Renal Pharm pt2 Flashcards
pharmacokinetics predisolone
action take >8hours
benefits of mTOR inhibitor sirolimus over calcineurin inhibitors Cyclosporine, tacrolimus
prophylaxis against cellular jrection
less vasoconstriction
no acute/chronic renal insuffciency
down regu of TGF-B+ PDGF > less interstial fibrosis
interleukin 2 receptor abx
daclizumab (95% human)
Basiliximab (75% human)
alemtuzmab (humanized)
drug interaction sirolimus
CYP3A4 inducers - Rifampin
CYP450 inhibitors - itraconazole, ketoconazole
___- may potentiate adverse events with calcineurin inhibitors
prednisolone
indications belatacept
renal transplant for patients seropos for ebstein Barr
indicated drug class in membranous nephropathy
ACEi, ARB
cotricosteroids, immunosuppresants
monitoring needed for mycophenolate mofetile
CBC to monitor hematologic side effects
GI side effects common when dose >1g bid > reduce dose
pharmacokinetics and side effects belatacept
long half life - 8-10-days
hypersensitivity
lymphoproliferative if no prior exposure to ebstein barr
pharmacokinetics taccrolimus
or or IV
more water soluble than cyclosporine
variable half -lfie
pharmacokinetics basiliximab
long half life (1 week)
given prior to surgery and 4 days following
3 path ot immunosuppression
Calcineurin
Mtor Pathway
Cell cycle pathway (antimetabolites)
calcineurin inhibitors
cyclosporine
tacrolimus
side effects cyclosporin
nephrotoxicity - vasoconstrition, induce TGFB, fibrosis+atrophy)
HTN+fluid retension
Hepatic dysfunction
tremor, headache, fatigue
Hypertrichosis (hair growth)
gum hypertrophy
hyperlipidemia, hyopmagnesmia, hypokalemia
pharmacokinetics mycophenolate mofetil
oral or IV
liver metab
long half-life - 18 hours
interaction with mycophenolate mofetil
Rifampin, phenobarbital, phenytoin
decrease MPA levels
interaction with mycophenolate mofetil
corticosteroids, cyclosporine
decrease MPA levels
indicated drug class in IgA nephropathy
ACEi
corticosteroids or immunosuppresents
indicated drug clase in focal segmental glomerulosclerosis
ACEi
corticosteroids, immunosuppresants
monitoring needed for azathioprine
complete blood count to monitor hematologic side effects
side effects sirolimus
Edema, ascities
tachycardia, HTN
hyperlipidemia, hypokalemia, hypophos
Rash
Lymphocele > can cause ereteric compression in transplant
mTOR inhibitor
sirolimus
death post kidney transplant causes
Infection
CVD
Malignancy
issue with antiacids in calcineurin inhibitors
mg and aluminum antiacids inhibit abs
should wait until 2hrs after calcineurin inhibitor dose
interaction with mycophenolate mofetil
antacids, cholstyramine, sevelamer, feso4
decrease MPA levels
indicated drug class in Neprhotic syndrome
ACEi, ARB
pharmacokinetics sirolimus
oral
abs modulated by p-glycoproteins
metabolized by CYP450
very long half life (60hours)
higher impact on lipid levels, cyclosporine or tacrolimus?
cyclosporine greater
risk of HMG-CoA reductase inhibitors (statins) with calcineurin inhibitors (Tacrolimus, cyclosporine)
increased risk of rhabdomyolysis
bone marrow suppression
costimulator Cd80 and Cd86 blocker
belatacept
side effects tacrolimus
pleual effusion
cardial effusion
cardiomyopathy in children
mechanism calcineurin inhibitors (Cyclosporine + tacrolimus)
bind to cyclphilin (cyclosporine) or FBKP12 (tacrolimus)
complex binds and inhibits calcineurin
inhibits transcription of Il-2 > inhibit Tcell activation and prolif
therapeutic action prednisolone
inhibit proinflam like NF-kB
activate anti-inflam genes via histone acetlyation
reduce T-cell prolif and increase Tcell apop
reduce Tcell activation, b-cell pro-lif
mechanism+metabolism azathioprine
methotrexate
cyclophosphamide
metabolized to 6mercaptopurine>TIMP in liver
TIMP decreases synthesis of DNA precursors
block CD28 costim of Tcells
pharmacokinetics Azathioprine
oral
short half life (3-5 hours)
metabolized to TIMP in liver
mechanism of aaction sirolimus
binds FKBP12 > mdoulates activity of mTOR
inhibits IL-2 induced cell progression from G1 to S phase
drug interactions azathioprine
allopurinol > decrease 6 mercaptopurine metabolism,
must reduce azathioprine dose by 75% if used together
antiproliferative antimetabolitte
mycopehnolate mofetil
side effects azathioprine
bonemarrow supression, leucopenia, thrombocytopenia
hypersensitivity reactions
opportunistic infection
alopecia
small risk of lymphomas
side effects mycophenolate mofetil
leucopenai, thrombocytopenia, anemia
HTN edema, tachycardia (electrolytes)
dypsnea, cough
opportunistic infections
lymphoproliferative disease
skin cancer
purine analogs antiproliferative agents
block CD28 co-stimulation of Tcells
Azothioprine
cyclophosphamide
methotrexate
drug interactions cyclosporing
nephrotoxic drugs - NSAIDs, aminoglycosides, antimicrobials
**CYP3A3 inducers - **phenytoin, carbamazepine
**CPY450 inhibitors **- erythromycin, ketoconazole
side effects basiliximab
hypersensitivity reactions
critical consideration with induction agents in kidney rejections
check fluid volume status
pharmocokinetics cyclosporine
or or IV
concentrates in liver, kidney, spleen, marrow
metabolized by CYP3A4 in liver
27 hour halflife
interaction with mycophenolate mofetil
tacrolimus, sirolimus
no change in MPA levels
induction agents to combat kidney transplant rejection
muronomab
anti-thymocyte globulin (deplete circulating lymphocytes)
daclizumab (IL-2 receptor)
basiliximab (IL-2 receptor)
alemtuzumab (IL-2 receptor)
FTY-720 - lymphocyte homing
side effects prednisolone
acne
cushings face
hirsutism
mood disorder
HTN, glucose intolerance
cataracts
osteoporosis
growth retardation
indicated drug class in lupus nepritis
class V corticosteroids
mechanism mycophenolate mofetil
competive/reversible inhibition of IMPDH > rate limiting de-novo purine synth
lymphocytes dependent on denove pathway > inhibits B and T lymphocyte prolif
