37. Immunosuppressants Flashcards Preview

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Flashcards in 37. Immunosuppressants Deck (47):
1

mechanism of action

agents that block lymphocyte activation and proliferation

2

immunosu[[resants reduce acute transplant immunity by suppresing

cellular immunity

3

immunosuppresants- frequently combined to

achieve greater efficasy with decrease toxicity

4

Immunosuppresants - chronic suppresion high risk for

1. infenction
2. Malignancy

5

Immunosuppressants - drugs

1. cyclosporine
2. Tacrolimus
3. Sirolimus (Rapamycin)
4. Daclizumab
5. Basiliximab
6. Azathioprine
7. Mycophenolate modetil
8. Corticosteroids

6

Cyclosporine - mechanism of action

1binds cyclophilin --> the complex inhibits calcineurin ( a TCR downstram protein that activates NFAT, a TF through dephosporylation) --> Prevent IL-2 transcription
--> blocks T cell activation

7

cyclosporine - clinical use

1.transplant rejection prophylaxis
2. psoriasis
3. RA

8

Cyclosporine- toxicity

1. nephrotoxicity
2. hypertension
3. hyperlipidemia
4. neurotoxicity
5. gingival hyperplasia
6.hirsutism

9

Tacrolimus - mechanism of action

binds FK506 --> the complex inhibits calcineurin ( a TCR downstram protein that activates NFAT, a TF through dephosporylation) --> Prevent IL-2 transcription
--> blocks T cell activation

10

Tacrolimus - clinical use

transplant rejection prophylaxis

11

Tacrolimus -side effects

1.Diabetes
2.Nephrotoxic
3.Neurotoxicity
4.Hypertension

12

Tacrolimus and cyclosporine are both highly ... (side effect)

nephrotoxic

13

Sirolimus (Rapamycin) - mechanism of action

binds FKB --> the complex inhibits mTOR ( IL-2R downstream) --> blocks T-cell activation and B-cell differentiation by preventing RESPONSE TO IL-2

14

Sirolimus (Rapamycin)- clinical use

1. kidney transplant rejection prophylaxis
2. also used in drug-elunting

15

A drug eluting stent (DES) is a

peripheral or conorary stent placed into narrowed peripheral or coronary arteries --> slowly releases a drug to block cell proliferation---> prevents fibrosis + clots --> prevent restenosis

16

Sirolimus (Rapamycin) - side effects

1. Pancytopenia
2. Insulin resistance
3. Hyperlipidemia
NOT NEPHROTOXIC

17

Sirolimus (rapamycin) is no (toxicity

Nephrotoxic

18

Sirolimus (Rapamycin ) act synergic with

cyclosporine

19

Daclizumab - mechanism of action

monoclonal antibody that blocks IL-2R

20

Basiliximab - mechanism of action

monoclonal antibody that blocks IL-2R

21

Daclizumab, Basiliximab - clinical use

kidney transplant rejection

22

Daclizumab, Basiliximab -

1.Edema
2.Hypertension
3.tremor

23

Azathioprinw -mechanism of action

Antimetabolite prexurson of 6-MP--> inhibit PRPP amidotransferase --> decrease de novo purine synthesis --> inhibits lymphocyte proliferation

24

Azathioprine toxicity

1. Myelosuppresiion
2. GI toxicity
3. Liver toxicity

25

Azathioprin and MP- metabolized by

Xanthine oxidase

26

Azathioprine- clinical use

1.Transplant rejection prophylaxis
2.RA
I3.IBD
4.Glomerulonephritis
5. Other autoimmun conditions

27

Mycophenolate mofetil - mechanism of action

Reversibly inhibits IMP dehydrogenase preventing purine synthesi of B and T cells

28

Mycophenolate mofetil - clinical use

1. Transplant rejection
2. Lupus nephritis

29

Mycophenolate mofetil - toxicity

1. Gi upset
2. Pancytopenia
3. Hypertension
4. Hyperglycemia
5. Associated with invasive CMV infection

LESS nephrotoxic and neurotoxic

30

Corticosteroids as immunosuppressants - mechanism of action

Inhibir NF-KB --> supress both B and T call function by decreased transcription of many cytokines
2. induce apoptosis of t-lymphoxytes

31

Corticosteroids clinical use

1. transplant rejection prophylaxis
2. manu autoimmune disordes
3. inflammantory disordes

32

Corticosteroids toxicity

hyperglycemia, osteoporosis , central obesity, muscle breakdown, psychosis, acne, hypertension, cataractts, avascular necrosis (femoral head)

33

• What are the clinical uses of cyclosporine?

Minimization of organ rejection after transplantation (prophylaxis) and treatment of autoimmune disorders (psoriasis, rheumatoid arthritis)

34

Tacrolimus works by binding to the ___-binding protein to inhibit ___ transcription.

FK506 (also known as FKBP), interleukin 2

35

A patient takes a drug to prevent transplant rejection. She develops gingival hyperplasia and hirsutism. Is she taking tacrolimus?

No, as tacrolimus does not cause gingival hyperplasia or hirsutism (she is likely taking cyclosporine)

36

A diabetic patient with diabetic neuropathy receives a kidney transplant. Do you prescribe cyclosporine or tacrolimus for immunosuppression?

Cyclosporine, as tacrolimus is associated with an increased risk of both diabetes and neurotoxicity, making it a poor choice in this patient

37

A man with a kidney transplant is taking sirolimus to prevent rejection. What is the mechanism? What effect does this have on immunity?

Sirolimus (rapamycin) inhibits mammalian target of Rapamycin (mTOR) and FKBP; blocks IL-2 signal transduction and thus B-/T-cell activity

38

A patient receives a kidney transplant. What drugs can be used together to prevent transplant rejection and lower toxicity?

Cyclosporine and sirolimus (rapamycin) (unlike cyclosporine, sirolimus is not nephrotoxic [the kidney "sir-vives"])

39

A man with a kidney transplant is taking sirolimus (rapamycin). What three toxicities do you warn him about?

Blood count abnormalities (anemia, thrombocytopenia, leukopenia), insulin resistance, and hyperlipidemia

40

Azathioprine is a precursor for which metabolite? How does this metabolite reduce immune system function?

Azathioprine is a precursor to 6-mercaptopurine; it interferes with nucleic acid synthesis (toxic to proliferating lymphocytes)

41

A man is taking azathioprine. What are the clinical indications for its use?

Immunosuppression during transplantations and for autoimmune disorders such as rheumatoid arthritis, glomerulonephritis, Crohn disease

42

A man taking allopurinol for gout starts an immunosuppressive agent for Crohn disease. Pancytopenia develops rapidly. What happened?

Azathioprine's metabolite, 6-MP, is metabolized by xanthine oxidase, & allopurinol inhibits xanthine oxidase, causing toxic levels of 6-MP

43

A man with a recent kidney transplant takes basiliximab. How does it work? What toxicities should you warn him about?

Monoclonal antibody blocks the interleukin 2 receptor; side effects (toxicities) include tremor, edema, hypertension

44

A liver transplant patient develops hyperglycemia, central obesity, and acne. What drug class may cause such symptoms? What syndrome is this?


Glucocorticoids; iatrogenic Cushing syndrome

45

• A patient takes glucocorticoids for autoimmune hemolytic anemia. What are some side effects you should warn the patient about?


Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, hypertension, cataracts, avascular necrosis

46

• A woman with coronary artery disease receives a drug-eluting stent with an immunosuppressive agent. Is nephrotoxicity a concern?

No, as the agent being eluted from the stent is likely sirolimus, which is not nephrotoxic

47

• What two monoclonal antibodies, used for transplant rejection prophylaxis, work by blocking IL-2R?

Daclizumab and basiliximab