Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
27 Cards in this Set
- Front
- Back
|
what gene inhibits apoptosis
|
FLIP
|
|
|
what is the MOA of alkylating agents
|
add bulky alkyl groups onto DNA and covalently crosslink within a strand or to both strands of DNA this limits cell growth and causes apoptosis
|
|
|
why are alkylating agents more damaging to cancer cells
|
cancer cells spend more time in S phase where the DNA is open and vulnerable
|
|
|
what must be given w/ Ifosfamide and why
|
MESNA must be given b/c the metabolite of ifosfamide (acrolein) is very toxic and may cause hemorrhagic cystitus but when MESNA is given it forms a thioether that is H2O soluble and not toxic
|
|
|
what is unique about the platinum alkylating agents
|
they don't add an alkyl group only crosslink
|
|
|
what are the ADR of alkylating agents
|
bone marrow suppression
damage mucosa, death/sloughing of epithelium lining GI tract N/V ulceration ALL CAUSE LUNG FIBROSIS |
|
|
what is the drug resistance to alkylating agents
|
insufficient intracellular levels of drug (export pumps)
increased cellular repair (prevents apoptosis) increased reducing agents/antioxidants (decrease damage) defect in apoptotic pathway |
|
|
how is thymylate made
|
dihydrofolate is converted to tetrahydrofolate which then donates a methyl group to the reaction b/t uridylic acid and thymidylate synthetase
|
|
|
what inhibits dihydrofolate reductase
|
methotrexate
pemetrexed |
|
|
how is MTX and Folinic acid taken up
|
MTX and Folinic acid are taken up via active transport and once inside they get polyglutaminated and become more water soluble and are trapped inside the cell
Folinic acid can also get endocytosed and once inside will get polyglutaminated |
|
|
how does inhibition of Dihydrofolate reductase impact the cell
|
it can no longer make tetrahydrofolate which is needed by a rapidly dividing cell in order to make thymidylate
|
|
|
what form of Leucovorin is active
|
L form
|
|
|
when must Leucovorin be given
|
48hrs post anti folate therapy
|
|
|
how does Leucovorin work
|
it is used to rescue our normal cells after treatment w/ agents that inhibit dihydrofolate reductase
|
|
|
what is the MOA of pemetrexed
|
inhibits dihydrofolate reductase
inhibits purine biosynthesis (GARTF, AICARTF) inhibits thymidylate synthetase INHIBITS DNA SYNTHESIS TO A GREATER EXTENT THAN MTX |
|
|
what is the resistance to Methotrexate and Pemetrexed
|
insufficient concentration (efflux pumps)
mutation in DHFR enzyme altering affinity DHFR gene amplification |
|
|
what fluoropyrimidine analog is also a cytidine analog
|
capecitabine
|
|
|
what is unique about cytosine arabinoside, 5 azacytidine, gemcitabine
|
cytosine arabinoside (2'OH is trans to 3'OH)
5 Azacytidine (has 3 N) Gemcitabine (has 2 F) |
|
|
how does 5-FU become active
|
once it enters the cell membrane thymidine phosphorylase adds a deoxyribose then it gets phosphorylated by thymidine kinase into the active form 5-dUMP
|
|
|
how does 5-FU work
|
once active it forms a complex with thymidylate synthetase making TS unable to make further thymidylate
also gets incorporated into DNA due to a lack of thymidine and results in apoptosis |
|
|
why is leucovorin used w/ 5-FU
|
to insure that the cancer cells have the 3rd component of the complex since cancer cells may be low on tetrahydrofolate due to constant cell division
|
|
|
what is the resistance mechanisms of 5-FU
|
increase thymidylate synthase
mutation in thymidylate synthase insuficient enzymes that convert 5-FU (TK, thymidine phosphorylase) |
|
|
how does Cytarabine work
|
competes w/ cytidine for DNA polymerase and causes an error leading to apoptosis
has 2'OH trans to 3'OH |
|
|
how does Capecitabine become a uracil
|
via cytosine deaminase
|
|
|
what resistance is ther ew/ cytarabine
|
mutation in AraC converting enzymes (cytidine kinase), excess cytidine deaminase converts it to Uracil
|
|
|
what is the MOA of 5-Azacytidine
|
incorporates into DNA/RNA and induces demethylation of methylated genes by inhibiting methyltranferase
|
|
|
what is the MOA of gemcitabine
|
competes w/ cytidine for DNA polymerase and causes chain termination (requires an additional base to be effective after chain termination)
inhibits ribonucleotide reductase therefore limits supply of deoxynucleotides (C, G,A,T) |
