anticancer antimetabolites

Question 1

folate antagonist

Answer 1

methotrexate

Question 2

what does methotrexate do

Answer 2

interferes with thymidylate synthesis

inhibits dihydrofolate reductas

Question 3

how does it inhibit dihydrofolate reductase

Answer 3

normally it adds 2 hydrogens and then 2 others

to get folic acid to tetrahydrofolate

Question 4

when does this drug act

Answer 4

on S-phase

Question 5

solubility of methotrexate

Answer 5

low lipid solublility

does not cross bbb readily

Question 6

how is it taken up into cells

Answer 6

activity taken up into cells via folate transporter

Question 7

what is it metabolised to

Answer 7

polyglutamate derivatives

retained in cells for a few weeks

Question 8

how does resistance develop

Answer 8

decreased drug transport

increased expression of dHFR

Question 9

unwanted effects

Answer 9

depression of bone marrow
damage to epithilium of GI tracts
pneumonia

Question 10

10x dose used in methotrexate resisitance what does it cause

Answer 10

leads to nephrotoxicity

caused by precipitation of drug or a metabolite in renal tubes

Question 11

10x dose used in methotrexate resisitance effects can be rescued by

Answer 11

adding thymine in the clinical form of leucovorin

Question 12

leucovorin what is it used for

Answer 12

removes effecr of methotrexate before new haemopoietic cells in 60 are recruited into the cell cycle