Immunosuppression Flashcards
What are the main uses of immunosuppressants?
Organ transplant
Autoimmune diseases
What is a general side effect of all immunosuppressants?n
Infections
Does prednisone have a specific target?
No, it does general suppression, not specific to anything
What is the main side effect of short term prednisone use?
Hyperglycemia
What are the side effects of long term use of prednisone?
Buffalo hump
Increased abdominal fat
Osteoporosis
Weight gain
Menstrual/reproductive issues
What two classes of drugs might give you a buffalo hump and truncal obesity?
Protease inhibitors
Corticosteroids
What are the two types of T-cell suppressants and which drugs are in each type?
Calcineurin Inhibitors:
- cyclosporine
- tacrolimus
Proliferation Signal Inhibitors:
-sirolimus
What are T-cell suppressants used for most often?
Preventing rejection
Are T-cell suppressants selective, or do they have widespread effects?
Selective for T-lymphocytes, leaving the rest of the immune system intact with no bone marrow suppression
Will cyclosporine suppress bone marrow?
No.
B cells still around to help fight infection
How does cyclosporine work?
inhibits calcineurin/T-cell activation and preventing the release of IL-1 and IL-2
Are there any drug interactions with cyclosporine?
Yes, many.
Rifampin will induce 3A4, and decrease cyclosporine concentration
Erythromycin and ketoconazole will inhibit 3A4 and increase cyclosporine concentration
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?
Rifampin will induce 3A4 and decrease cyclopsporine levels.
Replace rifampin with rifabutin
What are the main toxicities of cyclosporine?
Drug interactions
RENAL TOXICITY
Gingival hyperplasia
Hypertension
CNS- tremors, seizures, hallucinations
You just got a kidney transplant and your doctor wants to start you on cyclosporine to prevent rejection. What should you do?
Run away because cyclosporine is extremely damaging to kidneys
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?
Cyclosporine
What are the main side effects of tacrolimus?
Nephrotoxicity
Hypertension
Hyperglycemia, espeically with prednisone
Tremors
Headaches
Insomnia
(All pretty similar to cyclosporine, except for hyperglycemia, but this is less toxic than cyclosporine)
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?
Sirolimus
Does sirolimus target ONLY T-cells?
No. It is mostly T-cells, but there is some inhibition of B-cell differentiation
What is the MOA of sirolimus?
Inhibits proliferation of T cells by binding to mTOR.
T cell cycle arrest and inhibition of B cell differentiation
What kind of drug is mycophenolate (mofetil)?
Antiproliferative
What is the MOA of mycophenolate-mofetil?
Inhibits purine synthesis in B and T cells
Inhibits inosine monophosphate dehydrogenase which is needed for purine synthesis in B cells AND T cells
Does mycophenolate (mofetil) target only B cells or T cells?
Affects both
Inhibits the enzyme needed for purine synthesis
What does azathioprine get metabolized into?
6-mercaptopurin
What are the cytotoxic agents used for immunosuppression?
Azathioprine
Methotrexate
Cyclophosphamide
Oh no, I’ve just been diagnosed with gout but i also take azathioprine for my lupus! Should i take some allopurinol?
No way because allopurinol inhibits xanthine oxidase, which is the same enzyme that metabolizes azathioprine. You could die from blood discrasias ☠️
I take azathioprine everyday for my Crohn’s disease, and I’m ready to become a mom. Can i get pregnant
No, it is extremely teratogenic.
Find something else for your immunisuppresion, because the rest of them are not teratogenic
What are the 2 types of biologics and which drugs are in each type?
Antibody Immunosuppressives: Basiliximab (Simulect) Adalimumab (Humira) Abatacept (Orencia) Etanercept (Enbrel)
Hematopoietic-stimulating Drugs:
G-CSF (neupogen)
Erythropoietin (epogen)
What is the MOA of basiliximab?
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
What are humira, enbrel, and orencia used for?
Psoriasis and RA
What is the MOA of orencia?
Mimics CTLA4 and inhibits T-cell activation
What is the MOA of humira and enbrel?
Humira is an antibody and Enbrel is a fusion protein, and they neutralize the activity of TNF-alpha
What can we use for patients who have been on immunosuppressants or chemo drugs and they are now Anemic?
Epogen (Epoetin-alfa)
Same thing as EPO
What can we do for our poor patient who has been on chemo and is now neutropenic?
Neupogen
Drives production of neutrophils
