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