Lecture 12 Gastrointestinal Disorders Inflammatory Bowel Disease University of Nizwa College of Pharmacy and Nursing School of Pharmacy PHARMACOTHERAPY II PHCY 410 Lecture 12 Gastrointestinal Disorders Inflammatory Bowel Disease Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

Course Outcomes Upon completion of this lecture the students will be able to Describe etiology, clinical manifestations and diagnosis of inflammatory bowel disease. Develop skills for monitoring drug therapy and patient education in patients with inflammatory bowel disease. Explain drug related problems and develop pharmaceutical care plan in patients with inflammatory bowel disease.

There are two forms of idiopathic inflammatory bowel disease (IBD): Ulcerative colitis, a mucosal inflammatory condition confined to the rectum and colon. Crohn’s disease, a transmural inflammation of GI mucosa that may occur in any part of the GI tract. PATHOPHYSIOLOGY The major theories of the cause of IBD involve a combination of infectious, genetic, and immunologic causes. Microflora of the GI tract may provide a trigger to activate inflammation.

Causes for Inflammatory Bowel Disease Infectious agents    Viruses (e.g., measles)    L-Forms of bacteria    Mycobacteria    Chlamydia Genetics    Metabolic defects    Connective tissue disorders Environmental Factors    Diet    Smoking (Crohn's disease) Immune defects    Altered host suceptibility    Immune-mediated mucosal damage Psychologic factors    Stress    Emotional or physical trauma    Occupation

ULCERATIVE COLITIS It is confined to colon and rectum and affects primarily the mucosa and submucosa (form of a crypt abscess). Minor complications include hemorrhoids, anal fissures, or perirectal abscesses. Risk of colonic carcinoma more in patients with ulcerative colitis as compared with the general population. Patients have hepatobiliary complications (fatty liver, active hepatitis, Cirrhosis) and some have arthritis, ocular, dematologic and mucosal complications. CROHN’S DISEASE A transmural inflammatory process affects terminal ileum. Fistula formation is common Systemic complications are similar to those found with ulcerative colitis. Arthritis, iritis, skin lesions, and liver disease.

Clinical Presentation of Ulcerative Colitis Signs and symptoms Abdominal cramping Frequent bowel movements, often with blood in the stool Weight loss Fever and tachycardia in severe disease Blurred vision, eye pain, and photophobia with ocular involvement. Arthritis Raised, red, tender nodules that vary in size from 1 cm to several centimeters.

Physical examination Hemorrhoids, fissures, or perirectal abscesses may be present Iritis, uveitis, episcleritis, and conjunctivitis with ocular involvement Dermatologic findings with erythema nodosum, pyoderma gangrenosum, or aphthous ulceration Laboratory tests Decreased hematocrit/hemoglobin Increased erythrocyte sedimentation rate Leukocytosis and hypoalbuminemia with severe disease

Clinical Presentation of Crohn’s Disease Signs and symptoms Malaise and fever Abdominal pain Frequent bowel movements Hematochezia (passage of fresh blood in stools) Fistula Weight loss Arthritis Physical examination Abdominal mass and tenderness Perianal fissure or fistula Laboratory tests Increased white blood cell count and erythrocyte sedimentation rate

TREATMENT Goals of treatment include resolution of acute inflammatory processes, resolution of attendant complications (e.g., fistulas, abscesses), improvement of systemic manifestations (e.g., arthritis), maintenance of remission from acute inflammation, or surgical palliation or cure. To relieve the inflammatory process. Salicylates, glucocorticoids, antimicrobials, and immunosuppressive agents are commonly used to treat active disease and, for some agents, to lengthen the time of disease remission. Surgical procedures are sometimes performed when active disease is not adequately controlled.

NONPHARMACOLOGIC TREATMENT Nutritional Support Patients are often malnourished. Nutritional needs can be adequately addressed with enteral supplementation. Patients who have severe disease may require a course of parenteral nutrition. Probiotic formulas have been effective in maintaining remission. Surgery For ulcerative colitis, colectomy may be performed when the patient has disease uncontrolled by maximum medical therapy. High recurrence rate of Crohn’s disease after surgery.

PHARMACOLOGIC THERAPY The major types of drug therapy used in IBD include aminosalicylates, glucocorticoids, immunosuppressive agents (azathioprine, mercaptopurine, cyclosporine, and methotrexate), antimicrobials (metronidazole and ciprofloxacin), and agents to inhibit tumor necrosis factor-α (TNF- α) (anti–TNF- α antibodies). Sulfasalazine, an agent that combines a sulfonamide (sulfapyridine) antibiotic and mesalamine (5-aminosalicylic acid) in the same molecule, has been used for many years to treat IBD. Corticosteroids and adrenocorticotropic hormone have been widely used for moderate to severe disease. Prednisone is most commonly used. Budesonide is an oral controlled-release formulation that minimizes systemic effects.

Immunosuppressive agents such as azathioprine and mercaptopurine (a metabolite of azathioprine) are generally reserved for cases that are refractory to steroids. They may be associated with serious adverse effects such as lymphomas, pancreatitis, or nephrotoxicity. Methotrexate given 15 to 25 mg intramuscularly once weekly is useful for treatment and maintenance of Crohn’s disease. Antimicrobial agents, particularly metronidazole, are frequently used in attempts to control Crohn’s disease, particularly when it involves the perineal area or fistulas. Infliximab is an anti-TNF antibody that is useful in moderate to severe active disease and steroid-dependent or fistulizing disease. (Adalimumab if lost response with infliximab)