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Pharm > Immunosuppressants > Flashcards

Immunosuppressants Flashcards

1
Q

What are the three general uses of immunosuppressants?

A

transplantations
Autoimmune diseases
Inflammatory diseases

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2
Q

What are grafts between identical twins called?

A

Isografts

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3
Q

What are allografts?

A

Grafts from other people

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4
Q

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

A

False

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5
Q

What are the four major classes of Immunosuppressants?

A
  • Glucocorticoids
  • Calcineurin inhibitors
  • Anti-proliferative/antimetabolic agents
  • biologicals
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6
Q

Malignancies with immunosuppressants usually have what etiology?

A

Latent viral infections

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7
Q

What are steroids, technically?

A

Compounds with a common ring structure

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8
Q

What are corticosteroids, technically?

A

Adrenal cortex steroids

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9
Q

What are the two major MOAs of glucocorticoids?

A

Genomic

Non-genomic

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10
Q

What are the genomic effects of glucocorticoids?

A

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

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11
Q

What are the non-genomic effects of glucocorticoids?

A

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

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12
Q

What are the effects of glucocorticoids?

A
  • Rapid decrease in peripheral blood lymphocyte

- Downregulate IL-1, IL-6, IFN-g, TNF-a

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13
Q

What is the function of IL-2?

A

T cell proliferation

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14
Q

What is the effect of glucocorticoids on PMNs?

A

reduce chemotaxis and lysosomal enzyme release

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15
Q

What is the effect of glucocorticoids on humoral immunity?

A

Little

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16
Q

What is the effect of CD3?

A

***Cytokine storm

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17
Q

What are the adverse effects of glucocorticoids?

A

Growth retardation
Impaired wound healing
HTN
Hyperglycemia

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18
Q

Rapid withdrawal of glucocorticoids may result in what?

A

Glucocorticoid crisis

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19
Q

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

A

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

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20
Q

What is the half-life of prednisone?

A

5 hours (intermediate)

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21
Q

What are the two, short acting glucocorticoids?

A

Cortisone

Hydrocortisone

22
Q

What are the four intermediate acting glucocorticoids?

A

Prednisone
Prednisolone
Methylprednisolone
Triamcinolone

23
Q

What are the two long acting glucocorticoids?

A

Dexamethasone

Betamethasone

24
Q

What is pulse therapy with glucocorticoid use?

A

Greater than 250 mg of prednisone for 1 day

25
Q

What is the MOA of cyclosporine?

A

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

26
Q

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

A

NFAT–leads to IL-2 production

27
Q

What is the function of IL-12?

A

Th1 cell production

28
Q

What is the function of IL-4?

A

Th2 cell production

29
Q

What are the therapeutic uses for cyclosporine? Side effects?

A

Prophylaxis for kidney transplant, RA

Nephrotoxic, HTN, Hirsutism

30
Q

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

A

Inhibits p450 enzyme, causing an increase in cyclosporine and tacrolimus

31
Q

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

A

calcineurin inhibitor, preventing NFAT phosphorylation

Prophylaxis of allograft rejection

Nephro/neurotoxic, HTN,
DM,

32
Q

What is the MOA of Azathioprine?

A

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

33
Q

What are the two purines?

A

A

G

34
Q

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

A

Lymphocytes do not have a salvage pathway

35
Q

What are the therapeutic uses of Azathioprine? Adverse effects?

A

Organ transplant rejection
RA

Myelosuppression
Hepatotoxic

36
Q

Azathioprine increases that susceptibility to what viral infections?

A

Varicella

HSVs

37
Q

What is the MOA of Mycophenolate Mofetil?

A

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
Q

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

A

Transplant rejection
SLE

CMV infections
Teratogenic
Leukopenia

39
Q

What is the MOA of sirolimus?

A

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

40
Q

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

A

Renal transplant

Anemia
Hypokalemia

41
Q

What is Antithymocyte globulin?

A

rabbit serum antibodies against human thymocytes

42
Q

What is the CD protein that all T cells express?

A

CD3

43
Q

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

A

Complement mediated cytotoxicity

Inhibition of lymphocyte functions by binding surface molecules

44
Q

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

A

Induction immunosuppression

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

45
Q

What is the MOA of Muromonab-CD3?

A

Mouse antibodies against CD3 cause T lymphocyte depletion

46
Q

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

A

Reverse organ transplant rxn

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

47
Q

What are the three Anti-TNF-alpha reagents?

A

Infliximab
Adalimumab
Etanercept

48
Q

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

A

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

49
Q

What is infliximab?

A

Anti-TNF alpha antibody

50
Q

What is Adalimumab?

A

Recombinant human IgG1 monoclonal against TNF-a

51
Q

What is Etanercept?

A

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

52
Q

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

A

Crohn’s, UC

Increase risk of infx and malignancies

Pharm (73 decks)

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