Immunosuppressive Drugs

Question 1

CALCINEURIN INHIBITORS

Answer 1

Cyclosporine, Tacrolimus

Question 2

• binds to a cytoplasmic receptor protein called cyclophilin, resulting in the inhibition of calcineurin activity. This blocks the dephosphorylation events critical for cytokine gene expression and T cell activation

Answer 2

Cyclosporine

Question 3

• major adverse effect is renal toxicity which must be distinguished from graft rejection in kidney transplantation. Nephrotoxicity can occur in as many as 75% of patients

Answer 3

Cyclosporine

Question 4

• binds to a cytoplasmic receptor protein called FKBP (FK506 binding protein), resulting in the inhibition of calcineurin activity. This blocks the dephosphorylation events critical for cytokine gene expression and T cell activation.
• 100 times more potent than cyclosporine.

Answer 4

Tacrolimus

Question 5

ANTIPROLIFERATIVE/ANTIMETABOLIC DRUGS

Answer 5

Sirolimus, Mycophenolate Mofetil

Question 6

Binds to FKBP to inhibit a key enzyme in cell cycle progression (mammalian kinase target of rapamycin, mTOR). This blocks cell cycle progression from G1 to S phase.

Answer 6

Sirolimus

Question 7

Dose dependent increase in cholesterol and triglycerides. Nephrotoxicity in combination with cyclosporine. Increased risk of lymphomas and infections. A substrate for cytochrome CYP3A4 with the potential for drug interactions.

Answer 7

Sirolimus

Question 8

A metabolite is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), an important enzyme in the de novo pathway of guanine nucleotide synthesis. B and T cells are highly dependent on this pathway for cell proliferation, while other cell types can use salvage pathways.

Answer 8

Mycophenolate Mofetil

Question 9

ANTIBODIES

Answer 9

Anti-thymocyte globulin, Muromonab-CD3, Daclizumab or Basiliximab

Question 10

• The immunoglobulin binds to the thymocytes in the circulation, resulting in lymphopenia and impaired T cell immune responses.

Answer 10

Anti-thymocyte globulin (ATG)

Question 11

• Toxicity is primarily due to the immunoglobulin being recognized as foreign resulting in serum sickness and nephritis

Answer 11

Anti-thymocyte globulin (ATG)

Question 12

• A mouse monoclonal antibody that binds to the  chain of CD3 glycoprotein that is part of the T cell receptor complex on T lymphocytes. When this happens, the T cell receptor complex is internalized preventing further antigen recognition.

Answer 12

Muromonab-CD3

Question 13

Binds to the IL-2 receptor present on activated, but not resting, T cells and block IL-2 mediated T cell activation events.

Answer 13

Daclizumab or Basiliximab

Question 14

SITE OF ACTION: Glucocorticoids

Answer 14

Glucocorticoid response elements in DNA

regulate gene transcription

Question 15

SITE OF ACTION: Muromonab-CD3

Answer 15

T-cell receptor complex (blocks antigen recognition)

Question 16

SITE OF ACTION: Both Cyclosporine and Tacrolimus

Answer 16

Calcineurin (inhibits phosphatase activity)

Question 17

SITE OF ACTION: Mycophenolate mofetil

Answer 17

Inosine monophosphate dehydrogenase (inhibits activity)

Question 18

SITE OF ACTION: Daclizumab, Basiliximab

Answer 18

IL-2 receptor (block IL-2-mediated T-cell activation)

Question 19

SITE OF ACTION: Sirolimus

Answer 19

Protein kinase involved in cell-cycle progression

mTOR) (inhibits activity