Immunosuppressants

Question 1

Cyclosporine:

1) MOA
2) Use
3) Toxicity

Answer 1

1) Prevents IL-2 transcription by inhibiting calcineurin, via binding cyclophilin–> suppresses T-cell activation
2) Transplant rejection prophylaxis, psoriasis, RA
3) NEPHROTOXIC. Also, HTN, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism

Question 2

Tacrolimus (FK506):

1) MOA
2) Use
3) Toxicity

Answer 2

1) Prevents IL-2 transcription by inhibiting calcineurin, via binding FKBP–> suppresses T-cell activation
2) Transplant rejection prophylaxis
3) NEPHROTOXIC. Also, HTN, hyperlipidemia, neurotoxicity, DM

Question 3

Sirolimus (Rapamycin):

1) MOA
2) Use
3) Toxicity

Answer 3

1) Blocks IL-2R signaling by inhibiting mTOR, via binding at FKBP–> suppresses T-cells and B-cells
2) KIDNEY transplant rejection prophylaxis. Synergistic with cyclosporine.
3) Pancytopenia, insulin resistance, hyperlipidemia

“Kidney sir-vives!”

Question 4

Daclizumab:

1) MOA
2) Use
3) Toxicity

Answer 4

1) Monoclonal antibody; antagonist at IL-2R
2) Kidney transplant rejection prophylaxis
3) Edema, HTN, tremor

Question 5

Basiliximab:

1) MOA
2) Use
3) Toxicity

Answer 5

1) Monoclonal antibody; antagonist at IL-2R
2) Kidney transplant rejection prophylaxis
3) Edema, HTN, tremor

Question 6

Azathioprine:

1) MOA
2) Use
3) Toxicity

Answer 6

1) Inactive analogue for 6-MP; inhibit nucleotide/DNA synthesis
2) Transplant rejection prophylaxis, other autoimmune conditions (esp. RA, Crohn’s disease, glomerulonephritis)
3) Leukopenia, anemia, thrombocytopenia

Question 7

Mycophenolate mofetil

1) MOA
2) Use
3) Toxicity

Answer 7

1) Inhibits IMP hydrogenase, preventing purine/DNA synthesis
2) Transplant rejection prophylaxis, SLE
3) GI upset, panyctopenia, HTN, hyper-GLU. Invasive CMV infx

Question 8

Corticosteroids:

1) MOA
2) Use
3) Toxicity

Answer 8

1) inhibits NF-κB TF, supressing cytokine production; induces T cell apoptosis
2) Transplant rejection prophylaxis; many autoimmune and inflammatory disorders
3) Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, avascular necrosis @ femoral head; Cushing syndrome