INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE By, Mohammed Rafi 1st year M.Pharm Department of Pharmacy practice


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE Definition : Idiopathic inflammatory bowel disease is a set of chronic inflammatory condition resulting from inappropriate and persistent activation of the mucosal immune system, driven by the presence of normal intraluminal flora.


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE The two disorders known as inflammatory bowel disease are : Ulcerative colitis (UC) Crohn’s disease (CD) Both CD and UC are chronic, relapsing inflammatory disorders of obscure origin.


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE UC is a chronic inflammatory disease limited to the colon and rectum. CD is an autoimmune disease that may affect any portion of the gastrointestinal tract from esophagus to anus. Both exhibit extra intestinal inflammatory manifestations.


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE ETIOLOGY : In IBD the state of homeostasis is disrupted, leading to two key pathogenic abnormalities : Strong immune responses against normal flora, and Defects in epithelial barrier.


Proposed Etiologies for Inflammatory Bowel Disease :Proposed Etiologies for Inflammatory Bowel Disease Infectious agents :   Viruses (e.g., measles)   L-Forms of bacteria   Mycobacteria   Chlamydia Genetics :   Metabolic defects   Connective tissue disorders


Proposed Etiologies for Inflammatory Bowel Disease :Proposed Etiologies for Inflammatory Bowel Disease Environmental Factors :   Diet   Smoking (Crohn's disease) Immune defects :   Altered host suceptibility   Immune-mediated mucosal damage Psychologic factors :    Stress   Emotional or physical trauma   Occupation


PATHOPHYSIOLOGY :PATHOPHYSIOLOGY In both UC and CD, activated CD4+ T cells in the lamina propria and peripheral blood secrete inflammatory cytokines. CD4 + T cells are of two major types, TH 1 cells [interferon (IFN), tumor necrosis factor (TNF)] and TH 2 cells (IL-4, IL-5, IL-13).


PATHOPHYSIOLOGY :PATHOPHYSIOLOGY TH 1- cells appear to induce transmural granulomatous inflammation that resembles CD, and TH 2 cells appear to induce superficial mucosal inflammation resembling UC. The exaggerated T-cell response in both conditions leads to intestinal damage and increased permeability


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE ULCERATIVE COLITIS : Ulcerative colitis is an idiopathic chronic inflammatory disease of the colon and rectum, characterized by mucosal inflammation and typically presenting with bloody diarrhea.


SIGNS AND SYMPTOMS :SIGNS AND SYMPTOMS Abdominal cramping Frequent bowel movements, often with blood in the stool. Weight loss Arthritis Fever and tachycardia in severe disease


SIGNS AND SYMPTOMS :SIGNS AND SYMPTOMS Blurred vision, eye pain, and photophobia with ocular involvement Physical examination : Hemorrhoids, and fissures, or perirectal abscesses may be present Iritis, uveitis, episcleritis, and conjunctivitis with ocular involvement


SIGNS AND SYMPTOMS :SIGNS AND SYMPTOMS 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


SEROLOGICAL TESTS :Two antibodies that can be detected in the serum of IBD patients are ; perinuclear antineutrophil cytoplasmic antibodies (pANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCAs). A distinct set of antineutrophil SEROLOGICAL TESTS


SEROLOGICAL TESTS :pANCA positivity is found in about 60 to 70% of UC patients and 5 to 10% of CD patients; ASCA antibodies recognize mannose sequences in the cell wall mannan of S. cerevisiae; 60 to 70% of CD patients, 10 to 15% of UC SEROLOGICAL TESTS


TREATMENT : :TREATMENT : The first line of drug therapy for the patient with mild to moderate colitis. Oral Sulfasalazine :– 500 mg/day ,4 g/day upto 8g/day maximum tolerated. or an oral Mesalamine:- 2-4.8g/day or topical Mesalamine :- 4g every 1-2day or Prednisolone :- 1 mg/kg/day


TREATMENT : :TREATMENT : Continuous intravenous infusion of Cyclosporine (4 mg/kg/day) for acute severe ulcerative colitis refractory to steroids For maintenance of remission Sulfasalazine (2 g/day) + Mesalamine derivatives. Azathioprine is effective in preventing relapse of ulcerative colitis for periods of up to 2 years.


Slide 21:Source :Pharmacotherapy Handbook, 6th Edition ,, DiPiro


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE CROHN DISEASE : First described by Crohn,Ginsburg and Oppenheimer in 1932. Crohn’s disease is characterized by transmural inflammation of the gut wall and can affect any part of the tubular GI tract.


SIGNS AND SYMPTOMS :SIGNS AND SYMPTOMS Malaise and fever Abdominal pain Frequent bowel movements Hemotachezia Fistula Weight loss Arthritis


SIGNS AND SYMPTOMS :SIGNS AND SYMPTOMS Physical examination : Abdominal mass and tenderness Perianal fissure or fistula Laboratory tests : Increased white blood cell count and erythrocyte sedimentation rate


TREATMENT :TREATMENT Sulfasalazine Mesalamine derivatives, or Steroids -Prednisolone Azathioprine, Mercaptopurine-Methotrexate Metronidazole (given orally up to 20 mg/kg/day)


Slide 28:Source :Pharmacotherapy Handbook, 6th Edition ,, DiPiro


TREATMENT :TREATMENT NEW THERAPIES IN CD : Methotrexate - for maintenance Chimeric monoclonal AB cA2 (Infliximab) Interleukin-10


EXTRAINTESTINAL MANIFESTATIONS OF IBD :EXTRAINTESTINAL MANIFESTATIONS OF IBD DERMATOLOGIC Erythema nodosum (EN) Pyoderma gangrenosum (PG) RHEUMATOLOGIC Peripheral arthritismore common in CD, Ankylosing spondylitis (AS) is more common in CD than UC. Sacroiliitis, occurs equally in UC and CD, OCULAR conjunctivitis, anterior uveitis /iritis, and episcleritis


EXTRAINTESTINAL MANIFESTATIONS OF IBD :EXTRAINTESTINAL MANIFESTATIONS OF IBD HEPATOBILIARY Hepatomegaly,Cholelithiasis is more common in CD than UC UROLOGIC calculi,ureteral obstruction, and fistulas. OTHER Osteoporosis and osteomalacia from vitamin D deficiency, calcium malabsorption, cardiopulmonary manifestations include endocarditis,myocarditis, pleuropericarditis, and interstitial lung disease.


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE References ; Title: Pharmacotherapy Handbook, 6th Edition, : DiPiro, Joseph T.; Harrison’s Principal of Internal Medicine 16th ed. IDR MedClik. CIMS Asia. Advanced Drug Review