clinical pharmacology GASTROENTEROLOGY IRRITABLE BOWEL SYNDROME Diagnosis of IBS The four bowel patterns of IBS The Rome III criteria Symptoms Alteration in bowel habits Visceral hypersensitivity Central neural dysregulation Alarm features IS IT IBS? Donald Zabriskie OBJECTIVES At the completion of the presentation, the participant should be able to: Describe one distinct difference in the drug treatment of versus that of inflammatory bowel disease List the major categories of drugs used for the treatment of Describe the conditions that should be present when therapy moves to the use of agents such as alosetronand the adverse drug reaction potential of this type of therapy TELL ME ABOUT IBS What is IBS? Awidespread condition involving recurrent abdominal pain and diarrhea or constipation, often associated with stress, depression, anxiety, or previous intestinal infection Who does it affect? What causes IBS? NO DRUGS? Non-pharmacologic approaches Patient counseling Psychotherapy Diet modification 1
LAXATIVES Non-standard fare Lubiprostone(Amitiza ) Chloride channel activator resulting in increased intestinal fluid secretion and intestinal motility For IBS-C in adult women Headache, nausea, diarrhea Dose 8 mcg orally twice a day DRUGS Drugs match to the symptoms For IBS-C Laxatives For IBS-D Antidiarrheals For IBS-M A combination of agents Drugs for the visceral hyperalgesia Drugs addressing abnormal serotonin pathways Agents to restore the colon environment LAXATIVES Standard fare Psyllium fiber Polyethylene glycol 3350 ( Miralax ) Calcium polycarbophil( FiberCon ) Magnesium hydroxide Lactulose Notso standard Tegaserod (Zelnorm )- see later slide ANTIDIARRHEALS Standard fare Loperamide(Imodium ) Cholestyramine resin Not so standard Alosetron(Lotronex )- see later slide 2
SEROTONIN ACTIVATION Serotonin receptor activators Alosetron(Lotronex ) for IBS-D Tegaserod(Zelnorm ) for IBS-C Activation of different serotonin receptors for different effects Availability highly regulated; not generally available outside specialty practices Alosetron- constipation, ischemic bowel Tegaserod- diarrhea, serious cardiovascular events ANTISPASMODICS Anticholinergic agents Dicyclomine( Bentyl ) Hyoscyamine( Levsin ) Blocks action of acetylcholine at parasympathetic sites in smooth muscle Inhibit the gastrocolic reflex so mealtime use important Dry mouth, blurred vision, dizziness Dose Dicyclomine 40 mg 4 times a day TOO MANY MICROBES? UNAPPROVED USE Presumes bacterial overgrowth causes IBS symptoms Rifaximin(Xifaxin ) Covers gram positive, gram negative, aerobes, anaerobes and is not absorbed systemically Superinfection including C. difficile, peripheral edema, dizziness, fatigue 3
GOING NATURAL Complementary therapy Acupuncture Weeds and seeds Rhubarb Tangerine peel Cardamom Licorice Peppermint oil Meta analysis indicates potential for IBS symptoms Use of enteric coated capsules recommended TOO FEW MICROBES? Presumes lack of microorganisms like Lactobacillus, Collinsellain GI tract Bifidobacterium infantis 35624 (Align ) Better? than placebo in relieving abdominal pain/discomfort, distension/bloating and difficult defecation Relatively safe but some GI complaints, possibility of infectious processes post use WHAT DID YOU CONCLUDE? I think I d recognize IBS I know IBS will fall into 4 subtypes For IBS-C I know what laxative I d start with and how to dose it For IBS-D I know what antidiarrheal I d start with and how to dose it 4
WHAT DID YOU CONCLUDE? For IBS gut pain I know when to use an anticholinergic and when and with whom to be careful I know which drugs need a specialist and why and I know one drug option that is unapproved for IBS I can respond to a question as to what over-the-counter preparations may help the symptoms of IBS 5