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Exam 1
Lecutre 5-antifolates
43
Agriculture
4th Grade
01/26/2014

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Term
antifolates are what kind of class
Definition
cell cycle specific
Term
specificity for cell phases means max effect on _ phase and none on-
Definition
S
G0
Term
advtg of cell cycle specific drugs-3
Definition
inhibiton of DNA/RNA at clincal dose
plateua cell sruvial wiht increase dose
minimal leukogeneisis/carincogenesis
Term
disadvtg of cell pahse specific drugs-2
Definition
fewer targets
little effect on slow grow/stem cells
Term
what are the antimetabolits of the CCS group-3
Definition
antifolates
purines
pyrimidines
Term
Foles
Definition
Methotrexate
Term
antimetabolites work bc they are struct similar to-
Definition
DNA/RNA synth intermediates
Term
antimetabolites affect _ synth, and tumor cells are more suscpetible bc
Definition
nucleic acid
they are dividing more
Term
folic acid is which vitamin
Definition
B9, folacin
Term
folic acid is used in what base conversion
Definition
uracil to thymine
Term
folic acid is struct similar to
Definition
MTX, aminopterin
Term
MTX and aminopterin inhibit
Definition
dihydrofolate reductase
Term
what does methotrexate inhibit-3
Definition
purine synth (RNA/DNA)
thymidine (tMP) synth
methionine, serine, f-met (proteins_
Term
MTX binds to- so it inhibits synth of
Definition
DHFR
Tetrahydrofolate
Term
cancers not sensitive to MTX-3
Definition
acute myelo leukemia
colon
renal
Term
cancers sensitive to MTX-4
Definition
acute lymph leukemia
nurkitts
choriocarcin
diffuse lympohma
Term
cytotoxic effect of MTX is mediated by-
Definition
polyglutamate form
Term
what metab MTX into cytotoxic form
Definition
folypolygutamyl synthetase
Term
polyglutamation is _ depenednet (2)
it occurs in tumor and less in nromal cells
Definition
time and conc
Term
the MTX ->plyglut probbaly account for selective activity of the drug as this is 80% in tumors
Definition
Term
MTX eliminated primary in
Definition
renal
Term
Admin for MTX-4
Definition
IM, oral, IV, intrathecal
Term
IT MTX prepared with-
Definition
preservative free NS
Term
when giving dose of MTX >1000, pt needs to:3
Definition
hydrate
void with specific grav <1.01
alkaline urin Ph> 7.5
Term
nephortox of MTX increases with UO<100 and pH<6.5*
Definition
Term
counseling for MTX and NSAID within 36 hrs: -3
Definition
will cause renal, meylo suppres, mucositis
Term
what drug slow MTX elmin and prolongs leucovorin-3
Definition
ASA, penicillins, sulfa
Term
ADEs of MTX-4
what is a reversible on?
Definition
stomatitis
nepho, headache, meylo
hepatox
Term
MTX plasma levels monitored until <0.05 and kidney funct why?
Definition
bc PK have high variability
Term
systemic tox of MTX correlates with
Definition
serum conc
Term
Leucovorin rescue dose adjusted to-
when is it stoppedd?
Definition
MTX level
MTX <.1
Term
time after dose MTX:
24 hrs, desired level?
48?
72?
Definition
<20
<1.0
<0.1
Term
resistance methods for MTX-4
Definition
transport
DHFR expression
altered DHFR
polyglut sythn
Term
DHFR amplificaiton is common tumor resistance *
Definition
Term
toxicity of MTX can be reversed by admin- how?
Definition
reduced folate
doesnt need DHFR activation
Term
leuvocorin is converted to _ which bypasses the inhibited MTX reductase
Definition
N5,N10 methylene FH4
Term
Leuvocorin is used when-
how mnay hrs afterr MTX dose?
Definition
MTX dose exceed 10-100 x conventional dose
24-36 hr
Term
luc=vocorin provides:3
Definition
able to use high MTX dose
reduced toxic effects
folate cofactors
Term
what is the multi target antifolate drug?
what are its 3 enzymes it inhibits?
Definition
pemetrexed
thymidylate synthase
dihydrofolate reductase
GARFT (glycin ribo formyltransferase)
Term
pemetrexed prevents formaiton of
Definition
DNA and RNA
Term
pemetrexed indications-2
Definition
mesothelioma
non small cell lung cancer
Term
toxicity most common wiht antimetab-3
Definition
nausea, mucositis, myelosupp
Term
toxicty with chronic methotrexate
tox with high dose methotex
Definition
hepatic
nephro
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