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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
What are two calcineurin inhibitors?
cyclosporine | tacrolimus
26
what kind of molecule is cyclosporine?
nonribosomal cyclic peptide
27
What is the mechanism of cyclosporine?
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
What kind of molecule is tacrolimus?
macrolide antibiotic
29
What kinds of transplants is tacrolimus approved for?
kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, bone marrow and limb.
30
What is the mechanism of tacrolimus?
It binds to immunophillin FKBP-12 to inhibit calcineurin
31
What are the side effects of tacrolimus?
infection, HTN, abnormal renal function, acne, hair growth, diabetes
32
What kind of drug is Sirolimus (rapamycin)?
antiproliforative, antimetabolic
33
What kind of molecule is Sirolimus?
Macrolide antibiotic
34
What kind of molecule is Everolimus?
antiproliferative, antimetabolic | methyl derivative of sirolimus
35
What class of drugs does Mycophenolate Mofetil (Cell Cept) belong too?
Antiproliferative, antimetabolite
36
Is Sirolimus nephrotoxic?
No
37
Can you use Sirolimus in lung and heart transplants?
NO
38
Why is mycophenolate mofetil an effective antiproliferative?
It blocks the de novo synthesis of nucleotides, lymphocytes are very dependent on this type of synthesis to proliferate
39
What is the mechanism behind mycophenolate mofetil?
It is a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH)
40
Which type of IMPDH is mycophenolate mofetil specific for?
type 2 in lymphocytes
41
Why is mycophenolate mofetil an effective antiproliferative?
It blocks the de novo synthesis of nucleotides, lymphocytes are very dependent on this type of synthesis to proliferate
42
What kind of drug is azathioprine (Imuran)?
antiproliferative more toxic less specific for lymphocytes
43
how does methotrexate work?
Dihydrofolate reductase inhibitor that blocks thymidine biosynthesis antitumor agent
44
What is an example of an off label immunosupressant?
Cytotoxic and antimetabolic agents used in cancer
45
What kind of drug is Balatacept (Nulojix)?
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
how does methotrexate work?
Dihydrofolate reductase inhibitor that blocks thymidine
47
How does leflunomide work?
Dihydrooratate dehydrogenase inhibitor blocks denovo synthesis of UMP
48
What kind of drug is Balatacept (Nulojix)?
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
What is rituximab?
Rituxan | chimeric monoclonal Ab against APC CD20 (B Cells)
50
What is eculizumab?
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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