SOT 2005 Review Notes

Corticosteroids
 First line treatment for acute allograft rejection
o Prednisone and prednisolone (Prednisone 80% bioavailability of prednisolone)
o Methylprednisolone – IV inpatient treatment
o Glucocorticoid > mineralocoritcoid
o 20 mg/day initial and 5 mg/day maintenance
 MOA:
o Stabilization of lysosomal membranes
o Suppression of prostaglandin synthesis
o Reduction of histamine and bradykinin release
o Lowering capillary permeability
o Cross into cytoplasm  bind to glucocoticoid receptors anchored by heat shock proteins
 relase heat shock proteins allowing receptor complex to translocated to the cell
nucleus  gene transcription alternation (nuclear activating facotr family)
 Net result decreased inflammation by decreaseing IL-1, IL-2, IFN-gamma, TNF-
alpha
 Decrease number CD4 cells
 Diabetes (altered carb metabolosis), fat redistribution, and muscle weakness (protein loss)
 Steroid withdrawal liver:
o Little increased risk of rejection with reduced hypertension, lower serum cholesterol ,
less obesity and less diabetes
o After free from rejection at 3 months, can do early steroid withdrawl and be safe
Azathioprine
 MOA:
o Metabolized to 6MP  incorporated into replciated DNA and halt replication
o Block de novo pathway of purine synthesis by formation of thio-inosinic acid 
specifictiy of action on lymphocytes which lack slavage pathways for purine synthesis
o Inteferes with CD28 receptor signaling
 Blocks Rac1  converts CD28 into apoptoic signal  deleting activated T
lymphocytes