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Therapeutics Spring 2015 > Immunosuppressive drugs > Flashcards

Immunosuppressive drugs Flashcards

1
Q

What are two general types of immunosuppressive agents?

A
  1. anti-rejection induction agents

2. maintenance immunotherapy agents

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2
Q

What are anti-rejection induction agents?

A

short term prophylaxis against early acute rejection

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3
Q

What are maintenance immunotherapy agents?

A

to prevent future rejection reactions from occuring

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4
Q

What are three kinds of induction agents?

A
  1. antibody mediated therapies
  2. cell depleting antibodies
  3. antagonistic antibodies (non cell depleting)
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5
Q

What are two kinds of antibody based therapy?

A

Type 1 and type 2

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6
Q

What are type 1 antibody based induction therapy?

A

Igs that bind surface markers on immune cells

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7
Q

What are type 1 antibody based induction therapy?

A
  • Igs that bind surface markers on immune cells

- Deplete immune cells by apoptosis, ADCC, NK cells or CDC

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8
Q

What are type 2 antibody based induction therapy?

A 
Not as effective as class 1, but less toxic
Antibodies that are antagonists of the ligands needed for lymphocytes to proliferate and be activated.
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9
Q

What are three drugs that belong to the antibody based induction therapy class?

A

polyclonal antisera
chimerica monoclonals
humanized monoclonals

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10
Q

What are three drugs that belong to the antibody based induction therapy class?

A

polyclonal antisera
chimerica monoclonals
humanized monoclonals

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11
Q

What are type 2 antibody based induction therapy?

A 
Not as effective as class 1, but less toxic
Antibodies that are antagonists of the ligands needed for lymphocytes to proliferate and be activated.
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12
Q

What kind of agent is polyclonal anti-thymocyte globulins,?

A

cell depleting induction agent

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13
Q

What are some side effects of cell depleting antibodies?

A 
cytokine storm (t cells send out inflammatory mediatiors)
reactivation of herpes viral diseases (CMV, EBV, varicella), dose dependent serum sickness
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14
Q

What kind of agent is alemtuzumab?

A

humanized monoclonal antibody against CD52 expressed on lymphocytes but not hematopoietic precursors
- technically an anti tumor agent, not FDA approved as an induction agent

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15
Q

What do cell depleting antibodies do?

A

They kill T cells through ADCC, CDCC and CDC by binding CD3/CD4/CD28 integrins

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16
Q

What are some side effects of cell depleting antibodies?

A 
cytokine storm (t cells send out inflammatory mediatiors)
reactivation of herpes viral diseases (CMV, EBV, varicella)
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17
Q

What is the mechanism behind antagonistic antibodies?

A

Antibodies against CD25, act as antagonists to IL-2 receptor on activated T cells

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18
Q

What are ADEs of alemtuzumab?

A

neutropenia
thrombocytopenia
anemia

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19
Q

What kind of antibody is basilixumab (Simulect)?

A 
Chimeric monoclonal ab.
antagonistic antibody (non depleting)
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20
Q

What is the mechanism behind antagonistic antibodies?

A

Antibodies against CD25, act as antagonists to IL-2 receptor on activated T cells

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21
Q

What are some ADEs for corticosteroids?

A 
increased risk of infection
decreased wound healing
adrenal insufficiency
decreased bone density
skin fragility
cardiovascular complications
cushings like syndrome
insomnia
psychiatric- irritability and activity
22
Q

What kind of immunosuppressive agent are glucocorticoids?

A

Maintenance agent

23
Q

How do glucocorticoids (prednisone) suppress the immune system?

A

Inhibit the expression of cytokines, enzymes, receptors and adhesion molecules.

24
Q

What is the mechanism of cyclosporine?

A

Cyclosporine binds cyclophylin and together the complex blocks the function of calcineurin (to dephosphorylate NFAT, no NFAT = no IL-2 so no T Cell proliferation)

25
Q

What are two calcineurin inhibitors?

A

cyclosporine

tacrolimus

26
Q

what kind of molecule is cyclosporine?

A

nonribosomal cyclic peptide

27
Q

What is the mechanism of cyclosporine?

A

Cyclosporine binds cyclophylin and together the complex blocks the function of calcineurin (to dephosphorylate NFAT, no NFAT = no IL-2 so no T Cell proliferation)

28
Q

What kind of molecule is tacrolimus?

A

macrolide antibiotic

29
Q

What kinds of transplants is tacrolimus approved for?

A

kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, bone marrow and limb.

30
Q

What is the mechanism of tacrolimus?

A

It binds to immunophillin FKBP-12 to inhibit calcineurin

31
Q

What are the side effects of tacrolimus?

A

infection, HTN, abnormal renal function, acne, hair growth, diabetes

32
Q

What kind of drug is Sirolimus (rapamycin)?

A

antiproliforative, antimetabolic

33
Q

What kind of molecule is Sirolimus?

A

Macrolide antibiotic

34
Q

What kind of molecule is Everolimus?

A

antiproliferative, antimetabolic

methyl derivative of sirolimus

35
Q

What class of drugs does Mycophenolate Mofetil (Cell Cept) belong too?

A

Antiproliferative, antimetabolite

36
Q

Is Sirolimus nephrotoxic?

A

No

37
Q

Can you use Sirolimus in lung and heart transplants?

A

NO

38
Q

Why is mycophenolate mofetil an effective antiproliferative?

A

It blocks the de novo synthesis of nucleotides, lymphocytes are very dependent on this type of synthesis to proliferate

39
Q

What is the mechanism behind mycophenolate mofetil?

A

It is a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH)

40
Q

Which type of IMPDH is mycophenolate mofetil specific for?

A

type 2 in lymphocytes

41
Q

Why is mycophenolate mofetil an effective antiproliferative?

A

It blocks the de novo synthesis of nucleotides, lymphocytes are very dependent on this type of synthesis to proliferate

42
Q

What kind of drug is azathioprine (Imuran)?

A

antiproliferative
more toxic
less specific for lymphocytes

43
Q

how does methotrexate work?

A

Dihydrofolate reductase inhibitor that blocks thymidine biosynthesis
antitumor agent

44
Q

What is an example of an off label immunosupressant?

A

Cytotoxic and antimetabolic agents used in cancer

45
Q

What kind of drug is Balatacept (Nulojix)?

A

A fusion protein of Fc fragments of human IgG1 linked to the extracellular domain of CTLA-4
- blocks the t cell costimulatory signal from B7 and CD28

46
Q

how does methotrexate work?

A

Dihydrofolate reductase inhibitor that blocks thymidine

47
Q

How does leflunomide work?

A

Dihydrooratate dehydrogenase inhibitor blocks denovo synthesis of UMP

48
Q

What kind of drug is Balatacept (Nulojix)?

A

A fusion protein of Fc fragments of human IgG1 linked to the extracellular domain of CTLA-4
- blocks the t cell costimulatory signal from B7 and CD28

49
Q

What is rituximab?

A

Rituxan

chimeric monoclonal Ab against APC CD20 (B Cells)

50
Q

What is eculizumab?

A

humanized antibody against C5 component of compliment

C5a is an anaphlotoxin, C5b makes the MAC complex

Therapeutics Spring 2015 (12 decks)

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