Is one of the most common chronic disorders. causing patients to seek medical treatment.

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Mark Ethelbert Turner
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2 ILOs After this lecture you should be able to : Define IBS Identify causes and risk factors of IBS Determine the appropriate therapeutic options for IBS

3 Is one of the most common chronic disorders causing patients to seek medical treatment. IBS can be defined as a functional bowel disorder characterized by abdominal pain associated with a change of bowel habit for at least 3 months (without alarm symptoms).

4 A female sex predominance of about 3:1 is evident in most epidemiologic studies of IBS. Many of the patients also have other functional disorders, such as fibromyalgia and interstitial cystitis, and psychiatric disorders, such as major depression and generalized anxiety disorder.

5 Pathophysiology

6 Factors such as psychological stress may exacerbate the disease, but they are not the cause of IBS, Findings suggest that neurotransmitter abnormalities may cause the symptoms of IBS. Of particular interest is the role of serotonin (5-HT) in the etiology of this disorder.

7 Greater than 95% of the body s 5-HT is located in the GI tract and is stored in many cells, such as enterochromaffin cells, neurons, and smooth muscle cells. Thus, these receptors have become the target of pharmaco therapeutic manipulation for IBS.

8 Another proposed pathological mechanism of IBS is altered colonic motility. Common features of IBS : Diarrhea, constipation, and abdominal bloating Patients with IBS are often categorized as having either Diarrhea predominant (IBS-D) Or Constipation predominant (IBS-C)

9 Patients with diarrhea-predominant IBS (IBS-D) have been shown to have an exaggerated response to cholecystokinin after eating, leading to increased colonic propulsions Constipation predominant IBS (IBS-C) patients tend to have fewer colonic propulsions postprandially. Patients in whom bloating is the primary symptom of IBS may have gas production from poor fermentation of carbohydrates

10 Etiology The pathogenesis of IBS is poorly understood, although consensus theories are emerging. The fact that symptoms associated with IBS can appear in up to 30% of patients who had an episode of bacterial gastroenteritis in the recent past lend credence to an infectious etiology. Recent studies have also determined that a percentage of patients diagnosed with IBS may in fact have small intestinal bacterial overgrowth.

11 Diagnosis of this disorder is particularly important as treatment may involve a simple course of antibacterials. Most IBS patients under emotional or psychological stress will report an exacerbation of their symptoms, Familial clustering of IBS patients suggests that both genetics and formative environments may play a role in the pathogenesis of this disorder. Finally, food intolerances (e.g., lactose intolerance) may be involved in the etiology of IBS or may be misdiagnosed as IBS.

12 Diagnosis One of the more challenging and frustrating aspects of IBS is its lack of biochemical or physical markers that are pathognomic for the disorder. The laboratory or imaging extensive testing in IBS patients is usually unnecessary provided that patients are younger than 50 years and do not present with any so-called alarm symptoms.

14 Once IBS is diagnosed, it should be further differentiated by symptom pattern into IBS-D, IBS-C, or mixed IBS (IBS-M). Small intestinal bacterial overgrowth or celiac sprue may be tested for in selected patients, but routine screening in not currently recommended. Because there is no known cure for IBS, it is logical to use these subgroups to help direct symptomatic therapy. IBS is generally considered a benign disease with a good prognosis.

15 Management Patient Education Clinicians must reassure patients with IBS that their symptoms are real. patients should be thoroughly counseled concerning the prognosis of IBS. Many patients are fearful that their symptoms are indicative of severe pathology such as cancer.

16 Reassurance and education are vital to assuage fears and to reinforce the generally benign nature of this disorder. Some patients exhibit a phenomenon known as somatization. This is defined as a tendency to experience and communicate somatic distress in response to psychosocial stress and is a factor in how often IBS patients seek health care for their condition.

17 Psychological disorders are present in a large segment of IBS patients. Treatment of comorbid disorders, including the discovery of a history of physical or sexual abuse (and possible posttraumatic stress disorder), is an important component in successfully treating IBS.

18 Diet Food intolerance may cause symptoms similar to those associated with IBS. Patients with lactose intolerance can experience pain, bloating, and diarrhea after ingesting milk-based products. A dietary and symptom diary may reveal such an intolerance, and avoidance of the implicated foods would constitute effective treatment.

19 Treatment guidelines conditionally recommend an increase in dietary fiber (e.g., wheat bran up to 20 g daily) as a reasonable first-line treatment for IBD-C. Patients should be counseled that large doses of fiber can lead to abdominal gas and bloating.

20 Diagnosis of IBS

21 Pharmacotherapy for Constipation- Predominant IBS 1) laxatives: In patients with IBS-C in whom fiber therapy fails, other standard laxatives may be tried for symptomatic relief. These may include : - Milk of magnesia. - Lactulose. - Senna. - Or polyethylene glycol without electrolytes. This last agent was shown to improve the number of bowel movements, but had no effect on abdominal pain or bloating. Usually well tolerated, although they can occasionally cause abdominal bloating.

22 Other adverse effects of the osmotic laxatives include: - diarrhea. - Taste disturbances. - Hypermagnesemia (especially in patients with renal impairment). If the pt have low cost and the lack of contraindications, milk of magnesia 15 ml daily is a reasonable first treatment. 2) TEGASEROD: The first of these agents, was originally approved in the United States for women with IBS-C. Was evaluated in women with at least a 3-month history of IBS-C symptoms. Unfortunately, post marketing analysis by the US Food and Drug Administration found an increased incidence of heart attack, stroke, and unstable angina in patients receiving the drug So, the manufacturer of tegaserod halted all sales and marketing of this agent.

3) LUBIPROSTONE: (chloride-channel activator) That enhances intestinal fluid secretion and acts as a laxative, was approved in the United States for IBS-C in women older than 18 years of age.

23 3) LUBIPROSTONE: (chloride-channel activator) That enhances intestinal fluid secretion and acts as a laxative, was approved in the United States for IBS-C in women older than 18 years of age. The Dose: is 8 mcg orally twice daily, which is a lower dose than used for chronic idiopathic constipation. The drug was moderately effective in improving patient perception of constipation symptoms. Primary adverse effects include: Nausea and vomiting ameliorated by taking the medication with food. can be somewhat Because the drug is associated with teratogenic effects in animals, the manufacturer recommends that women who could become pregnant have a negative pregnancy test before beginning therapy and be able to comply with effective contraceptive measures during therapy. The drug is significantly more expensive than traditional laxatives, and should generally be reserved for patients who have failed other therapy for IBS-C.

Irritable Bowel Syndrome Associated Pain and Bloating 1) ANTISPASMODICS: Drugs that possess smooth muscle relaxation properties, usually by anticholinergic pathways, have long been used to treat IBS

24 Irritable Bowel Syndrome Associated Pain and Bloating 1) ANTISPASMODICS: Drugs that possess smooth muscle relaxation properties, usually by anticholinergic pathways, have long been used to treat IBS The Two Most commonly prescribed antispasmodics are hyoscyamine and dicyclomine. Current treatment guidelines list antispasmodics as options for antispasmodic drugs for pain or bloating associated with IBS If prescribed, an as-needed strategy of use. Peppermint oil capsules also have smooth muscle relaxation properties and have been shown to be beneficial in IBS-related pain and cramping in several studies.

25 2) ANTIDEPRESSANTS: Current treatment guidelines recommend the use of either tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs) for patients with severe or continuous abdominal pain. found low-dose tricyclic antidepressants significantly improved pain, bloating, and IBS symptoms compared with placebo. low doses of tricyclic antidepressants ( e.g., Amitriptyline: mg at bedtime) are often effective in relieving abdominal pain and diarrhea. Secondary amine tricyclic antidepressants (nortriptyline, desipramine) are better tolerated by many patients than tertiary amines (amitriptyline, imipramine) owing to decreased anticholinergic adverse effects such as : gain. sedation, dry mouth and eyes, urinary retention, and weight DOSE of Nortriptyline: 10mg orally at bedtime should be initiated with titration to symptom relief and lack of adverse effects. SSRI use is more controversial in IBS patients as conclusive evidence of efficacy is lacking. A recent pilot study suggested that duloxetine may improve pain and

Diarrhea-Predominant Irritable Bowel Syndrome 1) STANDARD ANTIDIARRHEALS: Loperamide, an opioid agonist that penetrates poorly into the central nervous system, is the preferred agent for IBS-D.

26 Diarrhea-Predominant Irritable Bowel Syndrome 1) STANDARD ANTIDIARRHEALS: Loperamide, an opioid agonist that penetrates poorly into the central nervous system, is the preferred agent for IBS-D. Have an effective agent for improving diarrhea. As with the antispasmodics, as-needed treatment is preferred to scheduled dosing (e.g., 2 4 mg PO up to four times daily as needed). Prophylactic dosing before a stressful situation or an event during which bathroom access is limited is particularly effective. Diphenoxylate with atropine is generally considered a second-line agent because of its increased risk of anticholinergic adverse effects. cholestyramine is occasionally used in refractory cases of IBS-D, especially when bile acid malabsorption is suspected or confirmed AND also has a significant number of drug interactions of which the clinician

27 2)ALOSETRON: Is a highly potent 5-HT3 receptor antagonist that slows colonic transit time, increases intraluminal sodium absorption, and decreases small intestinal secretions. DOSE: is 0.5 mg BID for 1 month. If, after 4 weeks, this is well tolerated but does not adequately control IBS symptoms, then the dosage can be increased to 1mg BID. It is imperative that patients not start alosetron if they have a history of problems with constipation, bowel obstruction or ischemic colitis, Inflammatory bowel disease (IBD),or a thromboembolic disorder. Prescribers Must Registered with the drug manufacturer, and patients must sign a patient physician agreement and be provided with a written medication guide. Patients must immediately discontinue alosetron if they become constipated or have symptoms of ischemic colitis, such as new or worsening abdominal pain, bloody diarrhea, or blood in the stool.

28 EMERGING THERAPIES The nonabsorbable antibiotic rifaximin had been shown in two small studies to improve global symptoms in IBS for up to 10 weeks. Treatment guidelines suggest that a course of rifaximin (400 mg BID for 10 days) may be reasonable in IBS patients, particularly those with IBS-D. If her symptoms worsen or her current regimen lose effectiveness, a course of rifaximin would be considered an alternative strategy.

29 FOR YOUR ATTENTION

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