Which immunosuppressant drug acts as a calcineurin inhibitor and is commonly used in post-transplant rejection prophylaxis?

Explanation

## Calcineurin Inhibitors in Immunosuppression **Key Point:** Tacrolimus is a macrolide antibiotic that binds to FK-binding protein (FKBP12) and inhibits calcineurin, preventing T-cell activation and IL-2 production. **High-Yield:** Calcineurin inhibitors (tacrolimus and cyclosporine) are the cornerstone of post-transplant immunosuppression regimens because they: - Prevent dephosphorylation of NFAT (nuclear factor of activated T cells) - Block IL-2 and other cytokine production - Are highly effective in preventing acute rejection **Clinical Pearl:** Tacrolimus has a narrower therapeutic window than cyclosporine and requires therapeutic drug monitoring (target levels: 5–20 ng/mL depending on post-transplant phase). **Mnemonic:** **FKBP** = FK-binding protein; tacrolimus = FK506 (binds FKBP, hence the name). ### Mechanism Tacrolimus → binds FKBP12 → inhibits calcineurin → blocks NFAT dephosphorylation → ↓ IL-2, IFN-γ, TNF-α → ↓ T-cell proliferation. ### Common Adverse Effects - Nephrotoxicity (dose-limiting) - Neurotoxicity (tremor, headache, seizures) - Hyperglycemia - Hypertension - Hyperkalemia [cite:KD Tripathi 8e Ch 75]