calcineurin Inhibitors

This is a brief presentation of CNIs the differences

1. In the name of God CNIs In the name of God Dr. N.Esfandiar Mofid children’s hospital Shahid beheshti medical university

2. Describes the effect a drug has on the body. This includes the agent‘s therapeutic activity (its mechanism of action) and any untoward effects it may cause (its adverse effect profile)

3. Calcineurin Inhibitors: Mechanism of Action CsA: Cyclosporine FK506: Tacrolimus FKBP: FK Binding Protein CpN: Cyclophilin NF-AT: Nuclear Factor of Activated T-cells (c- cytosolic component; n- nuclear component). Stepkowski, Expert Rev Mol Med , 2000;2(4):1

4. Mechanism of antiproteinuric effect of CNIs Role of podocytes in preteinuria

5. Nature Medicine 14 , 931 - 938 (2008)

6. Calcineurin Inhibitors Two agents in clinical practice: Cyclosporine (Sandimmune ® , Gengraf ® , Neoral ® , generic; CysA) Tacrolimus (Prograf ® , supratac,generic; FK506). Generics NOT clinically therapeutically equivalent. At present are key to maintenance immunosuppression and a component of the majority of transplant protocols.

7. Pharmacokinetics Absorption Distribution Metabolism Excretion

8. Therapeutic Drug-Level Monitoring

9. Calcineurin Inhibitors: Adverse Effects Nephrotoxicity: Functional decrease in blood flow from afferent arteriolar vasoconstriction. Thrombotic microangiopathy (rare). Chronic interstitial fibrosis. Hyperkalemia, hypomagnesemia and type IV renal tubular acidosis. Cyclosporine thought to be more nephrotoxic.

10. Thank you