Immunosuppressants Flashcards
What is the MOA for Glucocorticoids?
they bind to the Glucocorticoid receptor and the glucocorticoid response element (GRE) and regulates transcription
This leads to decreased circulating lymphocyte levels and suppresses some subsets of T cells and antigen stimulation of T cell proliferation (T-cell production, IL2 production) and inhibits the function of phagocytes
what is the clinical use for glucocorticoids?
prevent rejection (prophylaxix)
at high doses you can treat acute rejection episodes
GVHD
and autoimmune diseases (acute glomerular nephritis, autoimmune hemolitic anemia)
Glucocorticoids
Adverse Effects
Endo: decreased hormone release
eye: glaucoma/cataracts
moon facies
buffalo hump
easy bruising
poor wound healing
Muscle wasting
renal system (fluid retention, electrolyte imbalances)
reduced fertility
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One of the most serious adverse effects of glucocorticoid use:
Osteoperosis
d/t increased bone resorption and decreased bone formation
decreased calcium absorption from gut
Names of Glucocorticoids
Prednisone
Methylprednisolone
Calcineurin inhibitors
MOA
Calcineurin inhibitors
decrease IL-2 transcription
Cyclosporine binds to cyclophillin
Tacrolimus binds to FKBP.
NFAT-P isn’t dephosphorylated which is required for interleukin synthesis
Calcineurin inhibitors
route of administration
metabolism
IV or oral
CYP450 3A
Calcineurin inhibitors
Clinical Usage
Calcineurin inhibitors
allograft transplantation (not effective in ongoing or acute rejection)
GVHD (used in combination with Methotrexate)
Psoriasis
RA
Calcineurin inhibitors
Black Box Warning
Calcineurin inhibitors
Skin cancer
increased risk of infection
nephrotoxicity
Calcineurin inhibitors
what causes acute nephrotoxicity?
Calcineurin inhibitors cause acute nephrotoxicity thru vasoconstriction of afferent and efferent glomerular arterioles
the amount of vasoconstriction is dose related and usually reversible
Calcineurin inhibitors
names
Calcineurin inhibitors:
Cyclosporine
Tacrolimus
What are the cardiologic effects of Calcineurin inhibitors?
What effect does it have on K+?
Calcineurin inhibitors cause a moderate increase in
BP.
Calcineurin inhibitors can cause hyperkalemia because of the reduced efficiency of urinary K+ secretion. Can be life threatening with concurrent administration of an ACEi
Sirolimus
Black Box
Sirolimus
Liver and lung transplants
can also cause hypokalemia, thrmbocytopenia, anemia, leukopenia, GI effects, edema, hypertension
Sirolimus
Metabolism
Half-Life
Sirolimus
CYP450 3A and P-glycoprotein
(use caution if coadministered with cyclosporine and tacrolimus)
60 hours
Sirolimus
MOA
Sirolimus
suppresses cytokine mediated T-Cell proliferation.
Binds to FKBP and forms a complex. This complex binds and blocks mTOR.
Azathioprine
MOA
Azathioprine
inhibits DNA synthesis during the S phase
azathioprine is converted to 6-MP which decreases the purine nucleotide pool which is needed for DNA replication (required in general but especially after antigen stimulation)