Immunosuppressants

Question 1

Gluocorticoids MOA

Answer 1

Genomic: Bind to cytosolic receptor and translocating to nucleus to bind to DNA
Non-genomic: Insert themselves into cell membrane, influence signaling pathways, etc.

Question 2

Gluocorticoids MOA

Answer 2

Genomic: Bind to cytosolic receptor and translocating to nucleus to bind to DNA
Non-genomic: Insert themselves into cell membrane, influence signaling pathways, etc.

Question 3

Glucocorticoid effects

Answer 3

Rapid decrease in peripheral lymphocytes
Decrease pro-inflammatory cytokines=> IL-1, IL-6, TNFa, Infy
Inhibit IL-2 production by T cells
Little effect on humoral immunity

Question 4

Glucocorticoid therapeutic uses

Answer 4

Treat transplant rejection, usually co administered with something else
Treat graft vs host disease
Blocks first dose cytokine storm
Treat autoimmune disorders

Question 5

Glucocorticoids adverse

Answer 5

Increased risk of infection
Poor wound healing
HTN
Adrenal crisis upon discontinuation

Question 6

Low dose glucocorticoids

Question 7

Medium dose glucocorticoids

Answer 7

> 7.5 mg, but

Question 8

High dose glucocorticoids

Answer 8

> 30 mg, but

Question 9

Glucocorticoids pulse therapy

Answer 9

> 250 mg prednisone equivalent per day for 1 day or a few days

Question 10

Glucocorticoids pulse therapy

Answer 10

> 250 mg prednisone equivalent per day for 1 day or a few days

Question 11

Glucocorticoid effects

Answer 11

Rapid decrease in peripheral lymphocytes
Decrease pro-inflammatory cytokines=> IL-1, IL-6, TNFa, Infy
Inhibit IL-2 production by T cells
Little effect on humoral immunity

Question 12

Glucocorticoid therapeutic uses

Answer 12

Treat transplant rejection, usually co administered with something else
Treat graft vs host disease
Blocks first dose cytokine storm
Treat autoimmune disorders

Question 13

Glucocorticoids adverse

Answer 13

Increased risk of infection
Poor wound healing
HTN
Adrenal crisis upon discontinuation

Question 14

Low dose glucocorticoids

Question 15

Medium dose glucocorticoids

Answer 15

> 7.5 mg, but

Question 16

Azathrioprine class and MOA

Answer 16

Purine antimetabolite
Metabolized into 6-mercaptopurine->other metabolites, incorporated into DNA, inhibiting lymphocyte proliferation
Lymphocytes do not have a salvage pathway=>cannot compensate

Question 17

Very high dose glucocorticoids

Answer 17

> 100 mg prednisone equivalent per day

Question 18

Glucocorticoids pulse therapy

Answer 18

> 250 mg prednisone equivalent per day for 1 day or a few days

Question 19

Cyclosporine class and MOA

Answer 19

Calcineurin inhibitor
Suppresses T-cell mediated immunity by forming a complex w/ cyclophilin=>binds to and inhibits calcineurin=>IL-2 (T cell growth factor) is not produced

Question 20

Cyclosporine uses

Answer 20

Very effective for prophylaxis for organ transplants, except for renal transplants b/c it is nephrotoxic

Question 21

Cyclosporine adverse

Answer 21

Renal dysfunciton
HTN
Hyperlipidemia 
Swollen/painful gums
Hirsutism 
Do not drink grapefruit juice

Question 22

Tacrolimus class and MOA

Answer 22

Calcineurin inhibitor

same MOA as cyclosporine

Question 23

Tacrolimus uses

Answer 23

Prophylaxis of allograft rejection in solid-organ transplantation

Question 24

Sirolimus adverse

Answer 24

Anemia/leukopenia/thrombocytopenia
hypokalemia
GI
Increased risk of infections

Question 25

Azathioprine class adn MOA

Answer 25

Purine antimetabolite Metabolized into 6-mercaptopurine->other metabolites, inserts into DNA, inhibiting lymphocyte proliferation Lymphocytes do not have a salvage pathway=>cannot compensate

Question 26

Azathriopine uses

Answer 26

Prevention of organ transplant rejection Severe RA Some autoimmune disorders

Question 27

Azathriopine adverse

Answer 27

Bone marrow suppression=> leukopenia hepatotoxicity Increased susceptibility to infections

Question 28

Mycophenolate Mofetil MOA

Answer 28

MMF is a prodrug, hydrolezed to MPA=>selective inhibitor of an enzyme required for synthesis of guanine =>destroys de novo pathway

Question 29

Mycophenolate Mofetil uses

Answer 29

Transplant rejection | Lupus

Question 30

Mycophenolate Mofetil adverse

Answer 30

leukopenia Increased risk for CMV Congenital abnormalities

Question 31

Sirolimus MOA

Answer 31

Inhibits T-lymphocyte proliferation, blocks G1-S phase transition

Question 32

Sirolimus Uses

Answer 32

Prophylaxis for organ transplant rejection | In renal transplant for pts who cannot tolerate calcineurin inhibitors

Question 33

Sirolimus adverse

Answer 33

Anemia/leukopenia/thrombocytopenia hypokalemia GI Increased risk of infections

Question 34

Antithymocyte Globulin MOA

Answer 34

Contains antibodies from a rabbit that binds to things like CD3 (and much more CDs) to deplete human T lymphocytes

Question 35

Antithymocyte Globulin uses

Answer 35

Induction immunosuppression | Tx of acute reaction of solid organ transplants

Question 36

Antithymocyte Adverse

Answer 36

fevers, chills, malaise, hypotension due to release of cytokines (TNF-a)=> cytokine storm Serum sickness

Question 37

Murononab-CD3 MOA

Answer 37

Mouse antibody directed against CD3=> cause depletion of T lymphocytes

Question 38

Muromonab-CD3 uses

Answer 38

Reverse glucocorticoid resistant organ transplant rejection episodes Can only use this drug once!!

Question 39

Muomonab-CD3 adverse

Answer 39

cytokine storm | tremor, nausea, weakness

Question 40

Anti-TNFa reagants

Answer 40

Infliximab, adalimumab, and etanercept

Question 41

Anti-TNFa MOA

Answer 41

prevents TNFa form binding to its receptors by binding to it directly

Question 42

Infliximab

Answer 42

Monoclonal antibody that is part human and part murine (mouse)

Question 43

Adalimumab

Answer 43

Recombinant human IgG1 monoclonal antibody

Question 44

Etanercept

Answer 44

Part TNF-a receptor and part portion of human IgG1

Question 45

Anti-TNFa uses

Answer 45

RA Crohn's UC, spondylitis, etc

Question 46

Anti-TNFa adverse

Answer 46

Increased risk for infections, lymphomas, and other malignancies