Gastrointestinal & endocrine pharmacology 2

Inflammatory bowel disorder
1. Crohn's disease
  1. Fever, diarrhoea, abdominal pain, rectal bleeding, abdominal mass, perianal disease-site: colon,ileum,jejunum,stomach,oesophagus=FISTULAS & CANCER
    1. Genetic associations (polymorphisms)
    2. smoking=increased risk
2. Ulcerative colitis
  1. Fever, diarrhoea, abdominal pain,rectal bleeding-site: colon=INTESTINAL CANCER
    1. smoking protects against it
Gut mucosa & bacteria
1. epithelial cells in contact with bacteria-epithelial cells form physical barrier to prevent them from getting into circa
  1. exits in state of controlled physiological inflammation
    1. delicate eqm between gut microbes,GIT physical barriers(epithelial cells etc),innate immune system that processes & present antigen to adaptive immune
      1. adaptive immune tells it not to react against them=IMMUNOLOGICAL TOLERANCE
        An inappropriate response to the presence of enteric antigens=IBD (immune response against GI bacteria)
        dendritic cells pick up antigen=T cell proliferation
        pathogenesis
        Teff (activates macrophages=inflammation)
        TH1= IFN-y & TNFa
        CD associated with TG1 cytokine profile
        TH2= IL-4 & IL-13
        UC associated with TH2 cytokine profile
        Cytokines start to damage gut cells
        Treg
        secretes TGF-b & IL-10= -ve effect on pro inflammatory cytokines
  2. APCs can allow some bacteria to get across epithelium to immune system
Treatment of IBD
1. Antiinflammatory
  1. 1. Aminosalicylates
    1. block prstaglandin production, inhibit inflammatory leukotriene syn,inhibit neutrophil chemotaxis-stop progression of inflammation
    2. 5-aminosalicylic acid/ Sulfasalazine (broken down to 5-ASA)/ Olsalazine/ Balsalazide
    3. route of admin to be considered, indicated to maintain remission, need to decrease inflammation then these drugs maintain it
  2. 2. Corticosteroids
    1. Hydrocortisone, Prednisone, Budesonide
    2. increased lipocortin production, inhibit PLA2, decreased COX induction, decreased PG, PAF syn, decreased cytokine production
      1. decreased T cell activation & proliferation, inhibit neutrophil chemotaxis
        Adverse effect=Crushings syndrome
2. Immuno-suppressant regulatives
  1. Methotrexate-inhibits purine syn/ Azothioprine & Mercaptopurine=DNA damage/cyclosporin A=interact with calcineurin needed for T cell activation=inhibi
  2. Anti-TNF (infliximab)=targets secreted & cell bound TNF-blocks its effects on macrophages-adverse effects=reactivation of tuberculosis,lymphomas
3. Antibiotics/Probiotics
  1. Metronidazole, Ciprofloxacin, Probiotics (still in trials, if have imbalance in gut, this rebalances bacteria by certain species)
4. New biologicals
  1. Fontolizumab- IFN-y block (proinflamm cytokine)-but req for anti-viral etc so side effects?
  2. Abatacept- CD28 block-req for T cell activation
  3. Visilizumab- CD3 block-T cell activator
  4. Natalizumab- a4b7 & a4b1 block-alot of immune cells have these integrants for adhesion and entry into inflammatory tissues: block this entry

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Gastrointestinal & endocrine pharmacology 2

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	Creado por tanitia.dooley hace alrededor de 11 años