Regal- Anti-inflammatory Steroids and Immunosuppressives

Question 1

What drugs are anti-inflammatory steroids (glucocorticoids)?

Answer 1

Cortisol
Hydrocortisone
prednisone
methylprednisone
betamethasone
desamethasone

Question 2

What is the MOA of glucocorticoids?

Answer 2

Block steroid receptors that normally stimulate pathways that increase transcription of pro-inflammatory cytokines

• decrease COX2 expression (preferentially over COX 1)
• Inhibit AA release from phospholipids, affecting PG & LT formation
• Inhibit mast cell & basophil degranulation
• Inhibit synthesis & release of TNF (cachectin), IL-1, IL-2 & IFN → less immune cells circulating/functioning

Question 3

How are glucocorticoids eliminated?

Answer 3

M: liver

E: renal

Question 4

What toxicities are associated w/ glucocorticoids?

Answer 4

systemic therapy–> increased susceptibility to infections and OSTEOPOROSIS

Question 5

What glucocorticoid has a short t 1/2?

Answer 5

Hydrocortisone

Question 6

What glucocorticoids have intermediate t 1/2?

Answer 6

Prednisone

methylprednisone

Question 7

What glucocorticoids have long t 1/2?

Answer 7

Betamethasone

Dexamethasone

Question 8

What SE are associated w/ glucocorticoids?

Answer 8

• Peptic ulceration
• Behavioral disturbances
• Cataracts
• Inhibition of growth

Discontinuation of long term use → adrenal insufficiency (fever, myalgia, arthralgia, malaise, death d/t hypotension & shock)

Question 9

What glucocorticoid is good for tx ITP, AHA, acute glomulonephritis, autoimmune disease ?

Answer 9

Prednisone

Question 10

What glucocorticoids have the best anti-inflammatory properties?

Answer 10

Betamethasone

dexamethasone

Question 11

What drugs are the three categories of immunosuppressive drugs?

Answer 11

calcineurin inhibtors
anti-proliferative
Abs

Question 12

What drugs are calcineurin inhibitors?

Answer 12

cyclosporine

tacrolimus

Question 13

What is the MOA of cyclosporine?

Answer 13

Binds cyclphillin to inhibit calcineuran phosphatase activity>
blocks cytokine gene expression and T cell activation

Question 14

How is cyclosporine eliminated?

Answer 14

Extensive liver metabolism

Question 15

What are the SE associated w/ cyclosporine?

Answer 15

drug interactions

nephrotoxicity (75% of pts)

Question 16

What is the MOA of tacrolimus?

Answer 16

Binds FKBP to inhibit mTOR >
blocks cell cycle progression
(G1/S)

Question 17

What SE are assoicated w/ tacrolimus?

Answer 17

nephrotoxicity

Question 18

What drugs are anti-proliferative?

Answer 18

sirolimus (rapamycin)

mycophenolate mofetil

Question 19

What is the MOA of siroliums?

Answer 19

Binds to FKBP to inhibit mTOR → blocks cell-cycle progression
(G1/S)

Question 20

What are the SE of sirolimus?

Answer 20

Dose dependent increase in cholesterol and triglycerides
Nephrotoxicity w/ cyclosporine
CYP34A drug intrxns

Question 21

What drug is used in combination therapy for organ transplant rejection?

Answer 21

sirolimus

Question 22

What is the MOA of mycophenolate?

Answer 22

Inhibits IMPDH in de novo guanine nucleotide synth pathway → blocks B & T cell proliferation preferentially

Question 23

What are the SE of mycophenolate?

Answer 23

Hematological : leukopenia

GI: diarrhea, vomiting

Question 24

When is mycophenolate used?

Answer 24

organ transplant

Question 25

What drugs are Abs?

Answer 25

anti-thymocyte globulin muromonab-CD3 Daclizumab Basiliximab

Question 26

What is the MOA of ANti-thymocyte globulin?

Answer 26

Binds thymocytes in the circulation → lymphopenia & impaired T cell immune responses

Question 27

What are the SE of anti-thymocyte globulin?

Answer 27

Serum sickness Nephritis Anaphylaxis rare

Question 28

What is the MOA of muromonab CD-3?

Answer 28

Binds ε chain of CD3 of T-cells → TCR is internalized → prevents Ag recognition

Question 29

What are the SE of muromonab CD-3?

Answer 29

Cytokine release syndrome: mild flu like illness to life-threatening shock *Reduced w/ glucocorticoid admin 1st

Question 30

How is muromonab CD-3 used?

Answer 30

to prevent Acute rejection of kidney, liver, heart transplants

Question 31

What is the MOA of daclizumab and basiliximab?

Answer 31

Anti- IL-2 receptor (CD25) → block IL-2 mediated T-cell activation events

Question 32

What are the SE of Daclizumab and basiliximab?

Answer 32

NO cytokine release syndrome | Anaphylaxis

Question 33

What drugs are commonly used in organ transplantation?

Answer 33

Daclizumab | Basiliximab

Question 34

Which drugs have a lower incidence of lymphoproliderative disorders & opportunistic infections than most other immunosuppressant drugs?

Answer 34

Daclizumab | Basiliximab