Immunomodulatory Drugs

Question 1

Cyclosporine (CsA)

Answer 1

Calcineurin inhibitor. Inhibits activation of CD4+ and CD8+ T cells. Binds with cyclophilin, this complex inhibits calcineurin and stops IL-2 transcription. DMARD for RA. CYP3A4 metabolism, 3A4 inhibition leads to decreased CsA clearance and increased activity.

Question 2

Tacrolimus

Answer 2

Fujimycin. Calcineurin inhibitor, much more potent than cyclosporine with less nephrotoxicity. Used in transplant rejection, GVHD.

Question 3

Sirolimus

Answer 3

Rapamycin. Inhibits mTOR, blocks protein synthesis triggered by IL-2. As effective as CsA for renal transplant but NO NEPHROTOXICITY. Causes anemia, thrombocytopenia. Not for lung or liver transplants.

Question 4

Mycophenylate Mofetil (MMF)

Answer 4

Hydrolized to MPA in liver, this stops de novo purine synthesis. Most T and B cell purine synth is denovo, not salvage. Combined with CsA/tacrolimus in kidney/liver transplants to allow reduced calcineurin inhibitor dose and reduce nephrotoxicity.

Question 5

Azathioprine

Answer 5

Purine analog, disrupts de novo purine synth and stops transcription. Combined with calcineurin inhibitors to reduce rejection and treat severe RA.

Question 6

Methotrexate

Answer 6

Folate analog, competes for and competitively inhibits dihydrofolate reductase.

Question 7

Sulfasalazine

Answer 7

Scavenges ROS produced by neutrophils thereby diminishing their damaging effects. Sulfa-scavenger.

Question 8

Penicillamine

Answer 8

Prevents IL-1 generation and collagen maturation, treats RA. PenicIL kILls IL-1. IL IL IL.

Question 9

Chloroquine

Answer 9

Stops lysosomal processing and antigen presentation, decreases T-cell activation. Anti-malarial drug, combined with methotrexate and sulfasalazine to treat RA.

Question 10

Leflunamide

Answer 10

Inhibits dihydroorotate dehydrogenase, blocking pyrimidine synthesis. Left-rotation, lefl. blocks rotate.

Question 11

Daclizumab

Answer 11

CD-25. Targets CD-25 on IL-2 receptor, thereby inhibits IL-2 mediated T-cell activation.

Question 12

Basilixumab

Answer 12

CD-25. Targets CD-25 on IL-2 receptor, thereby inhibits IL-2 mediated T-cell activation.

Question 13

Infliximab

Answer 13

TNF-α. Increased infection susceptibility. TNF-α: AEI: Adalimumab, Etanercept, Infliximab.

Question 14

Etanercept

Answer 14

TNF-α. Increased infection susceptibility. TNF-α: AEI: Adalimumab, Etanercept, Infliximab.

Question 15

Adalimumab

Answer 15

TNF-α. Increased infection susceptibility. TNF-α: AEI: Adalimumab, Etanercept, Infliximab.

Question 16

Abatacept

Answer 16

Immunoglobulin against CTLA4, treats RA.

Question 17

Muromonab

Answer 17

CD3. Targets CD3, treats rejection in heart, liver, kidney transplants. Not given prophylactically, only given after rejection is seen.

Question 18

Anakinra

Answer 18

IL-1R, treats RA. Increased risk of infections, as with pretty much all the mAb’s.

Question 19

Tocilizumab

Answer 19

IL-6R. Treats RA, increased infection risk.

Question 20

Rituximab

Answer 20

CD 20, treats RA. B cell depleting Ab.

Question 21

Natalizumab

Answer 21

VLA4, blocks T cell migration to site of infection. Crohn’s disease and multiple sclerosis. High risk of progressive multifocal leukoencephalopathy (PML).

Question 22

IV Immunoglobulin

Answer 22

Pooled Ig’s of healthy donors, confers passive immunity and has anti-inflammatory effect.

Question 23

Fingolimod

Answer 23

Prevents lymphocytes from leaving the lymph nodes by binding to sphingosine-1 phosphate receptors. Treats MS. Risk of fatal infections since T cells can’t leave the lymph node to fight infection.

Question 24

IFN-β

Answer 24

Treats MS.

Question 25

Epoetin alfa

Answer 25

Stimulates RBC production, treats anemia.

Question 26

Darbepoetin alfa

Answer 26

Hopefully the same as epoetin alfa.

Question 27

Filgastrim

Answer 27

Stimulates neutrophil proliferation, maturation, and migration.

Question 28

Belimumab

Answer 28

BAFF, depletes B cells. Treats SLE.