INFLAMMATORY BOWEL DISEASE : INFLAMMATORY BOWEL DISEASE By,
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.
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.
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) +
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
Frequent bowel movements
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
(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)
Peripheral arthritismore common in CD,
Ankylosing spondylitis (AS) is more common in CD than UC.
Sacroiliitis, occurs equally in UC and CD,
conjunctivitis, anterior uveitis /iritis, and episcleritis EXTRAINTESTINAL MANIFESTATIONS OF IBD : EXTRAINTESTINAL MANIFESTATIONS OF IBD HEPATOBILIARY
Hepatomegaly,Cholelithiasis is more common in CD than UC
calculi,ureteral obstruction, and fistulas.
Osteoporosis and osteomalacia from vitamin D deficiency,
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.
Advanced Drug Review