Drugs used for Immunomodulation

Question 1

What are the four general principles of immunosuppression?

Answer 1

1. The primary response is more efficiently suppressed compared to the secondary response
2. Different drugs act better on different parts of immunosupression
3. It is better to give the drug before the antigen is presented
4. Drugs are used synergestically

Question 2

Which two drugs are calcineurin inibitors and explain their action

Answer 2

1. Cyclosporin A and Tacrolimus
2. They inhibit the calineurin’s actions on p-NFAT, thus there is not accumulation of IL-2 and at higher doses IL-2 receptor formation and antigen presentation is inhibited
3. Cyclosporin binds with cyclophillin and Tacrolimus binds wit FKBP

Question 3

What are the three side effects of CSA

Answer 3

1. Renal toxicity
2. Hypertension
3. CNS toxicity

Question 4

What enzyme system metabolizes CSA and is important because other drugs might stimulate its activity or decrease it, which then affects the CSA concentration in the blood?

Answer 4

CYP3A system

Question 5

This drug binds to FKBP, but acts on mTOR, a kinase that acts to increase the protein synthesis and is required for efficient T cell activation

Answer 5

Rapamycin (use separately with CSA because they enhance each others’ toxic effects

Question 6

This cytotoxic drug is used to treat cancer and RA, inhibits dihydrofolate reductase which is needed for the synthesis of TMP and purines, is very hepatotoxic

Answer 6

Methotrexate

Question 7

This cytotoxic drug inhibits IMP dehydrogenase which is needed for de novo purine synthesis. It is approved for use after a renal transplant. It stops lymphocyte proliferation and antibody formation

Answer 7

Mycophenolate

Question 8

This cytotoxic drug inhibits dihydroorate dehydrogenase which is needed for de novo pyrimidine synthesis. It is approved for use for RA, but is can severe to life threatening heptotoxicity.

Answer 8

Leflunomide

Question 9

This cytotoxic drug blocks purine synthesis and is converted to mercaptopurine

Answer 9

Azathioprine

Question 10

A glucocorticoid that can be used in conjunction with azathipoprine and cyclosporin A to prevent rejection, also used extensively to treat rheumatoid arthritis

Answer 10

prednisone

Question 11

An anti-TNF alpha agent the binds to TNF-alpha with high affinity, approved for treating symptoms of RA, and is used in conjunction with methotrexate when methotreaxte does not work alone

Answer 11

infliximab

Question 12

An anti-TNF alpha agent that contains the ligand binding portion of a human TNF-alpha receptor fused to the Fc portion of IgG1

Answer 12

Ethanercept

Question 13

What are the overall effects of immunosuppresive therapy

Answer 13

1. Increased risk of infection
2. Increased risks of malignant neoplasms because of a loss of immunesurveillance and rapid proliferation of stem cells that are restoring the immune system

Question 14

A recombinant GM-CSF used to reduce the time of neutropenia in cancer patients, at large doses monocytosis and eosionphilia are observed

Answer 14

Sargramostim

Question 15

These drugs are recombinant G-CSF and increase neutrophil production and enhances cytotoxic and phagocytic function

Answer 15

Filgramstim, Pegfilgrastim (has a higher half life than filgrastim)