Chemotherapy MOAs Flashcards
Name 6 alkylating agents
Mustargen (aka mechlorethamine)
Melphalan
Cyclophosphamide (aka Cytoxan)
Chlorambucil
Lomustine (aka CCNU)
Procarbazine
At what point in the cell cycle do alkylating agents work best?
They are cell cycle phase nonspecific
What drug class includes mustargen, melphalan, cyclophosphamide, and chlorambucil?
Nitrogen mustards
Name two anti-tumor antibiotics
doxorubicin and mitoxantrone
How are mitoxantrone and doxorubicin related?
Mitoxantrone is a synthetic analog of doxorubicin
Name 4 anti-metabolite chemotherapeutics
Cytosine Arabinoside (aka Cytarabine, brand name Cytosar-U)
Methotrexate
Gemcitabine
Rabacfosadine (brand name Tanovea)
At what point in the cell cycle do anti-metabolite chemotherapeutics work best?
S phase
What drug class includes vincristine, vinblastine, vinorelbine, and vindesine?
Vinca alkaloids
What group of chemotherapeutics describes the vinca alkaloids?
anti-microtubule agents
At what point in the cell cycle do platinum anti-cancer agents work best?
S phase
What is the drug classification for Palladia?
tyrosine kinase inhibitor
What is the generic name for Palladia?
Toceranib phosphate
What is the brand name for Toceranib phosphate?
Palladia
What is the brand name for Rabacfosadine?
Tanovea
What is the generic name for Tanovea?
Rabacfosadine
What is the MOA of mustargen?
Hydrolyzes to nucleophilic reactive centers capable of forming DNA crosslinks. Interferes with DNA replication, RNA transcription, and protein synthesis
What is the MOA of Melphalan?
Bifunctional alkylating agent that interferes with RNA transcription and DNA replication, thereby disrupting nucleic acid function. Does not require activation by the liver. Actively transported into tumor cells by amino acid transporters
What is the MOA of cyclophosphamide?
Prodrug is metabolized and the metabolite enters cells and rapidly decomposes into alkylating agents that interfere with DNA replication and RNA transcription and replication to ultimately disrupt nucleic acid function
What is the MOA of Chlorambucil?
Enters cells through passive diffusion. Primary cytotoxic effect is due to alkylation of cancer cell DNA strands resulting in cross-linking and cellular apoptosis
What is the MOA of Lomustine?
MOA not completely understood; believed to inhibit DNA, RNA, and protein synthesis through alkylation and carbamoylation. Enters cells through passive diffusion.
What is the MOA of procarbazine?
Prodrug. precise MOA is not well understood, but it is considered to be an alkylating agent, and it appears to inhibit protein, RNA, and DNA synthesis. Procarbazine is auto-oxidized into hydrogen peroxide, which may also directly damage DNA
What is the MOA of Doxorubicin?
Inhibits DNA synthesis, DNA-dependent RNA synthesis, and protein synthesis by inhibiting DNA and RNA polymerases and impairing topoisomerase II, as well as through generation of free radicals. Doxorubicin alters transcription and replication by intercalating with DNA base pairs
What is the MOA of mitoxantrone?
Synthetic doxorubicin analog. DNA-reactive agent that binds in between DNA base pairs, causing crosslinks and strand breaks. Also interferes with RNA synthesis and is a potent topoisomerase II inhibitor. Does NOT cause oxidative destruction to cell and has reduced potential to produce ROS
What is the MOA of Cytarabine?
converted intracellularly into aracytidine triphosphate, which competes with deoxycytidine triphosphate to inhibit DNA polymerase, resulting in inhibition of DNA synthesis. Enters cells via active transport
What is the MOA for methotrexate?
inhibits folic acid reductase, preventing the reduction of dihydrofolate to tetrahydrofolate and affecting the production of purines and pyrimidines. Enters cells via active transport
What is the MOA for gemcitabine?
Metabolized intracellularly into a diphosphate and triphosphate form. The diphosphate inhibits ribonucleotide reductase. The triphosphate competes with dTCP (the “normal nucleotide”) for incorporation into DNA strands. DNA polymerase epsilon is unable to recognize the abnormal nucleotide (gemcitabine) and repair the DNA strand. Enters cells via active transport
What is the MOA for Tanovea?
Guanine nucleotide analogue. The pro-drug is processed by the body and in it’s active form, the drug is a potent, chain-terminating inhibitor of the major DNA polymerases, causing inhibition of DNA synthesis and resulting in S phase arrest
What is the MOA for Vinblastine/Vicristine?
Binds to β-tubulin to block microtubule formation and prevent mitotic spindle formation. Some can bind and dismantle formed tubules. Also interferes with amino acid metabolism by inhibiting glutamic acid utilization and preventing purine synthesis, citric acid cycle, and urea formation
What is the MOA for carboplatin/cisplatin?
Causes intra- and interstrand DNA cross-linking that causes single- and double-stranded DNA breakage, impairs DNA replication, RNA transcription, and protein synthesis, leading to cell death and inhibition of tumor growth
What is the MOA for Elspar?
Catalyzes asparagine into ammonia and aspartic acid. Some malignant cells are unable to synthesize asparagine and are dependent on exogenous asparagine for DNA and protein synthesis
What is the drug classification for palladia?
Tyrosine kinase inhibitor
What is the MOA for Palladia?
Competitively inhibits ATP binding in target receptor tyrosine kinases, preventing receptor phosphorylation and subsequent downstream signal transduction.
What is the MOA for zoledronate?
impedes osteoclast activity and induces osteoclast apoptosis to inhibit bone resorption. Increases urinary excretion of calcium and phosphorus
What is the drug classification for zoledronate?
bisphosphanate
