Agents that block lymphocyte activation and proliferation. Reduce acute transplant rejection by suppressing cellular immunity (used as prophylaxis). Frequently combined to achieve greater efficacy with ¯ toxicity. Chronic suppression risk of infection and malignancy.
|Cyclosporine||Calcineurin inhibitor; binds cyclophilin. Blocks T-cell activation by preventing IL-2 transcription.||Psoriasis, rheumatoid arthritis.||Nephrotoxicity (arteriolar hyalinization, tubular vacuolization), hypertension, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism.||Both calcineurin inhibitors are highly nephrotoxic|
|Tacrolimus (FK506)||Calcineurin inhibitor; binds FK506 binding protein (FKBP). Blocks T-cell activation by preventing IL-2 transcription.||Similar to cyclosporine, risk of diabetes and neurotoxicity; no gingival hyperplasia or hirsutism.||Both calcineurin inhibitors are highly nephrotoxic|
|Sirolimus (Rapamycin)||mTOR inhibitor; binds FKBP. Blocks T-cell activation and B-cell differentiation by preventing response to IL-2.||Kidney transplant rejection prophylaxis specifically.||“PanSirtopenia” (pancytopenia), insulin resistance, hyperlipidemia; not nephrotoxic.||Kidney “sir-vives.” Synergistic with cyclosporine. Also used in drug-eluting stents.|
|Basiliximab||Monoclonal antibody; blocks IL-2R.||Kidney transplant rejection prophylaxis specifically.||Edema, hypertension, tremor.|
|Azathioprine||Antimetabolite precursor of 6-mercaptopurine. Inhibits lymphocyte proliferation by blocking nucleotide synthesis.||Rheumatoid arthritis, Crohn disease, glomerulonephritis, other autoimmune conditions.||Pancytopenia.||6-MP degraded by xanthine oxidase to oxidized metabolites, toxicity by allopurinol. 6-MP is also degrated by thiopurine methyltransferase to 6-methylmercaptopurine; Pronounce “azathiopurine.”|
|Mycophenolate Mofetil||Reversibly inhibits IMP dehydrogenase, preventing purine synthesis of B and T cells.||Lupus nephritis.||GI upset, pancytopenia, hypertension, hyperglycemia. Less nephrotoxic and neurotoxic.||Associated with invasive CMV infection.|
|Glucocorticoids||Inhibit NF-κB. Suppress both B- and T-cell function by ¯ transcription of many cytokines. Induce T cell apoptosis.||Many autoimmune and inflammatory disorders, adrenal insufficiency, asthma, CLL, non-Hodgkin lymphoma.||Cushing syndrome, osteoporosis, hyperglycemia, diabetes, amenorrhea, adrenocortical atrophy, peptic ulcers, psychosis, cataracts, avascular necrosis (femoral head).||Demargination of WBCs causes artificial leukocytosis. Adrenal insufficiency may develop if drug is stopped abruptly after chronic use.|