• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/41

Click to flip

41 Cards in this Set

  • Front
  • Back
methotrexate action
folic acid mimic that inhibits dihydrofolate reductase (DHFR). this enzyme produces THF, which is the methyle and methylene donor for thymidine and purine synthesis. prodrug must be activated via enzymatic addition of several glutamates.
methotrexate uses
IV or oral formulations. very versatile cancer treatment (breast, colorectal, lymphoma, etc.). high dose MTX performed with reduced folates (leucovorin rescue).
methotrexate toxicity
mucositis, kidney damage, hepatotoxicity
methotrexate resistance mechanisms
reduced uptake from carriers, decrease in enzymes that add polyglutamate, DHFR gene amplification
hydroxyurea action
inhibits ribonucleotide reductase, which reduces nucleotide triphosphates (NTPs) to dNTPs for DNA synth. complexes with active site non-heme iron.
hydroxyurea uses
leukemias, head and neck cancers
hydroxyurea resistance mechanisms
overexpression of reductase
hydroxyurea toxicity
"standard toxicities" (hair loss, neutropenia?)
5-fluorouracil (5-FU) action
active form (5-F-dUMP) covalently modifies thymidylate synthase, which converns dUMP to TMP. reduced TMP reduced thymidine pools for DNA synth. 5-FU activated by thymidine phosphorylase, thymidine kinase, and pyrimidine kinases. leucovorin cotreatment enhances 5-FU binding to TS.
5-fluorouracil (5-FU) uses
IV and oral formulations. colorectal and breast cancer, usually in combination with other drugs.
5-fluorouracil (5-FU) toxicity
bone marrow suppression
5-fluorouracil resistance mechanisms
decreased activity of activating enzymes. dihydropyrimidine dehydrogenase inactivates 5-FU. inhibition with 5-ethynyluracil moves 5-FU towards activated drug pathway.
ftorafur
oral prodrug of 5-FU
fluorodeoxyuridine
works just like 5-FU
5-FU + leucovorin action
leucovorin pushes thymidylate enzyme towards inactive adduct formation via l'chatelier's principle by acting as the covalently bound coenzyme.
methotrexate + leucovorin action
leucovorin is a highly bioavailable THF analog that rapidly replenishes THF to save rapidly dividing normal cells after cancer cells have been damaged beyond rescue.
6-thiopurine, 6-thioguanine action
activated to form mononucleotides that act as competitive inhibitors of enzymes for purine synthesis and get incorporated in DNA
azothioprine
prodrug for 6-mercaptopurine, which acts like 6-thioguanine
6-thiopurine, 6-thioguanine uses
oral administration for leukemias
6-thiopurine, 6-thioguanine toxicity
bone marrow suppression
6-thiopurine, 6-thioguanine resistance mechanisms
inactivated by xanthine oxidase. decrease in HGPRTase (activating enzyme).
cytosine arabinoside (cytarabine, Ara-C) action
cytidine analog inhibitor of DNA polymerase
gemcitabine action
cytidine analog inhibitor of DNA polymerase
fludarabine action
adenosine analog inhibitor of DNA polymerase
5-azacytidine (5-aza-C) action
cytidine analog inhibitor of DNA polymerase
2-chlorodeoxyadenosine (cladribine, 2-CdA) action
adenosine analog inhibitor of DNA polymerase
DNA polymerase inhibitor action
nucleoside analogs that are activated by deoxycytidylate kinase nucleoside diphosphate kinase. block DNA strand elongation.
gemcitabine uses
pancreatic cancer
cytarabine uses
acute myelogenous leukemia
fludarabine uses
chronic lymphocytic leukemia
DNA polymerase inhibitor toxicity
myelosuppression
DNA polymerase resistance mechanism
decreased activity of activating enzymes, decreased nucleoside transport, cytarabine inactivated by cytidine deaminase
imatinib (Gleevec) action
inhibitor of tyrosine kinases BCR-ABL, c-Kit TK, and PDGF-RK
imatinib (Gleevec) uses
treats hyperactive BCR-ABL in chronic myelogenous leukemia, c-KIT TK in gastrointestinal stromal tumors
protein kinase inhibitor resistance mechanisms
amplification of oncogenic protein kinase, mutations in kinase catalytic domain
trastuzumab action
humanized monoclonal antibody that binds to extracellular region of HER2
trastuzumab uses
treat 25% of breast cancers that exhibit HER2 overexpression
cetuximab action and use
anti-EGFR monoclonal antibody used for colorectal and head and neck cancers.
gefitinib action and use
EGFR tyrosine kinase inhibitor effective against non-small cell lunch cancer
bortezomib (Velcade) action
boronic acid dipeptide inhibitor that targets chymotrypsin-like active site of the proteasome.
bortezomib (Velcade) uses
used against myeloma