immunosuppressants Flashcards
cyclosporine inhibits
calcineurin
tacrolimus inhibits
calcineurin
calcineurin activates
NFAT (which is an imp transcription factor for many cytokines)
cyclosporine binds to
cyclophilins which inhibits calcineurin
tacrolimus binds to
FK-506 binding protein which inhibits calcineurin
cyclosporine is metabolized by
P450
tacrolimus is metabolized by
P450
side effects of cyclosporine
nephrotoxicity (vasoconstriction of afferent/efferent arterioles
HTN
tacrolimus side effects
nephrotoxicity (vasoconstriction of afferent/efferent arterioles
HTN
cyclosporine can also cause
hyperuricemia
hyperglycermia
neurotoxicity
two unique side effects of cyclosporine
- gingival hyperplasia
- hirsutism
tacrolimus can also cause
hyperuricemia
hyperglycermia
neurotoxicity
sirolimus moa
inhibits mTOR by binding FK binding protein
sirolimus block response to
IL-2 in B/T cells
sirolimus (rapamycin) side effects
anemia
thrombocytopenia
hyperlipidemia
hyperglycemia
coronary stents (drug eluting stents) coated with
anti-proliferative drug that blunts scar tissue growth
methotrexate moa
mimics folic acid and inhibits dihydrofolate reductase
methotrexate side effects
myelosuppression
stomatitis/mucosisits (mouth soreness)
myelosuppression with methotrexate is reversible with
leucovorin
mycopheolic acid inhibits
IMP dehydrogenase causing decreased DNA synthesis
IMP dehydrogenase is rate limiting step in
purine synthesis in lymphocytes
side effects of mycopheolic acid
N/V, cramping, abd pain
cyclophosphamide powerful immunosuppressant used in
vasculitis, glomerulonephritis
cyclophosphamide requires
bio activation by liver
cyclphosphamide is a
alkylating agents (adds alkyl group to N7 position of DNA)
cyclophosphamide ultimately causes DNA to cross link causing
inhibition of DNA replication
side effects of cyclophosphamide
myelosuppression
hemorrhagic cystitis
cyclophosphamide toxic metabolite
acrolein
cyclophosphamide can also cause
SIADH
SIADH leads to
hyponatremia and possible seizures
azathioprine is a prodrug converted to
6-mercaptopurine
6-MP competes for binding to
hypoxanthine guanine phosphoribzosyltransferase (HGPRT)
HGPRT is important for
synthesis of new purine nucleotides
azathioprine side effects
anorexia, N/V, bone marrow suppression
caution using azathioprine with
allopurinol (blunts metabolism of 6-MP)
muromonab-CD3 is a
monoclonal antibody used in organ transplant
muromonab-CD3 binds to
CD3 (T cells) and block activation
muromonab-CD3 leads to
T cell depletion from circulation
key side effect of muromonab-CD3
cytokine release syndrome
infliximab is an antibody against
TNF alpha
infliximab is used in
RA, crohns
infliximab is
chimeric (both mouse and human components)
risk of infliximab
reactivation of TB
etanercept
decoy receptor for TNF alpha
malaria drugs
chloroquine & hydroxychloroquine
chloroquine & hydroxychloroquine block
TLR in B cells and increase pH (causing decreased activity)
