Deja Ch 10 Random Immunosuppressants

Question 1

What are the main targets of immunosuppressive agents?

Answer 1

Inhibition of gene expression; inhibition of lymphocyte signaling and activation; depletion of proliferating lymphocytes; inhibition of cytokine action; depletion of specific immune cells; blockade of costimulation; blockade of cell adhesion and migration; inhibition of complement activation

Question 2

Which agents are signaling inhibitors of B-/T-cell proliferation?

Answer 2

Cyclosporine A, tacrolimus, and sirolimus

Question 3

What is the mechanism of action of cyclosporine A?

Answer 3

Complexes with cyclophilin to inhibit calcineurin, thereby decreasing interleukin (IL)-2, which is the main inducer for activation of T lymphocytes

Question 4

What are the main therapeutic indications of cyclosporine A?

Answer 4

Prevention of organ rejection in heart, kidney, and liver transplants

Question 5

What are the adverse effects of cyclosporine A?

Answer 5

Nephrotoxicity; hepatotoxicity; cytomegalovirus (CMV) infections; hypertension; hyperkalemia; hirsutism; glucose intolerance; gingival hyperplasia; tremor; upper respiratory infections; anemia; leukopenia; thrombocytopenia

Question 6

Name three medications that can cause gingival hyperplasia:

Answer 6

1. Cyclosporine 2. Phenytoin 3. Nifedipine

Question 7

What major hepatic enzyme metabolizes cyclosporine A?

Answer 7

CYP 3A4

Question 8

Cyclosporine A becomes more effective as an immunosuppressant when combined with what class of drugs?

Answer 8

Glucocorticoids

Question 9

FK506 is also known as?

Answer 9

Tacrolimus

Question 10

What are the main therapeutic indications of tacrolimus?

Answer 10

Prevention of organ rejection in liver and kidney transplants

Question 11

What is the mechanism of action of tacrolimus?

Answer 11

It inhibits calcineurin by binding to FK binding protein (FKBP) rather than cyclophilin, cyclosporin’s target protein. It inhibits the signaling pathway coupling cell receptor activation of IL-2 gene transcription (IL-2 synthesis).

Question 12

What is the mechanism of action of sirolimus?

Answer 12

It blocks IL-2 receptor signaling required for cell activation and proliferation. It forms a complex with the immunophilin FKBP, it does not affect calcineurin activity, but inhibits the kinase mTOR, which is necessary for cell growth and proliferation.

Question 13

What are the adverse effects of tacrolimus?

Answer 13

Nephrotoxicity; neurotoxicity; hypertension; headache; tremor; rash; hyperglycemia; hyperkalemia; anemia; leukocytosis; thrombocytopenia

Question 14

Which murine monoclonal antibody interferes with T-lymphocyte function by binding to CD3 glycoprotein?

Answer 14

Muromonab-CD3 (OKT3)

Question 15

Which cytotoxic immunosuppressant is an alkylating agent?

Answer 15

Cyclophosphamide

Question 16

Which immunosuppressant is a derivative of 6-mercaptopurine, antagonizes purine metabolism, and is cytotoxic to lymphocytes?

Answer 16

Azathioprine

Question 17

Which immunosuppressant inhibits inosine monophosphate dehydrogenase, thereby inhibiting de novo guanosine nucleotide synthesis?

Answer 17

Mycophenolate mofetil