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Flashcards in 2: Immunosuppressants Deck (54)
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1

what does immunopharmacology involve?

-production of vaccines and immunization
-treatment of inflammation
-autoimmune disorders
-allergies
-fungal, viral, and bacterial infections
-infections due to parasites
-cancer

2

what induces autoimmune diseases?

hyperactive T cell immune response

3

what causes immune suppression and incompetence?

hypoactive response of T cell immunity

4

role of each:
-helper T cells
-cytotoxic T cells
-suppressor T cells

helper: coordination of immune response
cytotoxic: remove virus-infected cells from the body
suppressor: temper immune response when it's overactive

5

purpose of immunosuppressants

inhibit normal immune response following organ transplantation or overactive immune response associated with autoimmune disorders

6

what part of the immune response do immunosuppressants work best for?

primary immune response
-efficacy depends on the type of immune response
-best results when treatment begun before exposure to Ag

7

define acute rejection

-occurs 24h to weeks post transplant
-mediated by T cells and cytokine release

8

how is immunosuppression achieved?

different classes of immunosuppressants that:
-decrease amount of lymphocytes
-divert lymphocyte traffic
-block pathways involved in lymphocytic response

9

classes of immunosuppressants

1. regulators of gene expression
2. alkylating agents
3. inhibitors of de novo purine synthesis
4. inhibitors of de novo pyrimidine synthesis
5. kinase and phosphatase inhibitors
6. protein immunosuppressants
7. others

10

what drugs are regulators of gene expression?

adrenocortical steroids - prednisone, prednisolone

11

what parts of immunosuppression are adrenocortical steroids used for?

induction and maintenance therapy

12

function of adrenocortical steroids

-reduce circulating lymphocyte levels
-block lymphocyte activation required for Ag presentation
-block T cell proliferation

(inhibit IL-2 gene expression, which is required for clonal expansion of B and T cells)

13

what drugs are alkylating agents?

cyclophosphamide

14

what drugs are inhibitors of de novo purine synthesis?

azathioprine, 6-mercaptopurine (first gen)
mizoribine, mycophenolate mofetil (MMF) (second gen)

15

what parts of immunosuppression are alkylating agents and purine synthesis inhibitors used for?

induction and maintenance

16

function of alkylating agents and purine synthesis inhibitors

-block or interfere with DNA/RNA synthesis and function
-prevent clonal expansion of B and T cells

17

chemically describe MMF

-ester prodrug -> active form: mycophenolic acid

18

function of MMF

inhibits inosinse 5'-monophosphate DH

19

side effects of MMF

GI shit and events related to bone marrow suppression (leukopenia, anemia, thrombocytopenia)

does NOT have CV risk or chronic nephrotoxic secondary effects

20

what drugs are inhibitors of de novo pyrimidine synthesis?

-brequinar
-leflunomide
-malononitrilamides

21

MOA of de novo pyrimidine synthesis

inhibit dihydroorotate DH

22

usefulness of the leflunomide derivative, FK778?

no benefit for using FK778 over MMF - also seems more difficult for patients to tolerate

23

what drugs are kinase and phosphatase inhibitors?

cyclosporine
tacrolimus
sirolimus/rapamycin

24

what parts of immunosuppression are kinase and phosphatase inhibitors used for?

induction and maintenance therapy (block signaling pathways that stimulate IL-2 production)

25

where does cyclosporine come from?

the fungus Tolypocladium inflatum Gams

26

how is cyclosporine administered? dosing?

IV or p.o.
given 4-24h before transplant, continued after with lower doses at weekly intervals

27

where does cyclosporine concentrate?

in the red and white blood cells

28

PK of cyclosporine

metabolized by liver
mainly excreted in feces

29

toxicity of cyclosporine

renal (proximal tubule) - limiting factor
gingival (hyperplasia)
neuronal
some hepatic
may induce systemic HTN

30

MOA of cyclosporine

associates with calcineurin and inhibits its phosphatase activity, preventing translocation of NFAT members to nucleus, inhibiting production of lymphokines

also blocks JNK and p38 signaling pathways that are induced by antigen recognition in T cells