Immunosuppressants

Question 1

Antithymocyte globulin drug class

Answer 1

Polyclonal IgG

Question 2

Muromanab-CD3 class

Answer 2

co-stimulatory molecules

Question 3

Belatacept class

Answer 3

co-stimulatory molecules

Question 4

Daclizumab drug class

Answer 4

CD25 inhibitors

Question 5

Basiliximab drug class

Answer 5

CD25 inhibitors

Question 6

Alemtuzumab drug class

Answer 6

CD52 inhibitors

Question 7

Cyclosporine class

Answer 7

Calcineurin inhibitors

Question 8

Tacrolimus drug class

Answer 8

Calcineurin inhibitors

Question 9

Pimecrolimus drug class

Answer 9

Calcineurin inhibitors

Question 10

Methylprednisolone drug class

Answer 10

Steroids/nuclear transcription inhibitors

Question 11

Mycophenolate mofetil class

Answer 11

cell cycle disruptors

Question 12

Azathioprine class

Answer 12

cell cycle disruptors

Question 13

Methotrexate class

Answer 13

cell cycle disruptors

Question 14

Cyclophosphamide class

Answer 14

cell cycle disruptors

Question 15

Name some drug classes used for maintenance transplant therapy

Answer 15

Calcineurin inhibitors, anti-proliferatives, steroids

Question 16

What is the order of transplant organs to generate a rejection response?

Answer 16

Lung > heart > kidney > liver

Question 17

Describe organ responses to immunopharmacologic agents

Answer 17

Renal - very good; heart - good; liver - fair; bone marrow - good

Question 18

Describe common issues for antibody immunosuppressants

Answer 18

1) Opportunistic infections; 2) Need anti-infective prophylaxis; 3) Malignancy/LPD; 4) Cytokine-release syndrome

Question 19

Muromanab target

Answer 19

CD3

Question 20

Belatacept target

Answer 20

CD80/86 (B7)

Question 21

CD25 is also known as

Answer 21

IL-2 receptor

Question 22

Daclizumab target

Answer 22

Il-2 receptor (CD25)

Question 23

Basiliximab target

Answer 23

IL-2 receptor (CD25)

Question 24

Alemtuzumab target

Answer 24

CD52

Question 25

Cyclosporine target

Answer 25

Cyclophilin

Question 26

Tacrolimus target

Answer 26

FKBP12

Question 27

Sirolimus target

Answer 27

FKBP12

Question 28

Sirolimus class

Answer 28

mTOR inhibitors

Question 29

Mycophenolate target

Answer 29

inosine monophosphate dehydrogenase

Question 30

Azathioprine target

Answer 30

Metabolite blocks DNA synthesis and induces apoptosis

Question 31

Methotrexate target

Answer 31

Dihydrofolate reductase

Question 32

If lactating, the patient should avoid these immunosuppressants

Answer 32

Cyclophosphamide; methotrexate; azathioprine; tacrolimus; cyclosporine

Question 33

Globulin immunosuppressants are all lymphocyte depleting, except for this class of them (give drug members)

Answer 33

CD25 inhibitors Daclizumab and Basilixiumab

Question 34

Calcineurin inhibitors MOA

Answer 34

Inhibit first phase of T cell activation (IL-2 and IL-4 production)

Question 35

mTOR inhibitors MOA

Answer 35

Inhibits 2nd phase of T-cell activation; prevents B-cell differentiation and decreases IgM, IgG, IgA

Question 36

Cyclosporine MOA

Answer 36

Binds to cyclophilin and together inhibits calcineurin which is required for IL-2 transcription

Question 37

Tacrolimus MOA

Answer 37

Binds to FKBP12 (similar to cyclophiln) which is required for IL-2 transcription

Question 38

Calcineurin inhibitors side effects

Answer 38

Nephrotoxicity; hypertension; secondary malignancies

Question 39

Sirolimus MOA

Answer 39

Binds FKBP12 and together complexes with mTOR (whereas cyclosporine binds with calcineurin)

Question 40

Sirolimus side effects

Answer 40

Hyperlipidemia; thrombo-problems; azotemia; drug target is expressed widely so variety of problems

Question 41

Azathioprine side effects

Answer 41

Bone marrow suppression; secondary malignancies; avoid if lactating; lowers INR (Warfarin complication)

Question 42

How does azathioprine work?

Answer 42

It's a purine analog so it inhibits DNA replication and RNA production, selectively in lymphocytes for the most part

Question 43

Mycophenolate mofetil MOA

Answer 43

Metabolite is a nucleotide analog that inhibits DNA/RNA synthesis by halting G-MP production; more selective for lymphocytes than azathioprine so it is preferred over it now

Question 44

Mycophenolate mofetil side effects

Answer 44

GI issues (diarrhea; N/V; abdominal pain...)

Question 45

These drugs are used to treat acute rejection

Answer 45

Antithymocyte globulin; muromanab; methylprednisolone

Question 46

Muromonab MOA

Answer 46

Binds to CD3 (TCR signal transduction unit) and destroys T-cell activity

Question 47

These mABs can cause cytokine release upon infusion

Answer 47

Muromonab and Alemtuzumab (so watch for anaphylaxis)

Question 48

Daclizumab and Basiliximab MOA

Answer 48

Bind to IL-2 receptor

Question 49

This drug is used to prevent immune responses from coronary stents

Answer 49

Sirolimus

Question 50

Methylprednisolone/corticosteroids MOA

Answer 50

Inhibits transcription of pro-inflammatory factors esp. IL-2 by binding to cytosolic receptors, translocating to nucleus, and inhibit HAT (histone acetyltransferase) directly and by activating HDAC to reverse acetylation (of these pro-inflamm genes)

Question 51

What does mTOR normally do?

Answer 51

Part of clonal expansion pathway downstream from IL-2 receptor stimulation

Question 52

Alemtuzumab MOA

Answer 52

Anti-CD52 antibody targets T-cell for antibody/complement destruction

Question 53

Atgam MOA

Answer 53

Polyclonal IgG opsonizes human T-cells for complement destruction

Question 54

Atgam generic name

Answer 54

Anti-thymocyte globulin (polyclonal IgG anti-T-cell)

Question 55

Corticosteroids side effects

Answer 55

Cell-surface receptor targets -> rapid neurological issues (insomnia, depression); protein metabolism issues (impaired wound healing, stunted growth); susceptibility to infection (esp TB); hypercholesterolemia; thromboembolism; hypercorticism; aggravation of DM

Question 56

mTOR inhibitor side effects

Answer 56

Stunts proliferation of other cell types, inc. smooth muscle cell, hepatocyte, fibroblast bc mTOR is widely expressed in body