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calcineurin Inhibitors


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This is a brief presentation of CNIs the differences

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calcineurin Inhibitors

  1. 1. CNIs In the name of God Dr. N.Esfandiar Mofid children’s hospital Shahid beheshti medical university
  2. 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. 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. 4. Mechanism of antiproteinuric effect of CNIs Role of podocytes in preteinuria
  5. 5. Nature Medicine 14, 931 - 938 (2008)
  6. 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. 7. Pharmacokinetics • Absorption • Distribution • Metabolism • Excretion
  8. 8. Therapeutic Drug-Level Monitoring
  9. 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.