7/2/2020 Guts and Butts: Treatment Options for IBS and Functional Dyspepsia Amy McCracken, DNP, APRN 1 Learning Objectives: ● Discuss the diagnosis and management of IBS and functional dyspepsia in order to optimize treatment strategies ● Describe pharmacological and alternative treatment approaches of IBS-C, IBS-D, IBS-M, and functional dyspepsia ● Articulate patient-specific treatment options for those with IBS and functional dyspepsia as derived from case studies 2 1 7/2/2020 Irritable Bowel Syndrome (IBS)-Definition and Epidemiology ● Comprises a group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habits in the absence of an organic disease. ● The prevalence of IBS in North America is estimated at approximately 10-15%. ● More common in women compared to men. ● Second highest cause of work absenteeism ● IBS accounts for approximately 25 to 50% of all referrals to gastroenterologists. ● Important to remember: This is a diagnosis of exclusion! 3 IBS-Etiology ● Stress ● Visceral hypersensitivity ● Psychosocial factors ● Common-cannot be explained ● Chronic and benign ● High association with stress in the pathophysiology and clinical presentation of IBS 4 2 7/2/2020 IBS-Signs and Symptoms ● Chronic abdominal pain-usually a cramping sensation that varies in intensity with periodic exacerbations ● The character and location of pain can vary widely and often times related to defecation ● Abdominal fullness, bloating or swelling ● Diarrhea, constipation or alternating diarrhea and constipation or normal bowel habits alternating with either diarrhea and/or constipation ● Feeling of incomplete evacuation ● Mostly during waking hours 5 IBS-Atypical Signs and Symptoms The following atypical signs and symptoms should prompt further evaluation for organic disease: ● Acute onset of symptoms or onset of symptoms after age 50 ● Fever ● Rectal bleeding or anemia ● Weight loss ● Persistent diarrhea ● Severe constipation ● Nocturnal symptoms ● Abnormal colonoscopy ● Family history of GI cancer, IBD, or celiac disease 6 3 7/2/2020 IBS-Diagnosis ● IBS is a diagnosis of exclusion ● ROME IV criteria for IBS: Defined as recurrent abdominal pain, on average, at least one day per week in the last three months, associated with two or more of the following: ○ Relieved with defecation; and/or ○ Onset associated with a change in frequency of stool ○ Onset associated with change in the form of stool (appearance) 7 IBS Subtypes ● IBS with predominant constipation (IBS-C): Abnormal bowel movements are usually constipation ● IBS with predominant diarrhea (IBS-D): Abnormal bowel movements are usually diarrhea ● IBS with mixed bowel habits (IBS-M): Abnormal bowel movements are usually both constipation and diarrhea (at least ¼ of each) ● IBS unclassified: Diagnostic criteria met, but cannot be categorized into one of the other three subtypes 8 4 7/2/2020 Differential Diagnosis ● If diarrhea predominant: celiac disease, microscopic colitis, small intestinal bacterial overgrowth, fructose/lactose/sucrose intolerance, inflammatory bowel disease (IBD), bile salt malabsorption ● If constipation predominant: organic disease, dyssynergic defecation ● Always review medication profile as a potential cause for constipation or diarrhea (psychotropic medications, oral hypoglycemic agents, thyroid replacement therapy, iron supplements, narcotics) 9 Initial Evaluation of IBS ● Detailed H&P: medication exposure; recent acute viral or bacterial gastroenteritis; family history of IBD, colon cancer, celiac disease ● Lab work: ○ CBC to evaluate for anemia ○ In patients with constipation: TSH and calcium (or ionized calcium) ○ In patients with diarrhea: Fecal calprotectin or CRP, stool studies, serologic testing for celiac disease ● Colorectal cancer screening if age appropriate ● Abdominal imaging in patients with constipation ● Anorectal manometry in patients with severe constipation refractory to management with dietary changes and osmotic laxative therapy 10 5 7/2/2020 IBS-Treatment ● Initial Therapy ○ Lifestyle and dietary modification in patients with mild and intermittent symptoms that do not impair quality of life ○ Dietary modification: low FODMAP (fermentable oligo-, di-, and monosaccharides and polyols), lactose free diet, gluten free diet ○ Fiber ○ Food allergy testing and breath testing ○ Physical activity 11 IBS Treatment-Fiber ● Role of fiber is controversial, but no serious side effects, so should be considered in patients with IBS whose predominant symptom is constipation ● Primarily exert their laxative effect by absorbing water and increasing fecal mass ○ Psyllium based fiber: contains 70% soluble fiber, so can cause increased fullness/bloating/gas and slow digestion ■ Examples: Metamucil, Konsyl ○ Insoluble based fiber (Methylcellulose): nonfermentable, so less likely to contribute to bloating and gas ■ Example: Citrucel (gluten free) ○ Calcium Polycarbophil (Fibercon) and Wheat dextrin (benefiber) 12 6 7/2/2020 IBS-C Pharmacologic Treatment Options ● Osmotic Laxatives-Polyethylene glycol (PEG), Lactulose, Magnesium Citrate ● Stimulant Laxatives-Bisacodyl, Senna ● Secretagogue- ○ Lubiprostone (Amitiza) ○ Linaclotide (Linzess) ○ Plecanatide (Trulance) 13 Osmotic Laxatives ● Examples: Polyethylene Glycol (PEG), Lactulose, Milk of Magnesia, Magnesium Citrate ● Mechanism of Action: Cause intestinal water secretion and thus increase stool frequency ● Side Effects: Excessive use may result in electrolyte imbalances and volume overload in patients with renal or cardiac disease ● Polyethylene Glycol (Miralax) ○ Inexpensive, few side effects ○ Improves constipation, but not abdominal pain or severity of bloating ○ Initially start with 17 g of powder dissolved in 8 oz of water (other liquid) daily ○ Titrate up or down to a maximum of 34 g daily ○ Important to educate the patient on proper use and titration 14 7 7/2/2020 Osmotic Laxatives, Cont ● Lactulose ○ Synthetic disaccharide-not metabolized by intestinal enzymes, so water and electrolytes remain within the intestinal lumen due to the osmotic effect of the digested sugar ○ Requires 24-48 hours to achieve its effect ○ May cause bloating and flatulence ● Milk of Magnesia/Magnesium Citrate ○ Poorly absorbed and act as hyperosmolar solutions ○ May cause hypermagnesemia, especially in patients with renal impairment 15 Stimulant Laxatives ● Examples: Bisacodyl (Dulcolax), Senna (Senokot) ● Mechanism of Action: ○ Cause alteration of electrolyte transport by the intestinal mucosa ○ Increase intestinal motor activity ● Side Effects: ○ Prolonged daily ingestion may be associated with hypokalemia, protein losing enteropathy and salt depletion ○ Long term safety has not been established 16 8 7/2/2020 Secretagogue ● Examples: Lubiprostone (Amitiza), Linaclotide (Linzess), Plecanatide (Trulance) 17 Lubiprostone-Amitiza ● Mechanism of Action: ○ Locally acting chloride channel activator that enhances chloride-rich intestinal fluid secretion, thus secreting chloride and water into the gut lumen ● Side Effects: ○ Long term safety has not been established ○ Most common adverse event was nausea; followed by diarrhea and headache ● Used for treatment of IBS-C in women age 18 years and older, but can also be used in men; should discontinue use with pregnancy ● The approved dose for IBS-C is 8 mcg twice daily (the approved dose for treatment of chronic idiopathic constipation is 24 mcg twice daily) 18 9 7/2/2020 Linactolide-Linzess ● Mechanism of Action: ○ Guanylate cyclase agonist that stimulates intestinal fluid secretion and transit ○ May decrease visceral pain by reducing pain sensing nerve activity ● Side Effects: ○ The most common side effect is diarrhea (16-22%); Discontinue use if diarrhea is severe ○ Contraindicated in pediatric patients under the age of 6 and safety has not been established in patients younger than 18 ● The approved dose for IBS-C is 290 mcg daily (the approved dose for treatment of chronic idiopathic constipation is 145 mcg daily or 72 mcg daily) ● Administer 30 minutes prior to the first meal of the day on an empty stomach (loose stools and greater stool frequency can occur if taken with a high fat breakfast) ● Can be used with pregnancy 19 Plecanatide-Trulance ● Mechanism of Action: ○ Guanylate cyclase agonist that stimulates intestinal fluid secretion and transit ● Side Effects: ○ May cause diarrhea during the first month of use (severe diarrhea during the first 3 days of use); discontinue use if diarrhea is severe or dehydration occurs ● The approved dose for IBS-C (and chronic idiopathic constipation) is 3 mg once daily ● Can be taken with or without food ● Can be used with pregnancy 20 10 7/2/2020 IBS-D Pharmacologic Treatment Options ● Antidiarrheal agents-Loperamide ● Bile acid sequestrants-Cholestyramine (Questran)/Colestipol (Colestid)/Colesevelam (Welchol) ● 5-hydroxytryptamine (serotonin) 3 receptor antagonists (5HT-3)-Alosetron (Lotronex) ● Eluxadoline (Viberzi) 21 Antidiarrheal Agents ● Example: Loperamide (Imodium) ● Mechanism of Action: ○ Acts directly on circular and longitudinal intestinal muscles, through the opioid receptor, to inhibit peristalsis and prolong transit time ○ Decreases stool frequency and consistency; increases anal sphinter tone ● Side Effects: ○ Constipation (2-5%), abdominal cramps and nausea (<3%) ● Should be used as the initial treatment of IBS-D ● Typically will not treat symptoms of bloating, abdominal discomfort or global IBS symptoms ● Dosing: 4 mg after first loose stool, followed by 2