immunosuppressants

Question 1

what are the indications for immunosuppressants?

Answer 1

transplantation - prophylaxis and acute rejection
autoimmune
inflammatory diseases

Question 2

what are the major classes of immunosuppressive agents?

Answer 2

glucocorticoids
calcineurin inhibitors
antiproliferative / antimetabolic agents
biologicals

Question 3

what are the adverse effects of immunosuppressive agents?

Answer 3

infectious disease

malignancy

Question 4

what are the calcineurin inhibitors?

Answer 4

cyclosporine

tacrolimus

Question 5

what are the antiproliferative / antimetabolic agents?

Answer 5

azathioprine
mycophenolate mofenil
sirolimus

Question 6

what are the biological immunosuppressants?

Answer 6

antithymocyte globulin
muromonab-CD3
anti-TNFa

Question 7

what are the general effects of glucocorticoids?

Answer 7

genomic - up to 1% of DNA influence via cytosolic receptors, inhibition of transcription factors

non-genomic - cell signaling pathways, cell membrane

Question 8

what are the key specific effects of glucocorticoids?

Answer 8

1. downregulation of proinflammatory cytokines (IL-1, IL-6)
2. inhibit IL-2 (anti-T cell proliferation)
3. decrease in peripheral WBCs
4. reduce neutrophil chemotaxis

Question 9

what are the adverse effects of glucocorticoids?

Answer 9

growth retardation 
increased risk of infection 
poor wound healing 
hypertension 
avascular necrosis of bone 
cataracts 
hyperglycemia 
adrenal crisis upon rapid discontinuation

Question 10

what is considered a low dose of glucocorticoid?

Answer 10

below 7.5 mg prednisone equivalent per day

Question 11

what is considered a medium dose of glucocorticoid?

Answer 11

7.5 - 30 mg prednisone equivalent per day

Question 12

what is considered a high dose of glucocorticoid?

Answer 12

30 - 100 mg prednisone equivalent per day

Question 13

what is considered a very high dose of glucocorticoid?

Answer 13

over 100 mg prednisone equivalent per day

Question 14

what is considered pulse therapy for glucocorticoid?

Answer 14

over 250 mg per day for 1 day or a few days

Question 15

what drug is the standard for glucocorticoid dosing regimens?

Answer 15

prednisone

Question 16

what is the MOA of cyclosporine?

Answer 16

1. suppresses T cell immunity
2. forms complex with cyclophilin, which then binds to calcineurin and eventually leads to prevention of transcription and translation of certain cytokines

Question 17

what is the main adverse toxicity associated with cyclosporine?

Answer 17

nephrotoxicity

Question 18

what is the preferred calcineurin inhibitor for transplantation due to ease of blood level monitoring?

Answer 18

tacrolimus

Question 19

what is the main therapeutic use for tacrolimus?

Answer 19

prophylaxis of allograft rejection in solid organ transplantation

Question 20

what are the main adverse effects of tacrolimus?

Answer 20

nephrotoxicity
HTN
diabetes
grapefruit

Question 21

what is the MOA of azathioprine?

Answer 21

1. metabolized to 6-mercaptopurine
2. metabolites incorporated into DNA
3. inhibition of lymphocyte proliferation (lymphocytes do not have a salvage pathway)

Question 22

what are the adverse reactions of azathioprine?

Answer 22

bone marrow suppression
hepatotoxicity
VZV, HSV

Question 23

what is the MOA of mycophenolate mofetil?

Answer 23

1. knock out de novo synthesis of guanine nts

2. inhibits lymphocyte proliferation

Question 24

what are the therapeutic uses for mycophenolate mofetil?

Answer 24

propylaxis for graft rejection

SLE

Question 25

what are the adverse reactions of mycophenolate mofetil?

Answer 25

hematologic GI contraindicated for pregnancy

Question 26

what is the MOA of sirolimus?

Answer 26

inhibits T cell proliferation via prevation of mTOR activation

Question 27

what drug has allowed combination use with cyclosporine and tacrolimus?

Answer 27

sirolimus

Question 28

what is the main therapeutic use of sirolimus?

Answer 28

renal transplant patients that cant tolerate calcineurin inhibitors due to high-risk nephrotoxicity

Question 29

what is the MOA of antithymocyte globulin?

Answer 29

1. antibodies that bind to CDs (especially CD3) and HLAs on T cells 2. depletion of circulating T cells via a) complement cytotoxicity and b) prevention of T cell activation

Question 30

what is the MOA of muromonab CD3?

Answer 30

anti-CD3 antibodies cause depletion of T cells

Question 31

what is the main therapeutic use of muromoab CD3?

Answer 31

reversal of glucocorticoid resistant organ transplant rejection episodes

Question 32

what is the main adverse reaction of muromonab CD3?

Answer 32

cytokine storm

Question 33

what is the MOA of the anti-TNFa reagents?

Answer 33

binds directly and prevents TNFa from binding to its receptors

Question 34

what are the anti-TNFa agents?

Answer 34

infliximab adalimumab etanercept

Question 35

what are the therapeutic uses of the anti-TNFa agents?

Answer 35

RA | IBD

Question 36

what class of drug is cyclosporine?

Answer 36

calcineurin inhibitor

Question 37

what class of drug is tacrolimus?

Answer 37

calcineurin inhibitor

Question 38

what class of drug is azathioprine?

Answer 38

antiproliferative / antimetabolite

Question 39

what class of drug is mycophenolate mofenil?

Answer 39

antiproliferative / antimetabolite

Question 40

what class of drug is sirolimus?

Answer 40

antiproliferative / antimetabolite

Question 41

what class of drug is antithymocyte globulin?

Answer 41

biologic

Question 42

what class of drug is muromonab-CD3?

Answer 42

biologic

Question 43

what class of drug is anti-TNFa?

Answer 43

biologic