenteritis Amoebic infections Giardiasis Food and diet Lactose intolerance Fructose intolerance Fatty foods Alcohol Caffeine Food allergy Artificial sweeteners Other functional GI disorders Functional abdominal pain Functional dyspepsia Functional diarrhea/constipation IBD or other organic GI disorders Crohn's disease Ulcerative colitis Microscopic/collagenous colitis Celica disease Ischemic colitis Bowel obstruction Pancreatic insufficiency Bile acid related disorders Postgastrectomy disorders Gynecologic conditions Endometriosis Dysmenorrhea Ovarian cancer Neurologic conditions Spinal cord pathology Multiple sclerosis Parkinson's disease Endocrine or metabolic disorders Thyroid disorder Diabetes mellitus Pancreatice endocrine tumors Hypercalcemia Acute intermittent porphyria Psychiatric disorders Panic disorder Somatization Anxiety disorder GI symptoms related to medications Antibiotics Chemotherapy agents Opiates Antidepressants NSAIDs PPIs Antihypertensive agents (e.g. Ca + - channel blockers) 2 P a g e

Evaluation Patients with potential IBS should not undergo a potentially expensive or harmful evaluation that may undermine their confidence in the diagnosis& in the physician.

3 Evaluation Patients with potential IBS should not undergo a potentially expensive or harmful evaluation that may undermine their confidence in the diagnosis& in the physician. Anemia is an alarm sign; a complete blood count should be performed after the onset of symptoms. Patients with IBS with diarrhea & mixed IBS should have serologic tests for celiac disease, which occurs more commonly in patients with these IBS subtypes than in the general population. A possible link between IBS& small intestine bacterial overgrowth, but ACG not recommend routine testing. Testing for lactose intolerance, more common among IBS, should be conducted only if this diagnosis is unclear on clinical grounds. Colonoscopy is indicated only if patients are > 50 years. In any patient with alarm features, further evaluation is mandated& should be tailored to symptoms; i.e patients with constipation need imaging to rule out a mechanical obstruction. In patients with IBS with diarrhea who undergo colonoscopy, biopsies of the colon should be done to evaluate for microscopic colitis, particularly if there is suggestion of a secretory diarrhea. ACG IBS Task Force recommendations for diagnostic testing Diagnostic test Recommendations Routine blood tests (complete blood Should only be performed if alarm symptoms are present count, chemistries, thyroid function, stool ova/parasites) Celiac disease serology Recommended in IBS-M and IBS-D Abdominal radiological imaging Should only be performed if alarm symptoms are present Colonoscopy Recommended if alarm symptoms/signs are present to rule out organic disease Recommended in patients aged 50 years for routine screening Not recommended if no alarm symptoms in patients aged <50 years with typical IBS symptoms Colonic biopsies are recommended if performing a colonoscopy in IBS-D to rule out microscopic colitis Breath testing to rule out lactose Only recommended if clinical suspicion is high and exclusion diet has failed intolerance Breath testing for SIBO Not routinely recommended due to insufficient data Treatment Depends on a patients predominant symptoms. Although patients often link diet to symptoms, no clear data support elimination diets or food allergy testing, but if individual patients identify clear food triggers, these can be eliminated or reduced. 3 P a g e

4 Treatment for CP-IBS Bulking agents, especially fiber in the form of psyllium hydrophilic mucilloid (ispaghula husk) & calcium polycarbophil, may improve global IBS symptoms but can be associated with bloating & flatulence. Laxatives appear to be effective in chronic constipation; although laxatives appear to improve frequency of bowel movements in those with constipation, it remains unclear whether they have any effect on pain. Osmotic laxatives such as milk of magnesia as well as nonabsorbable polyethylene glycol, sorbitol,lactulose are generally believed to be safer than stimulant laxatives, but they may be associated with bloating / flatulence; so senna / bisacodyl may be appropriate for intermittent use for constipated patients. Tegaserod, a 5-HT4 (serotonin) agonist had been previously approved to treat IBS with constipation in women& improved bowel movements, abdominal pain& global IBS symptoms. Lubiprostone, a Cl channel antagonist approved to treat chronic constipation in adults,it doesn t alleviate abd pain Treatment options for IBS-C Drug class Generic name (dose) Key points Bulking agents Osmotic laxatives Stimulant laxatives Emollient laxatives 5-HT 4 agonist Chloride channel activator Treatment for DP-IBS Psylium ( g daily in divided doses) Methylcellulose (500 mg, 1-2 tablespoons daily or up to 3 times daily) Calcium polycarbophil (1,250 mg 2 or 4 times daily) Milk of magnesia (400 mg/5ml, ml up to 4 times daily) Lactulose (10-20 g/15-30 ml daily) Polyethylene glycol (17 g in 237 ml solution daily) Senna (15 mg daily) Diphenylmethane derivatives (e.g., bisacodyl at a dose of 10 mg, 1-2 tablets daily or 1 suppository daily) Docusates (100 mg, 1-2 tablets daily) Mineral oil (5-10 cm 3 daily) Tegaserod (6 mg twice daily) Lubiprostone (8 µg twice daily with meals) May improve straining and hard stools Benefit mainly shown with psylium Used clinically for treatment of constipation but efficacy in IBS has not been well studied Used clinically for treatment of constipation but efficacy in IBS has not been well studied Used clinically for treatment of constipation but efficacy in IBS has not been studied Only available for emergency use by FDA due to reported cardiovascular risks Approved by FDA for IBS-C in women, & chronic idiopathic constipation in men & women Consider increasing dose to 24 µg twice daily if no response with lower dose In IBS with diarrhea, loperamide improved both bowel movement frequency & consistency, but it had no effect on other IBS symptoms. Alosetron, a 5-HT3 antagonist, alleviates abd pain, global IBS symptoms, & diarrhea & urgency in women & men with IBS with diarrhea; potential serious but uncommon side effects include severe constipation & ischemic colitis. It should be reserved for patients who have failed to respond to conventional therapies. Treatment options for IBS-D Drug class Generic name (dose) Key points Antidiarrheals Loperamide (1-8 mg 4 times daily in divided doses) Diphenoxylate (5 mg up to 4 times daily) Useful for the treatment of diarrhea but no global symptom relief shown Titrate dose to desired effect and avoid constipation 5-HT 3 antagonist Alosetron (0.5-1 mg twice daily) Efficacious for IBS-D Only available for treatment of severe IBS-D in women under a risk management program Concerns of serious complications of constipation and ischemic colitis Tricyclic antidepressants Amitripyline ( mg at night) Doxepin ( mg at night) Impiramine ( mg at night) Clompipramine ( mg at night) Trimipramine ( mg at night) Desipramine ( mg at night) Nortriptyline ( mg at night) Post hoc analysis of an IBS trial suggests efficacy in IBS-D Initiated at lower dose than usual dose for mood disorders Recommend titrating dose for desired effect & to minimize adverse effects Antibiotics Rifamixin ( mg three times daily) Global efficacy demonstrated in nonconstipating IBS improvement in bloating also demonstrated 4 P a g e

5 Treatment for abdominal pain Antispasmodic agents, including Mebeverine, dicyclomine, hyo-scyamine, peppermint oil, function as GIT smooth muscle relaxants. Reduce abd pain in the short term, but not well substantiated, associated with side effects that preclude their use& may cause constipation. Tricyclic antidepressants &SSRI have analgesic properties; tricyclics also have an anticholinergic effect & may induce constipation. Smaller doses than are used in the treatment of depression are generally recommended. Comorbid depression may best be treated with a SSRI. Psychosocial stressors should also be addressed. Treatment options for pain and/or bloating Drug class Generic name (dose) Key points Antispasmodics Hyoscamine sulfate (0.125 mg sublingually or by mouth up to four times daily) Dicyclomine (10-20 mg by mouth twice daily or up to four times daily) Clidinium + chlordiazepoxide (2.5 mg/5mg, 1-2 tablets up to three or four times daily) Hyoscamine + scopolamine + atropine + phenobarbital (1-2 tablets up to three or four times daily) Tricyclic antidepressants Selective serotonin reuptake inhibitors Amitripyline ( mg at night) Doxepin ( mg at night) Impiramine ( mg at night) Clompipramine ( mg at night) Trimipramine ( mg at night) Desipramine ( mg at night) Nortriptyline ( mg at night) Fluoxetine (10-40 mg daily) Citalopram (20 mg daily) Paroxetine (20-50 mg daily) Sertraline ( mg daily) Escitalopram (10 mg daily) Limited proven efficacy in IBS but may be helpful for postprandial symptoms Can be used as needed To be taken before meals Post hoc analysis of an IBS trial suggests greater efficacy in IBS-D Initiated at lower dose than usual dose for mood disorders Recommend titrating dose for desired effect and to minimize adverse effects Limited studies suggest improvement in overall well-being Large, randomized, controlled trials in IBS are needed IBS treatment options for global symptoms and/or overall well-being Treatment Key points Psychological and behavioral therapy Cognitive behavioral therapy Modifies maladaptive behaviors and thoughts Improves IBS symptoms Hypnotherapy Improves IBS symptoms Complementary alternative medicine Acupuncture Improvement in IBS symptoms has not been shown in controlled trials Placebo effects produce clinically significant improvement The patient-practitioner relationship is the most robust component of the placebo effect Chinese herbal therapy May help with improving symptoms, but no high-quality studies performed Concerns raised about possible adverse effects 5 P a g e

6 Treatment for bacterial overgrowth While the link between small intestinal bacterial overgrowth & IBS remains unclear, the short-term (10-14 days) use of the nonabsorbed antibiotic rifaximin at doses between mg/day has demonstrated improvement in global IBS symptoms, bloating &diarrhea in IBS & diarrhea. Other antibiotics such as neomycin may be effective. The efficacy of probiotics is yet to be determined adequately. Antibiotic /probiotic therapy has been used because bacterial overgrowth has been implicated, possibly through abnormal motility or as a sequela of postinfectious IBS. Rifaximin has been effective in relieving symptoms in patients with bacterial overgrowth. Bifidobacterium infantis is the only probiotic that has proven efficacy in the treatment of IBS. Key points IBS can be confidently diagnosed with symptom-based criteria in the absence of alarm signs Management of IBS involves an integrative approach, including establishment of an effective patient-provider relationship, education, reassurance, dietary alterations, pharmacotherapy aimed at the most bothersome symptoms, behavioral and psychological treatment Fiber, laxatives, a chloride channel activator and, rare, 5-HT 4 agonists are used to treat constipation-predominant symptoms Antidiarrheal agents, antibiotics, tricyclic antidepressants and, in severe cases, a 5-HT 3 antagonist are used to treat diarrhea-predominant symptoms Dietary measures, probiotics and antibiotics may be efficacious for reducing bloating and gas; antidepressants and anticholinergics can help relieve abdominal pain Effective psychological and behavioral treatment interventions for IBS include cognitive behavioral therapy, hypnosis, psychotherapy and stress management 6 P a g e

IBS Irritable Bowel syndrome Therapeutics II PHCL 430

Salman Bin AbdulAziz University College Of Pharmacy IBS Irritable Bowel syndrome Therapeutics II PHCL 430 Email:- ahmedadel.pharmd@gmail.com Ahmed A AlAmer PharmD R.S is 32-year-old woman experiences intermittent