L65 Flashcards Preview

P&T Block 5 Renal > L65 > Flashcards

Flashcards in L65 Deck (34)
1

What are the 3 signals required for activation of T cells by APCs?

APC gets antigen -> draining LN
1. MHC2 + TCR (CD4)
MHC 1 + Tc (CD8)
2. Costim B7 on APC + CD28 on T cell
3. T cell produce IL2 that act paracrine to turn it on

2

What is the purpose of induction chemotherapy for transplant?

Reduce acute rejection
Deplete T cell so can't respond to the donor antigens

3

What are the 2 induction agents that deplete T cells?

ATG = anti-thymocyte globulin
Alemtuzumab

4

What is the induction agent that does not deplete T cells?

Basiliximab - Ab vs IL 2 receptor
No signal 3 for T cell activation

5

What are the 2 toxicities of ATG therapy?

TCP
Leukopenia
AKA drop platelets and T cells... duh... common SE to all these drugs
So you're watching for infection - prophylactic antibiotics

6

What are your 2 drugs of choice for initial immuno-suppression in setting of transplant?

Calcineurin inhibitors
1. Cyclosporine
2. Tacrolimus
Mechanism = prevent IL 2 transcription

7

Toxicity of both calcineurin inhibitors

Nephrotox - if use this for immune suppression in transplant of other organs, develop CKD over time
↑K
↓Mg + PO4
Thrombotic microangiopathy

8

2 SE tacrolimus

Alopecia - can't tack on that lost hair!
**Post-transplant diabetes

9

SE cyclosporine

Gingival hyperplasia
↑ hair - male pattern

10

What is the normal fxn of calcineurin?

TCR gets bound - activates calcineurin to turn NFAT-P = NFAT
NFAT required for IL2 transcription

11

Architecture changes to kidney on calcineurin inhibitors

Stripes of fibrosis

12

Mechanism of anti-metabolite agents

Inhibit T cell prolif by blocking nucleotide synthesis
Aka stop G1 -> S progression (after IL2 binds - activates TOR - then would normally undergo cell cycle)

13

What are the 2 anti-metabolites you need to know? What is the difference in their mechanism?

Azathioprine = "azothio-purine" = X purine recycling/synthesis
vs
Mycophenolate mofetil = MMF = inhibits de novo purine synthesis

14

Why do you avoid azathioprine in gout patients?

Azathioprine is broken down by xanthine oxidase
Your gout pt is probably on ALLOPURINOL = xanthine oxidase inhibitor to ↓uric acid levels
Gout pts can't breakdown azathiprine = ↑SEs

15

Biggest SE/concern with azathioprine

Sensitize to UV radiation
↑↑risk skin cancer

16

Mechanism of glucocorticoids for immune suppression

XNfKB - X IL2
↓T + B cell production

17

SE glucocorticoids

**Osteoporosis
**Diabetes (hyperglycemia)
AVN
Cushing features: central obesity, muscle breakdown
Cataracts
HTN

18

What is steroid withdrawl vs avoidance?

It is easier to pull pts off steroids who have been on them short term
If you have long term users, higher change of rejection if take off glucocorticoids

19

What is the mechanism of mTOR inhibitors?

Block T cell response to binding IL 2 (aka progressing into cell cycle)

20

2 mTOR inhibitors

Sirolimus = rapamycin
Everolimus

21

SE sirolimus

**Delayed wound healing - not right after OR
Insulin resistance
↑Cholesterol
TCP, leukopenia, anemia...

22

Mechanism of belatacept

Block costim via CD28 (2nd signal)

23

SE belatacept

↑post-transplant lymphoma - esp CNS lymphoma
Not going to give to a sero-neg EBV pt

24

Initial immune suppression regimen in adult kidney transplant pts

Tacrolimus = calcineurin I
+
MMR = mTOR block

25

Induction agent used at time of kidney transplant

T cell depleters: ATG or Alemtuzumab

26

How are the calcineurin Is broken down - which enzyme? Which drugs would ↑ vs ↓ their metabolism?

Tacrolimus + cyclosporine via CYP3A4 in liver
Drugs that ↓enzyme = ↑immune suppression
1. CCBs = dilitizaem, verapamil
2. Azoles
3. Antibiotics - mycins
Drugs that ↑enzyme = ↓IS *worry about rejection*
1. Rifampin (rifle)
2. Phenytoin (seizures)
3. Phenobarbital (barbituate)
4. St. John's Wart

27

How treat rejection?

Intensify IS:
+ Prednisone
Thymoglobulin
IVIg if Ab mediated rejection

28

Treat transplant pt with CMV infection

Present w/ flu-like symptoms
Stop anti-prolif agent
Immune system will take care of it

29

Treat BK/JC virus in transplant pt

Presentation of BK is asymptomatic - watch Cr for ↑
Prevention = monitoring
↓IS

30

Which drugs do you use in pregnancy for IS?

Cyclosporine/tacrolimus
Azathiprine
Prednisone

31

Drug that causes pneumonitis

Sirolimus (X mTOR)

32

Drug that causes vision changes

Cataracts = glucocorticoids

33

Drug class most likely to cause neutropenia/leukopenia

All but esp anti-metabolites
- Azathiopurine

34

Drug that causes proteinuria + oral ulcers

Sirolimus (X mTOR)