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Antimetabolites
Pharm Assessment 8
40
Pharmacology
Graduate
10/29/2011

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Cards

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
5- Fluorouracil
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
Term
What is administered ~24 hrs after methotrexate administration?
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)

Term
Once methotrexate is taken up into the cells, what happens?
Definition
undergoes polyglutamation-> trapping it inside cells
-> inhibits TS and 2 early enzymes in the purine biosynthetic pathway
Term
At Low concentrations, how does Methotrexate act as a DMARD?
Definition
inhibition of conversion of adenosine to inosine-> increased conc. of adenosine-> inhibits IL-receptors-> decreases inflammation
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
Hand-Foot Syndrome
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
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
6-mercaptopurine
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
Vincristine
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
metaphase
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
Etoposide
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
Extensive Cyp metabolism
Term
What Taxane causes "stocking glove" sensory neuropathy?
Definition
Paclitaxel
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
Doxorubicin
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
Actinomycin-D
Term
What agent decreases availabilty of asparagine for protein synthesis?
Definition
Asparaginase
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
Hydroxyurea
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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