1 / 33

Inflammatory Bowel Diseases

Inflammatory Bowel Diseases. Dr. Nematollah Ahangar Assistant Prof. of Pharmacology. Definition . Two idiopathic forms ulcerative colitis: mucosal inflammatory condition confined to the rectum and colon Crohn’s disease: transmural inflammation of GI mucosa

marli
Télécharger la présentation

Inflammatory Bowel Diseases

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Inflammatory Bowel Diseases Dr. Nematollah Ahangar Assistant Prof. of Pharmacology

  2. Definition • Two idiopathic forms • ulcerative colitis: • mucosal inflammatory condition • confined to the rectum and colon • Crohn’s disease: • transmuralinflammation of GI mucosa • may occur in any part of the GI tract • The etiologies: unknown, but may have a common pathogenetic mechanism

  3. PATHOPHYSIOLOGY • combination of infectious, genetic, and immunologic causes • Microflora of the GI tract may provide a trigger to activate inflammation • Crohn’s disease may involve a T lymphocyte disorder that arises in genetically susceptible individuals • Smoking appears to be protective for ulcerative colitis but associated with increased frequency of Crohn’s disease

  4. Ulcerative colitis and Crohn’s disease differ in two general respects: anatomic sites and depth of involvement within the bowel wall

  5. fibrosis and strictures or, alternatively, fistula formation in CD

  6. Comparisons • CD: marked infiltration of lymphocytes and macrophages, granuloma formation, and submucosal fibrosis • UC: lymphocytic and neutrophilic infiltrates • CD: interleukin-12 (IL-12), interferon-γ, and tumor necrosis factor-a (TNF-α), and T-helper 1 (TH1) • UC: T-helper 2

  7. Aminosalicylates • Sulfasalazine • Olsalazine • Balsalazide • Various forms of mesalamine

  8. Mesalamine Compounds • To deliver it to different segments of the small or large bowel • Pentasa • Asacol • Rowasa • Canasa

  9. Pharmacokinetics & Pharmacodynamics • 5-ASA is readily absorbed from the small intestine • Absorption of 5-ASA from the colon is extremely low • 10% of sulfasalazine and less than 1% of balsalazide are absorbed • Sulfapyridine is absorbed from the colon • Mechanisms

  10. Clinical Uses • Induce and maintain remission in ulcerative colitis • considered to be the first-line agents for treatment of mild to moderate active ulcerative colitis • Efficacy in Crohn's disease is unproven • Effectiveness : depends in part on achieving high drug concentration at the site of active disease • suppositories or enemas are useful in patients with ulcerative colitis or Crohn's disease confined to the rectum (proctitis)

  11. Adverse Effects • Sulfasalazine: systemic effects of the sulfapyridine molecule • Individual differences of sulfasalazine AEs • nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise • Hypersensitivity to sulfapyridine • Oligospermia • Impairs folate absorption and processing • Dietary supplementation with 1 mg/d folic acid is recommended

  12. Adverse Effects • Other aminosalicylate formulations are well tolerated • Olsalazine :a secretory diarrhea in 10% of patients • Rare cases of interstitial nephritis • Rarely cause worsening of colitis

  13. Corticosteroids • have been widely used for the treatment of ulcerative colitis and Crohn’sdisease • For moderate to severe disease • Prednisoloneis most commonly used • once-daily dosing • 40–60 mg/d • After 1–2 weeks, the dosage is tapered to minimize development of adverse effects • In severely ill patients, the drugs are usually administered intravenously • Hydrocortisone enemas, foam, or suppositories (15–30% of the administered dosage is still absorbed) • Budesonidecontrolled-release formulation

  14. Ulcerative Colitis • First line • mild to moderate colitis is oral sulfasalazine • or an oral mesalaminederivative • or topical mesalamine • or steroids for distal disease • Prednisone up to 1 mg/kg/day or 40 to 60 mg daily • Steroids and sulfasalazine appear to be equally efficacious • Choice of formulation • Transdermalnicotine improved symptoms of patients with mild to moderate active ulcerative colitis

  15. Severe or Intractable Disease • Requiring hospitalization • parenteral steroids and surgical procedures • Colectomy • Continuous IV infusion of cyclosporine (4 mg/kg/day) is recommended for patients with acute severe ulcerative colitis refractory to steroids

  16. Maintenance of Remission • The major agents: sulfasalazine (2g/day) and the mesalamine derivatives • Steroids do not have a role in the maintenance of remission • Azathioprine is effective in preventing relapse of ulcerative colitis for periods exceeding 4 years

  17. Crohn’s Disease • The goal of treatment for active Crohn’s disease is to achieve remission • sulfasalazine, mesalaminederivatives, or steroids, azathioprine, mercaptopurine, methotrexate, infliximab, and metronidazole • Steroids are frequently used • Metronidazole (given orally up to 20 mg/kg/day) in some patients with colonic or ileocolonic involvement • Combination of metronidazole with ciprofloxacin

  18. Other drugs • Cyclosporine: not recommended except for patients with symptomatic and severe perianal or cutaneous fistulas • Methotrexate: given as a weekly injection of 5 to 25 mg

  19. Anti- TNFs • Infliximab, adalimumab, and certolizumab • Infliximab: IV • adalimumab, and certolizumab: SC • Injections: weekly • For the acute and chronic treatment of patients with moderate to severe Crohn's disease • Infliximab: also for UC • The median time to clinical response is 2 weeks

  20. Adverse Effects • in up to 6% of patients • infection due to suppression of the TH1 inflammatory response • Antibodies to the antibody • Acute adverse infusion reactions • myalgia, arthralgia, jaw tightness, fever, rash, urticaria, and edema • Lymphoma

  21. Anti-Integrin Therapy • Natalizumab • humanized IgG4 monoclonal antibody targeted against the α4 subunit of integrins • significant efficacy for a subset of patients with moderate to severe Crohn's disease And multiple sclerosis • 300 mg every 4 weeks by intravenous infusion • 50% of patients respond to initial therapy with natalizumab • infusion reactions and a small risk of opportunistic infections • multifocal leukoencephalopathy due to reactivation of a human polyomavirus

  22. Thanks for your attention

More Related