Immunosuppression

Question 1

What are the main uses of immunosuppressants?

Answer 1

Organ transplant

Autoimmune diseases

Question 2

What is a general side effect of all immunosuppressants?n

Answer 2

Infections

Question 3

Does prednisone have a specific target?

Answer 3

No, it does general suppression, not specific to anything

Question 4

What is the main side effect of short term prednisone use?

Answer 4

Hyperglycemia

Question 5

What are the side effects of long term use of prednisone?

Answer 5

Buffalo hump

Increased abdominal fat

Osteoporosis

Weight gain

Menstrual/reproductive issues

Question 6

What two classes of drugs might give you a buffalo hump and truncal obesity?

Answer 6

Protease inhibitors

Corticosteroids

Question 7

What are the two types of T-cell suppressants and which drugs are in each type?

Answer 7

Calcineurin Inhibitors:

• cyclosporine
• tacrolimus

Proliferation Signal Inhibitors:
-sirolimus

Question 8

What are T-cell suppressants used for most often?

Answer 8

Preventing rejection

Question 9

Are T-cell suppressants selective, or do they have widespread effects?

Answer 9

Selective for T-lymphocytes, leaving the rest of the immune system intact with no bone marrow suppression

Question 10

Will cyclosporine suppress bone marrow?

Answer 10

No.

B cells still around to help fight infection

Question 11

How does cyclosporine work?

Answer 11

inhibits calcineurin/T-cell activation and preventing the release of IL-1 and IL-2

Question 12

Are there any drug interactions with cyclosporine?

Answer 12

Yes, many.

Rifampin will induce 3A4, and decrease cyclosporine concentration

Erythromycin and ketoconazole will inhibit 3A4 and increase cyclosporine concentration

Question 13

Let’s say you have a TB patient taking rifampin and now they have to start taking cyclosporine, what will happen to cyclosporine levels and what should you do about it?

Answer 13

Rifampin will induce 3A4 and decrease cyclopsporine levels.

Replace rifampin with rifabutin

Question 14

What are the main toxicities of cyclosporine?

Answer 14

Drug interactions

RENAL TOXICITY

Gingival hyperplasia

Hypertension

CNS- tremors, seizures, hallucinations

Question 15

You just got a kidney transplant and your doctor wants to start you on cyclosporine to prevent rejection. What should you do?

Answer 15

Run away because cyclosporine is extremely damaging to kidneys

Question 16

You just got a transplant and your gums are starting to look a little wild. They’re big and puffy and really unsightly. You might just be hallucinating, but you’re pretty sure your gums are jacked. What drug are you probably taking for anti rejection?

Answer 16

Cyclosporine

Question 17

What are the main side effects of tacrolimus?

Answer 17

Nephrotoxicity

Hypertension

Hyperglycemia, espeically with prednisone

Tremors

Headaches

Insomnia

(All pretty similar to cyclosporine, except for hyperglycemia, but this is less toxic than cyclosporine)

Question 18

You got a kidney transplant and you really need to be on a T-cell suppressant. Cyclosporine and tacrolimus are way too damaging to kidneys, so what should you take?

Answer 18

Sirolimus

Question 19

Does sirolimus target ONLY T-cells?

Answer 19

No. It is mostly T-cells, but there is some inhibition of B-cell differentiation

Question 20

What is the MOA of sirolimus?

Answer 20

Inhibits proliferation of T cells by binding to mTOR.

T cell cycle arrest and inhibition of B cell differentiation

Question 21

What kind of drug is mycophenolate (mofetil)?

Answer 21

Antiproliferative

Question 22

What is the MOA of mycophenolate-mofetil?

Answer 22

Inhibits purine synthesis in B and T cells

Inhibits inosine monophosphate dehydrogenase which is needed for purine synthesis in B cells AND T cells

Question 23

Does mycophenolate (mofetil) target only B cells or T cells?

Answer 23

Affects both

Inhibits the enzyme needed for purine synthesis

Question 24

What does azathioprine get metabolized into?

Answer 24

6-mercaptopurin

Question 25

What are the cytotoxic agents used for immunosuppression?

Answer 25

Azathioprine

Methotrexate

Cyclophosphamide

Question 26

Oh no, I’ve just been diagnosed with gout but i also take azathioprine for my lupus! Should i take some allopurinol?

Answer 26

No way because allopurinol inhibits xanthine oxidase, which is the same enzyme that metabolizes azathioprine. You could die from blood discrasias ☠️

Question 27

I take azathioprine everyday for my Crohn’s disease, and I’m ready to become a mom. Can i get pregnant

Answer 27

No, it is extremely teratogenic.

Find something else for your immunisuppresion, because the rest of them are not teratogenic

Question 28

What are the 2 types of biologics and which drugs are in each type?

Answer 28

Antibody Immunosuppressives:
Basiliximab (Simulect)
Adalimumab (Humira)
Abatacept (Orencia)
Etanercept (Enbrel)

Hematopoietic-stimulating Drugs:
G-CSF (neupogen)
Erythropoietin (epogen)

Question 29

What is the MOA of basiliximab?

Answer 29

Inhibits IL-2

Binds to IL-2 receptor and prevents it from being activated. IL-2 is responsible for a LOT of the immune response, so this is going to inhibit many parts of the immune pathway

Question 30

What are humira, enbrel, and orencia used for?

Answer 30

Psoriasis and RA

Question 31

What is the MOA of orencia?

Answer 31

Mimics CTLA4 and inhibits T-cell activation

Question 32

What is the MOA of humira and enbrel?

Answer 32

Humira is an antibody and Enbrel is a fusion protein, and they neutralize the activity of TNF-alpha

Question 33

What can we use for patients who have been on immunosuppressants or chemo drugs and they are now Anemic?

Answer 33

Epogen (Epoetin-alfa)

Same thing as EPO

Question 34

What can we do for our poor patient who has been on chemo and is now neutropenic?

Answer 34

Neupogen

Drives production of neutrophils