Immunosuppressants Flashcards
cyclosporine moa
after diffusing into T cell ,binds to cyclophilin (immunophilin) to form a complex that binds to calcineurin.
calcineurin is resp for dephosphorylation of NFATc(cytosolic nuclear factor of activated T cell)
because the cyclosporine- calcineurin complex cannot perform this reaction , NFAT cannot enter nucleus to promote synthesis of cytokines including IL2
adverse effects of cyclosporine
NEPHROTOXICITY
hepatotoxicity infections lymphoma htn hyperlipidemia hyperkalemia tremor hirusitism glucose intolerance gum hyperplasia
moa of tacrolimus
same as cyclosporine but binds to different immunophilin FKBP12 (binding protein)
elimination of cyclosporine and tacrolimus via
feces
tacrolimus SE
MORE
nephrotoxicity
neurotoxicity(tremor , seizures , hallucination)
LESS
cvs-hyperlipidemia, htn
NO
gingival hyperplasia
hirusitism
hyperkalemia
costimulation blockers moa
blocks CD28 mediated costimulation of T lympho by binding to CD80 and 86 on APCs
belatacept
second generation costimulation blockers
iv maintainance immunosuppressant
drug interaction of calcineurin inh and mTOR inh
substrate of CYP3A4 and Pgp
everolimus/sicrolimus increase cyclosporine level leading to more nephrotoxicity so dose should be decreased
adr of sirolimus
main -hyperlipedemia
inc cyclosporine levels
rest not imp
adr of everolimus
same
additional- angioedema
moa of azathioprine
prodrug that is first converted to 6-MP which is converted to nucleotide.
so acts as a purine nucleotide analog
int of allopurinol and azathioprine
allopurinol inhibits metabolism of azathioprine so dose of azo should be reduced.
moa of mycophenolate mefetil
reversible non comp inhibitor of inosine monophosphate dehydrogenase which blocks de novo synthesis of guanine phosphate
(no salvage pathway in lympho)
SE of mycophenolate mofetil
git
n/v , diarrhoea, abdominal pain
moa of basiliximab
anti CD25 Ab that binds to the IL2 receptor on activated T cells and interfere with proliferation of these cells
