Immunosuppressive Agents

Question 1

Indications for Induction Immunosuppressive Drugs?

Answer 1

transplant- organ, bone marrow
autoimmune conditions- SLE, RA
chronic rejection
Hypersensativity/Inflamm diseases- asthma, atopic dermatitis

Question 2

mechanism of hyperacute rejection?

Answer 2

pre-formed antibodies
allo-antibodies (anti-MHC1)
within minutes

Question 3

mechanism of acute rejection?

Answer 3

Cell-mediated (CD8)
antibody mediated
1-4 weeks later

Question 4

mechanism of chronic rejection?

Answer 4

Cell-mediated (CD8)
antibody mediated
chronic renal allograft nephropathy
months-years laer

Question 5

Principles of Immunosuppression?

Answer 5

target and block signals at different stages of T-cell activation

Question 6

Induction immunosupp

Answer 6

intense, prophylactic
prevents acute rejection
at time of transplant
“puts immune system to sleep”

Question 7

maintenance immunosupp

Answer 7

less potent
given throughout life of transplanted organ
prevents late acute rejection and graft survival

Question 8

induction agents?

Answer 8

anti-lymphocyte globulin (thymoglobulin)
alemtuzumab
basiliximab
methylprednisone

Question 9

MOA muronamab

Answer 9

CD3 blocker- signal 1

Question 10

thymoglobulin MOA

Answer 10

“workhorse”

IgG antibodies bind T-cells, activate complement mediated cell lysis of circulation T-cells

Question 11

thymoglobulin toxicity

Answer 11

fever, rash, pruritis
serum sickness- 7-14 days after
thrombocytopenia
pre-medicate with tylenol, benedryl

Question 12

alemtuzumab MOA and tox

Answer 12

mab against CD52, used commonly with B-cell lymphoma

tox: injection site rxn, anemia, thrombocytopenia

Question 13

basiliximab MOA

Answer 13

binds alpha unit of IL2 receptor, inhibiting binding–> decreased activation
very well tolerated

Question 14

methylprednisone MOA

Answer 14

given in HIGH DOSE for INDUCTION
anti- inflammatory corticosteroid
blocks cytokine gene expression leading to decreased immune response
impair monocyte, macrophage function

Question 15

methylprednisone tox

Answer 15

HTN, HYPERGLYCEMIA
impaired wound healing, fluid retention
vivid dreams
Note: taper into oral prednison for maintenence

Question 16

Maintenance immunosupp drugs?

Answer 16

Tacromilus
Cyclosporine
Mycophenolate
Azathioprine
Siromilus
Everolimus
Prednisone

Question 17

Tacromilus MOA

Answer 17

Calcineurin inhibitors- inhibit calcineurin phosphatase by binding FKBP12- downstream of signal 1
leads to INHIBITION IL2 synthesis

Question 18

Tacromilus tox

Answer 18

alopecia, HYPERGLYCEMIA, hyperkalemia, NEPHROTOXICITY, FINE TREMOR at rest
CYP450 3A4 interactions

Question 19

Mycophenolate/azathioprine MOA

Answer 19

Anti-metabolite

Inhibits prolif of B and T cells by preventing RNA/DNA synthesis in nucleus

Question 20

Mycophenolate TOX

Answer 20

GI INTOLERANCE-diarrhea

Question 21

azathioprine tox

Answer 21

Hepatotoxicity- not used

elevated ALT/AST

Question 22

Sirolimus/Everolimus MOA

Answer 22

mTOR inhibition
Binds FKBP12- complex that inhibits target of rapamycin stopping prolif of B/T cells
inhibits IL2

Question 23

Sirolimus TOX

Answer 23

ANEMIA, hepatic artery thrombosis, hyperlipidemia, IMPAIRED WOUND HEALING, PROTEINURIA
CYP450 3A4 interactions

Question 24

prednisone MOA

Answer 24

LOW DOSE for maintenence-taper off

corticosteroid that blocks cytokine expression and decreases immune response

Question 25

prednisone TOX

Answer 25

HYPERGLYCEMIA, OSTEOPOROSIS (supplement Ca)

Question 26

Cyclosporine MOA

Answer 26

Calcineurin inhibitor- binds cyclophilin which inhibits calicineurin phosphatase, inhibiting IL2 synthesis

Question 27

Cyclosporine TOX

Answer 27

same as tacromilus, but less potent, and has HIRSUTISM and HYPERTrICHOSIS with less neurotox and hyperglycemia

Question 28

when would you use mTOR?

Answer 28

``` with delayed graft function until kidney function kicks in underlying renal insufficiency other drug intolerance calcineurin toxicity pancreas transplant ```

Question 29

typical maintenance regimen- kidney transplant?

Answer 29

tacromilus+mycophenolate+prednisone

Question 30

typical maintenance regimen- liver transplant?

Answer 30

tacromilus+mycophenolate+/-prednisone

Question 31

typical maintenance regimen- pancreas transplant?

Answer 31

tacromilus+ sirolimus OR mycophenolate | STEROID FREE b/c of HYPERGLYCEMIA RISK