Three drug types used to inhibit innate, humoral, and cell-mediated immunity.
slowing proliferation of activated B and T cells (S phase inhibitors)
corticosteroids (anti-inflammatory effects - cytokines)
cyclosporin A, FK 506, rapamycin - inhibit IL-2 transcription, bloccking T cell proliferation and activation
Neoral is oral cyclosporin A
Cyclosporin blocks T cell activation through inhibition of IL-2 and IFN-γ. Molecularly, cyclosporin complexes with cyclophilin, an inhibitor of calcinurin. Calcinurin normally dephosphorylates NF-AT, promoting transcription of cytokines as mentioned above.
Cyclosporin also alters fibroblast metabolism of collagen.
Acute nephrotoxicity can result from renal vasoconstriction.
Hyperkalemia, hypomagnesemia, hypertension, hepatotoxicity, gum hyperplasia, and hirsuitism can all follow cyclosporin.
Chronic nephrotoxicity can be caused by glomerular ischemia and interstitial fibrosis.
metabolized by CYP 3A4; drugs that induce cytochrome CYP3A4 lower drug level.
Azathioprine is metabolized to 6-mercaptopurine, inhibiting purine synthesis and thereby DNA synthesis. Cell proliferation is therefore attenuated, particularly in lymphocytes and neutrophils.
Allopurinol can cause toxic levels by inhibiting xanthine oxidase.
renal and hepatic excretion
Inhibits calcinurin, preventing transcription of IL-2 and thereby T cell activation.
Mycophenolate inhibits inosine monophosphate dehydrogenase, required for DNA synthesis. It inhibits T and B cell function.