Antimetabolites--Fitz Flashcards
This is the folate replacement you give when using methotrexate
leucovorin
“leucovorin rescue”
Mechanism of leucovorin
folate substitute
uses reduced folate transporter to enter cell
normal cells express reduced folate transporter
cancer cells only express folate receptor
leucovorin therefore preferentially delivers “folate” to normal cells, allowing higher therapeutic levels of methotrexate to be reached
What is the syllable that indicates that a drug targets the folate pathway?
“trex”
How is leucovorin different from folate?
does not require activation by DHFR
Which 2 enzymes does methotrexate preferentially inhibit?
DHFR
TS (thymidylate synthase)
Why is methotrexate given IV?
allows to cross BBB
What supplement fluid is given with methotrexate?
bicarb
promotes renal excretion
How does 5-FU affect DNA synthesis?
inhibits thymidylate synthase
Capectiabine mechanism
activated to 5-FU in cells
Why is it a big deal that 5-FU is metabolized by dihydropyrimidine dehydrogenase?
8% of UK descendents are deficient in this enzyme
can be screened for
Why can’t you give 5-FU PO?
dihydropyrimidine dehydorgenase is found in the gut
==> intestinal metabolism before reaching target
6-mercaptopurin and 6-thioguanine mechansim
block guanylyl kinase
after activation by salvage pathway
What is the enzyme that activates 5-FU?
pyrimidine monophosphate
Function of dihydropyrimidine dehydrogenase?
metabolizes 5-FU
*some people are genetically deficiency
Function of thymidine phosphorylase
converts capecitabine to 5-FU
