Immunosuppressive Drugs Flashcards Preview

IHO Week 6 > Immunosuppressive Drugs > Flashcards

Flashcards in Immunosuppressive Drugs Deck (39):
1

Which are more effectively suppressed: primary or secondary immune responses?

primary

2

Is imune suppression more likely to occur if you start therapy before exposure or after exposure?

before exposure

3

Immunosupression increases the risk of what?

infection, lymphomas

4

What are the four major calsses of immunosuppressive drugs?

glucocorticoids
calcineurin inhibitors
antiproliferative/antimetabolic drugs
antibodies

5

What are the three primary uses of immunosuppression?

Autoimmune disease, transplanation, hemolytic anemia of the newborn

6

What are the two classes of steroids synthesized by the adrenal cortex?

glucocorticoids and mineralocorticoids

7

What's the main endogenous glucocorticoid? mineralocorticoid?

gluco = hydroxortisone (cortixol)
mineral = aldosterone

8

Which one is anti-inflammatory?

glucocorticoids

9

What are the four synthetic steroids we need to know that are used as anti-inflammatory drugs?

betamethasone
dexamethasone
methylprednisolone
prednisone

10

Where are the receptors for steroids?

NOT on the plasma membrane - in the cytosol and then they dimerize and go to the nucleus

11

Why are the effects of steroid usually delayed?

because they alter gene transcription, which taikes a while

12

What are steroid effects on neutrophils/

release from marrow is accelerated and half time in circulation is increased, so you get more circulatin, HOWEVER< there's a blockage of the neutrophil migration into inflammatory sites, so there are more but they can't do their job

13

What are steroid effects on lymphocyts?

profound transient lymphopenia
the cells aren't lysed, but move to extracellular compartments like the spleen, LNs, htoracic duct and bone marrow

14

What are the steroid effects on monocytes and eosinophils?

decreased in peripheral blood

15

Which COX is more inhibited by steroids?

COX 2 (reduced expression)

16

How do steroids inhibit prostaglandin and leuketriene formation (beyond just inhibiting COX)?

They inhibit the release of AA form phospholipids

17

What effect do steroids hae on mast cells and basophils?

inhibit degranulation

18

True of false: the negative side effects of steroids start to occur with the first dose?

false - one dose is totally harmeless
a few days is likely not harmful except at high doses

19

Abrust cessation of prolonged high dose steroids will increase risk of organ failure?

renal insufficiency

20

What are the adverse effects of continued use?

immunosuppression
peptic ulceration
behavioral disturbances
cataracts
osteoporosis and compression factors
inhibition of growth

21

The withdrawal is associated with adrenal insufficiency - what adverse effects relfect this?

fever, myalgia, arthralgia, malaise, death with hypotension and shock!

22

What does cyclosporine bind to? To inhibit what?

binds to cyclophilin to inhibit calcineurin activity and blocks the dephosphorylation event critical for cytokine gene expression and T cell activation

23

What's the most common use for cycloposinr?

long term therapy after transplantation

24

WHat's the major adverse effect of cyclosporine?

renal toxicity - in as many as 75% of patients!

25

What does Tacrolimus bind to to inhibit clacineurin?

FK binding protein (FK506)

26

Which is more potent: cyclosporine or tacrolimus?

tacrolimus - 100 time more!

27

What are the two antiproliferative/antimetabolic drugs we need to know?

sirolimus and mycophenolate mofentil

28

What is the mechanism of action for sirolimus?

it binds to the FKBP to inhibit mTOR, which blocks cell ccycle progression from G1 to S phase

29

What's the toxicity for sirolimus?

dose dependent increase in cholesterol and triglycerides
nephrotoxicity if given with cyclosporin
increased risk of lymphomas and infections
substrate for CYP3A4 - drug interactions

30

What is the mechanism of action for mycophenolat emofentil?

A metabolite of the drug is an inhibitor of inosine monophosphate dehydrogenase which is required for de novoguanine nucleotide synthesis

31

What are the toxicities for mycophenolate?

leukopenia, diarrhea, vomiting

32

What are the four antibodies we need to know for immunosuppression?

Anti-thymocyte globulin
muromonab - CD3
daclizumab
basiliximab

33

What do the anti-thymocyte globulins do?

like the name suggests...
they bind to thymocytes in the circulation, resultin gin lymphpenia and imparied T CELL RESPONSE

34

What does muromonab-CD3 do?

like the name suggests...
binds to the epsilon chain of CD3 glycoprotein of the TCR complex on T cells, which makes the TCR be internalized, preventing further antigen recognition

35

When is muromonab CD3 usually used?

to prevent kidney, liver or heart transplant rejections

36

The initial interaction of muromonab CD3 with the TCR causes what?

cytokine release and cytokine release syndrome
(because you get a combo of Fc receptor mediated crosslinking, resulting in the initial activation of the cell and release of cytokines)

37


Why is repeated use contraindicated with muromonab?

it's a mouse monoclonal antibody, so you get immune respnse to is over time

38

What do daclizumab and basiliximab do?

They are anti-IL2 antibodies that bind to the receptor presented on ACTIVATED T cells, thus inhibiting IL-2 mediated activation events

39

Are daclizumab and basiliximab better or worse in terms of side effect profile?

better - no cytokine release syndrome, lower incidence of lymphoproliferative disorders/infections