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Flashcards in Immunosuppressants Deck (52):
1

What are the three general uses of immunosuppressants?

transplantations
Autoimmune diseases
Inflammatory diseases

2

What are grafts between identical twins called?

Isografts

3

What are allografts?

Grafts from other people

4

True or false: you can never truly induce remission of autoimmune diseases with immunosuppressants?

False

5

What are the four major classes of Immunosuppressants?

-Glucocorticoids
-Calcineurin inhibitors
-Anti-proliferative/antimetabolic agents
-biologicals

6

Malignancies with immunosuppressants usually have what etiology?

Latent viral infections

7

What are steroids, technically?

Compounds with a common ring structure

8

What are corticosteroids, technically?

Adrenal cortex steroids

9

What are the two major MOAs of glucocorticoids?

Genomic
Non-genomic

10

What are the genomic effects of glucocorticoids?

Binds to a cytosolic receptor, and translocates to the DNA (1% of genome) to alter transcription/translation

11

What are the non-genomic effects of glucocorticoids?

Can influence cell signalling pathways and intercalate into the cell membrane to alter ion transport

12

What are the effects of glucocorticoids?

-Rapid decrease in peripheral blood lymphocyte
-Downregulate IL-1, IL-6, IFN-g, TNF-a

13

What is the function of IL-2?

T cell proliferation

14

What is the effect of glucocorticoids on PMNs?

reduce chemotaxis and lysosomal enzyme release

15

What is the effect of glucocorticoids on humoral immunity?

Little

16

What is the effect of CD3?

***Cytokine storm

17

What are the adverse effects of glucocorticoids?

Growth retardation
Impaired wound healing
HTN
Hyperglycemia

18

Rapid withdrawal of glucocorticoids may result in what?

Glucocorticoid crisis

19

What is low, medium, high, and very high doses of glucocorticoids?

Low = (0, 7.5] mg
Med = (7.5, 30]
High = (30, 100]
Very high = (100, 250]

20

What is the half-life of prednisone?

5 hours (intermediate)

21

What are the two, short acting glucocorticoids?

Cortisone
Hydrocortisone

22

What are the four intermediate acting glucocorticoids?

Prednisone
Prednisolone
Methylprednisolone
Triamcinolone

23

What are the two long acting glucocorticoids?

Dexamethasone
Betamethasone

24

What is pulse therapy with glucocorticoid use?

Greater than 250 mg of prednisone for 1 day

25

What is the MOA of cyclosporine?

Suppress T cell-mediated immunity by forming a complex with cyclophilin, and prevent dephosphorylation of NFAT

26

What is the transcription factor that cyclosporine suppresses? What does this produce?

NFAT--leads to IL-2 production

27

What is the function of IL-12?

Th1 cell production

28

What is the function of IL-4?

Th2 cell production

29

What are the therapeutic uses for cyclosporine? Side effects?

Prophylaxis for kidney transplant, RA

Nephrotoxic, HTN, Hirsutism

30

What is the effect of grapefruit juice on cyclosporine? Tacrolimus?

Inhibits p450 enzyme, causing an increase in cyclosporine and tacrolimus

31

What is the MOA of tacrolimus? What are the therapeutic uses? Side effects?

calcineurin inhibitor, preventing NFAT phosphorylation

Prophylaxis of allograft rejection

Nephro/neurotoxic, HTN,
DM,

32

What is the MOA of Azathioprine?

Purine antimetabolite that is metabolized to 6-mercaptopurine to inhibit lymphocyte proliferation

33

What are the two purines?

A
G

34

Why is it that most cells can overcome Azathioprine actions, but lymphocytes cannot?

Lymphocytes do not have a salvage pathway

35

What are the therapeutic uses of Azathioprine? Adverse effects?

Organ transplant rejection
RA

Myelosuppression
Hepatotoxic

36

Azathioprine increases that susceptibility to what viral infections?

Varicella
HSVs

37

What is the MOA of Mycophenolate Mofetil?

Prodrug that is hydrolyzed to MPA, which inhibits inosine monophosphate dehydrogenase, which is required for the synthesis of guanine.

Inhibits T and B cells

38

What are the therapeutic uses, and side effects of mycophenolate?

Transplant rejection
SLE

CMV infections
Teratogenic
Leukopenia

39

What is the MOA of sirolimus?

Inhibits T lymph proliferation by binding to FKBP (same as tacrolimus), to inhibit mTOR, and cell cycle progression

40

What are the therapeutic uses, and side effects of sirolimus?

Renal transplant

Anemia
Hypokalemia

41

What is Antithymocyte globulin?

rabbit serum antibodies against human thymocytes

42

What is the CD protein that all T cells express?

CD3

43

What are the two mechanisms that Antithymocyte globulin uses to destroy thymocytes?

Complement mediated cytotoxicity

Inhibition of lymphocyte functions by binding surface molecules

44

What are the therapeutic uses, and side effects of Antithymocyte globulin?

Induction immunosuppression

TNF-a release (ILI)
Serum sickness
Anaphylaxis
*Cytokine storm*

45

What is the MOA of Muromonab-CD3?

Mouse antibodies against CD3 cause T lymphocyte depletion

46

What are the therapeutic uses, and side effects of Muromonab-CD3?

Reverse organ transplant rxn

Cytokine storm
Anaphylaxis
Will not work more than once (immune response)

47

What are the three Anti-TNF-alpha reagents?

Infliximab
Adalimumab
Etanercept

48

What is the MOA of Anti-TNF-alpha reagents?

Prevents TNF-alpha from binding to its receptors by binding directly to the cytokine

49

What is infliximab?

Anti-TNF alpha antibody

50

What is Adalimumab?

Recombinant human IgG1 monoclonal against TNF-a

51

What is Etanercept?

Ligand binding portion of human anti-TNF alpha fused to the Fc portion of human IgG1

52

What are the therapeutic uses, and side effects of Anti-TNF alpha reagents?

Crohn's, UC

Increase risk of infx and malignancies