Term
| What type of drugs interfere with the synthesis of DNA? |
|
Definition
| Antimetabolites -Folic Acid Analogs -Pyrimidine -Purine analogs and related inhibitors |
|
|
Term
| What are the Pyrimidine analogs? |
|
Definition
|
|
Term
| What 3 Mechanisms does Methotrexate have? |
|
Definition
| 1. Inhibitor of DHFR-> decreased syn of purines (main mech) 2. Inhibitor of thymidylate synthetase-> decreased syn of thymine 3. Inhibitor of early enzymes in original syn of inosine monophosphate |
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Term
| What is administered ~24 hrs after methotrexate administration? |
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Definition
Leucovorin Provides reduced folate for metabolism b/c limiting the available reduced folate in the body
(also given with Fluorouracil, but for different reason) |
|
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Term
| Once methotrexate is taken up into the cells, what happens? |
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Definition
undergoes polyglutamation-> trapping it inside cells
-> inhibits TS and 2 early enzymes in the purine biosynthetic pathway |
|
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Term
| At Low concentrations, how does Methotrexate act as a DMARD? |
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Definition
| inhibition of conversion of adenosine to inosine-> increased conc. of adenosine-> inhibits IL-receptors-> decreases inflammation |
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|
Term
| How does resistance develop to 5-Fluorouracil? |
|
Definition
| Decreased activation of 5-FU mutation of TS Upregulation of TS |
|
|
Term
| What are the toxicities of Fluorouracil? |
|
Definition
|
|
Term
| How is Leucovorin Tx used for Fluorouracil? |
|
Definition
| To drive proliferation (rapidly dividing cells are more sensitive to tx) Increase formation of TS complex-> enhanced response to 5-FU |
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|
Term
| How does Gemcitabine differ from Cytarabine in its mechanism? |
|
Definition
| Kinetic Difference 1 additional base-pair is added after its incor-> masked termination-> removal/repair is more difficult |
|
|
Term
| What is the mechanism of the Purine analogs? |
|
Definition
Mercaptopurine
provide false building blocks to be incorp into DNA Synthesis |
|
|
Term
| What purine analog is metabolized via HGPRT? |
|
Definition
|
|
Term
| Which purine analog is broken down by xanthine oxidase? |
|
Definition
| 6-mercaptopurine (use Allopurinol to block xanthine oxidase) |
|
|
Term
| What is the Vinca alkaloid Natural Product? |
|
Definition
|
|
Term
| What is the mechanism Vincrastine? |
|
Definition
| bind to beta-tubulin-> blocks tubulin polymerization(assembly)-> metaphase arrest-> apoptosis |
|
|
Term
| At what stage does the cell cycle arrest when using Vincristine? |
|
Definition
|
|
Term
| What causes resistance to the Vinca alkaloids (Vincrisstine)? |
|
Definition
P-glycoprotein (pumps drugs from tumor cells)
BCRP
MRP |
|
|
Term
| What toxicities does Vincristine possess? |
|
Definition
| Neurotoxicity Hair loss local cellulities |
|
|
Term
| What are the predictable cumulative effects of vincristine? |
|
Definition
| Numbness and tingling of extremities Loss of DTR Loss of motor function |
|
|
Term
| What is the effect of inadvertent intrathecal vincristine administration? |
|
Definition
| Fatal Central Neurotoxicity with seizures and irreversible coma |
|
|
Term
| What is the mechanism of Topotecan? |
|
Definition
| stabilize DNA-topo I cleavable complex |
|
|
Term
| What is essential for Topotecan activity? |
|
Definition
| Conformation - requires planar ring to intercalate between 2 strands of DNA |
|
|
Term
| What is the Podophyllotoxin? |
|
Definition
|
|
Term
| What is the mechanism of Etoposide? |
|
Definition
| form comples with topo-II and DNA |
|
|
Term
| Resistances to Podophyllotoxins (Etoposide)? |
|
Definition
| increase efflux mutation decrease topo-II expression or changes in structure p53 mutation |
|
|
Term
| What is the mechanism of the Taxanes (Paclitaxel)? |
|
Definition
| bind beta-tubulin-> blocks disassembly-> metaphase arrest-> apoptosis |
|
|
Term
| How are the Taxanes metabolized? |
|
Definition
|
|
Term
| What Taxane causes "stocking glove" sensory neuropathy? |
|
Definition
|
|
Term
| What are the multiple mechanisms of Doxorubicin? |
|
Definition
Intercalate w/ DNA affecting transcription and replication
Complex w/ topo-II and DNA
Free radical generation from semiquinone-> cellular damage |
|
|
Term
| Which drug produces Red urine? |
|
Definition
|
|
Term
| What is the mechanism of Bleomycin? |
|
Definition
| drug-Fe complex oxidizes deoxyribose of thymidylate and other nucleotides -> single, double strand DNA breaks |
|
|
Term
| What Toxicity do Bleomycin cause? |
|
Definition
Pulmonary Toxicity -
Dry cough-> Fibrosis |
|
|
Term
| What is the mechanism of Actinomycin D? |
|
Definition
| Intercalates DNA adjacent to G-C base pairs -> single strand DNA breaks |
|
|
Term
| What causes side effects of desquamation, inflammation, and pigmentation in areas previously x-rayed? |
|
Definition
|
|
Term
| What agent decreases availabilty of asparagine for protein synthesis? |
|
Definition
|
|
Term
| What is important about Asparaginase parenteral administration? |
|
Definition
| with other drugs, sequence is important! |
|
|
Term
| How is Asparaginase Produced? What's a Potential Fatal hypersensitivity because of this? What's a Safer alternative? |
|
Definition
Microorganisms
Serratia
Pegaspargase |
|
|
Term
| What miscellaneous agent is a free radical scavenger? |
|
Definition
|
|
Term
| What are the 4 mechanisms of Thalidomide? |
|
Definition
Inhibits tumor cell proliferation
Inhibits tumor cell adhesion to stroma
Inhibits angiogenesis
Enhances NK cell activity |
|
|
Term
| What agent causes degradation of chimeric gene in acute PML? (promyelocytic leukemia) |
|
Definition
Tretinoin
(Disrupts fusion of PML and RARa genes -> differentiation) |
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