This is a brief presentation of CNIs the differences

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

3. 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)

4. 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

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

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

7. 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.

8. Pharmacokinetics
• Absorption
• Distribution
• Metabolism
• Excretion

9. Therapeutic Drug-Level Monitoring

11. 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.