Inflammation Terlecky 2

Question 1

What are the classes of immune system drugs?

Answer 1

Glucocorticoids, immunophilin ligands, cytotoxic agents, antibodies/biologics

Question 2

What is the net result of corticosteroid action?

Answer 2

anti-growth, anti-inflammation, immunosuppression (suppressed production of proinflammatory prostaglandins, leukotrienes, thromboxanes, platelet activating factor)

Question 3

Where is prednisone metabolized?

Answer 3

LIVER! to its active form prednisolone. unless extreme cirrhosis these are =

Question 4

Complications of chronic glucocorticoid use???

Answer 4

• Cushings syndrome!
• Cataracts! increased pressure
• Accel artherosclorosis,HT
• GI and peptic ulcer disease
• osteoporosis
• decreased immune response
• amenorrhea/infertility

Question 5

What are the two calcineurin inhibiting agents?

Answer 5

Cyclosporine and Tacrolimus
cyclo binds to cyclophilins
tacro binds to FKBPs

Question 6

How do calineurin inhibiting agents immunosuppress?

Answer 6

Immunophilin-drug complex binds to calcineurin (a phosphatase) SO it cannot dephosphrylate nuclear factors of activated T cells….
SO reduced transcription of early cytokine gene IL2 (most important)

Question 7

When are calcineurin inhibiting agents effective?

Answer 7

Only before response is initiated. Drugs are NOT effective in halting the amplification of the immune response after amp.

Question 8

The main side effect of calcineurin inhibit =

Answer 8

NEPHROTOXICITY!!

also ade b/c 3A4

Question 9

What class of drug is Sirolimus?

Answer 9

Non-calcinuerin inhibiting agent

Question 10

What is the MOA of Sirolimus?

Answer 10

Interferes with the signal transduction pathways elicited by IL2. binds to FKBP but DOES NOT inhibit calcineurin.

mTOR inhibited so T Cells arrest in G1.
cyp 3A4 elimination

Question 11

Four anti-metabolite immunosuppressive agents are?

Answer 11

Azathioprine, methotrexate, mycophenolate mofetil, leflunomide

Question 12

The active components of Azathioprine function by…

Answer 12

decreasing purine synthesis so RNA production is decreased. Decreased B and T lymphocytes, decreased immunoglobulin production, decreased IL2 secretion.

Question 13

MAJOR potential drug interaction of Azathiorpine?

Answer 13

LETHAL amount of bone marrow aplasia if taken with ALLOPURINOL

Question 14

What drug binds to dihydrofofolate reductase?

Answer 14

Methotrexate… severe toxicity!

Question 15

What is the MOA of mycophenolate Mofetil

Answer 15

Blocks De Novo purine synthesis so decreases lymphocyte proliferation and response to antigenic/mutagenic stimuli.
DECREASE GTP POOLS in lymphs and monos.
no IL1/IL2 effects!!!

Question 16

What drug inhibits pyrimidine synthesis?

Answer 16

Leflunomide

Question 17

What are the three potential drug interactions of cyclophosphamide?

Answer 17

1. 3A4
2. Prolonged NM blockade with succinylchoine (blocks enzymatic breakdown)
3. TCA decrease bladder emptying and increase exposure to metabolite acrolein

Question 18

What are the anti tumor necrosis factor agents (3)?

Answer 18

Adalimumab, infliximab, etanercept