PHRD5985 Pharmacotherapy Lecture 4 - Inflammatory Bowel Disease

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daynuhmay
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PHRD5985 Pharmacotherapy Lecture 4 - Inflammatory Bowel Disease
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2014-02-05 03:55:21
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pharmacotherapy ibd
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pharmacotherapy ibd
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  1. 2 types of inflammatory bowel disease
    • 1) ulcerative colitis
    • 2) Crohn's disease
  2. pathophysiology of IBD
    Ag-driven inflammatory response
  3. most common location of UC occurrence
    rectum & lower colon
  4. most common location of Crohn's disease occurrence
    ileum (end of small intestine)
  5. tissue layer affected by UC
    mucosa (rarely below)
  6. characterization of UC inflammation
    continuous inflammation throughout affected area
  7. disease affecting majority of colon
    pancolitis
  8. tissue layer(s) affected by Crohn's disease
    can penetrate all layers through the bowel wall (mucosa, submucosa, muscularis, serosa)
  9. penetration through bowel wall into other organs
    fistula
  10. characterization of Crohn's disease inflammation
    • "cobblestoning" - unequal inflammation throughout 
    • polyps
  11. cause of growth retardation in Crohn's
    large amount of nutrition is absorbed at the ileum -> inflammation prevents absorption
  12. perianal disease: UC vs Crohn's
    • UC has none
    • common in Crohn's
  13. 4 levels of disease severity
    • 1) mild
    • 2) moderate
    • 3) severe
    • 4) fulminant
  14. 4 therapeutic goals of IBD treatment
    • 1) induce/maintain remission
    • 2) resolve complications
    • 3) alleviate systemic sx
    • 4) improve QOL
  15. drug treatment options for IBD (6)
    • 1) 5-aminosalicylates (5-ASA)
    • 2) antibiotics
    • 3) corticosteroids
    • 4) immunomodulators
    • 5) biological response modifiers (-mab's)
    • 6) adjunctive therapies
  16. 3 things to assess to start treatment
    • 1) which disease (UC vs CD)
    • 2) severity
    • 3) extent/location of disease
  17. adjunctive therapies for IBD (2)
    • 1) loperamide (Imodium)
    • 2) antispasmodics 

    THESE DON'T TREAT THE DISEASE
  18. antispasmotic drugs (2)
    • 1) dicyclomine
    • 2) hyocyamine
  19. mesalamine
    • 5-aminosalicylate 
    • treats mild to severe UC, mild to moderate CD
    • mostly topical effects (has to be delivered to site of action)
  20. patients to avoid treating w/ sulfasalazine
    sulfa allergic
  21. non-sulfa 5-ASA drugs (3)
    • 1) mesalamine
    • 2) olsalazine
    • 3) balsalazide
  22. formulation if disease located in colon
    oral
  23. formulation if disease located in descending colon (INCLUDING splenic flexure) & rectum
    enema
  24. formulation if disease located in rectum
    suppository
  25. type of agents superior for distal disease
    topical 5-ASA agents
  26. if IBD unresponsive to 5-ASA, next line treatment
    corticosteroids
  27. only corticosteroid that is indicated as 1st line treatment of mild-moderate IBD
    budesonide
  28. MOA of immune modulating drugs
    purine antagonists
  29. drug class of azathioprine & 6-mercaptopurine
    immune modulators
  30. indicated for immune modulating drugs
    used to wean patients off steroid dependency
  31. MOA of methotrexate
    folate antagonist
  32. indications for methotrexate
    mod/severe Crohn's disease
  33. immuno modulator onset of action
    3-15 MONTHS
  34. chimeric mAb targeting TNF
    indicated for mod/severe IBD
    ***very effective for fistulizing CD***
    infliximab (Remicade)

    only available as IV
  35. recombinant IgG to TNF
    indicated for mod/severe IBD in pts resistant to other tx
    adalimumab (Humira)
  36. PEG + chimeric Fab (fragmetn of humanized TNF inhibitor mAb) against TNF
    certolizumab (Cimzia)
  37. - humanized mAb against 4-integrin 
    - interferes w/ leukocyte adhesion
    - indicated for mod/severe CD after failure of all other therapies
    - has black box warning
    natalizumab (Tysabri)
  38. first biologic agent to start pt off with
    inflixmab (Remicade)
  39. indications for antibiotic use in IBD
    • typically used only in CD
    • more effective for ileocolitis & colitis than isolated small bowel disease
    • usually in combo w/ 5-ASA
  40. abx used in CD treatment (2)
    • 1) metronidazole
    • 2) ciprofloxacin
  41. alternative therapy used short-term for steroid refractory UC or Crohn's and/or fistulizing Crohn's disease
    cyclosporine
  42. improves symptoms in patients with UC, but exacerbates them in Crohn's
    smoking/nicotine patches

    **DO NOT RECOMMEND FOR PATIENTS WITH CD***
  43. mild UC treatment
    • 5-ASAs (any formulation)
    • CCS enema
  44. moderate UC treatment
    5-ASAs, CCS enema PLUS oral CCS

    (may add immune modulator or infliximab if no response)

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