Immunosuppressant Therapy

Question 1

Induction therapy

Answer 1

Given at time of transplant. Very Potent, prolonged use is toxic. May include donor specific transfusion or irradiation as drug alternatives.

Question 2

Maintenance Therapy

Answer 2

Lower potency, tolerable in chronic doses

Question 3

Rescue Therapy

Answer 3

Intense, applied inresponse to rejection episode. Chronically intolerable

Question 4

Describe typical Maintenance Therapy

Answer 4

Involves three drugs that work at different levels of the inflammatory cascade:
Calcineurin Inhibitor, anti-proliferative, steroid

Question 5

What does anti-cd3 therapy accomplish?

Answer 5

Blocks T-Cell activation

Question 6

What does Calcineurin usually do?

Answer 6

Controls nuclear access of NFAT (Nuclear factor of activated transcription)

Question 7

What do you gain by inhibiting Calcineurin?

Answer 7

NFAT can’t access the nucleus and mediate IL-2 transcription

Question 8

What cell surface receptor does IL-2 normally interact with?

Answer 8

CD-25

Question 9

Guess what you can use to keep adjacent T-cells from becoming activated by IL-2

Answer 9

Monoclonal abs for CD-25

Question 10

What does inhibition of mTOR accomplish

Answer 10

Prevents IL-2 from having an effect on cells. It can bind but nothing happens

Question 11

What do drugs that block cell cycle accomplish

Answer 11

Prevent proliferation of T cells.

Question 12

Anti-CD52 drugs?

Answer 12

CD-52 expressed on surfact of mature lymphocytes. Binding of a mab to these identifies the cell for lysis.

Question 13

How do you target an individual T Cell for lysis

Answer 13

Polyclonal IgG against human T-cells derived from horses (Atgam) or rabbitts (thymoglobulin). Targets cells for complement opsonization and lysis.

Question 14

What are the major risks associated with immunosuppressants?

Answer 14

1. ) Patients are immuno depressed and should receive prophylactic therapy against opportunistic infections
2. ) Secondary malignancy or Lymphoproliferative disorder
3. ) Cytokine release syndrome

Question 15

What are the major calcineurin inhibitors?

Answer 15

Cyclosporin and tacrolimus (tacrolimus is much more powerful).

Question 16

What is the major tocxicity associated with calcineurin inhibitors?

Answer 16

Renal (which blows because they are used with kidney transplants. It is often difficult to tell transplant rejection apart from CNI toxicity.

Question 17

Some other CNI toxicities:

Answer 17

Cardiovascular, Neurological, gengival hyperplasia, hypertrychosis (no idea what that is, secondary malignancy

Question 18

How do corticosteroids work?

Answer 18

Bind to GR and GR can inhibit inflammatory gene transrption directly by binding to HAT or can recruit HDAC2 and cause it to deacetylate genes leading to suppression of active inflammatory genes

Question 19

Toxicities of corticosteroids?

Answer 19

Neutrophilia, eosinopenia, monocytopenia, poor healing (protein metabolism), cushings syndrome, depression etc…

Question 20

Name an mTor inhibitor

Answer 20

Sirolimus

Question 21

What does Sirolimus do?

Answer 21

Inhibits 2nd phase of T cell activation. Prevents B cell differentiation into plasma cells.

Question 22

What are the major toxicities of Sirolimes

Answer 22

Fatal hepatic necrosis, Can affect cells outside the immune system as well

Question 23

Name the Cell Cycle disruptors

Answer 23

Mycofenolate Mofetil, Axathioprine, Cyclophoshamide, Methotrexate.

Question 24

Most common sideeffects of mycofenolate mofetil?

Answer 24

GI stuff

Question 25

Most common sideeffects of Azathioprine?

Answer 25

Birth defect risk

Question 26

Cyclophosphamide

Answer 26

Pro drug

Question 27

Methotrexate does what?

Answer 27

Inhibits S phase of cell cycle

Question 28

What tissues are most sensitive to Methotrexate?

Answer 28

Those that are dividing at a high rate