Describe the effect that cyclosporine has had on transplantation success?
Improved 5-year survival rate since introduction in 1983.
Similarities and differences among cyclosporine, tacrollimus, and sirolimus?
Cyclosporine & Tacrolimus: (calcineuron inhibitors) - cyp3A4, nephrotoxicity, administered PO or IV, both can cause hyperglycemia (much higher in Tacrolimus). Cyclosporine forms complex with cyclophilin. Tacrolimus forms complex with FKBP - both inhibit calcineuron preventing IL-2.
Sirolimus: Binds to FKBP, but inhibits mTOR preventing T cell proliferation. Nephrotoxicity concern. CYP3A4. Used primarily in kidney transplants.
Why are anti-metabolites effective against proliferating lymphocytes?
Purine needed for DNA (A and G backbone)
Inhibits proliferation of fast-growing T & B
Why are certain antibodies useful for immunosuppression?
Antibodies bind to and inhibit important immunological cells/signalers: muromonab (CD3), Basiliximab (IL-2 receptor antagonist, CD25), Adalimumab (TNF-α).