Calcineurin Inhibitors

Calcineurin inhibitors (CNIs) prevent transplant rejection by blocking calcineurin, a phosphatase that activates the transcription factor NFAT in T-lymphocytes. Without NFAT activation, T-cells cannot produce interleukin-2 (IL-2), the cytokine that drives T-cell proliferation. No IL-2 means no immune attack on the transplanted organ. Tacrolimus is roughly 100 times more potent than cyclosporine at suppressing IL-2 production and is now the preferred agent for most solid organ transplants. Cyclosporine remains used in certain bone marrow transplants and autoimmune conditions like severe psoriasis and rheumatoid arthritis. Both drugs have narrow therapeutic windows requiring trough-level monitoring: cyclosporine trough targets vary by transplant type but generally 100–300 ng/mL early post-transplant, tacrolimus troughs typically 5–15 ng/mL. Nephrotoxicity is the most clinically significant adverse effect of both — rising creatinine and BUN require immediate evaluation. The nurse monitors serum creatinine, BUN, potassium, magnesium, glucose, and drug trough levels. Tacrolimus carries a higher risk for hyperglycemia and neurotoxicity (tremors, headache, seizures), while cyclosporine is more associated with gingival hyperplasia, hirsutism, and hypertension. Both cause hyperkalemia and hypomagnesemia. Both are metabolized via CYP3A4, so grapefruit juice is strictly avoided — it raises drug levels unpredictably. Infection risk is elevated; the client must report fever, sore throat, or any sign of infection immediately.