PMC 2 Anti-Cancer Drugs

CCS
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Terms in this set (68)
CCS
drugs that can only kill cells that are cycling
CCNS
Drugs that can kill cells regardless if they are cycling or resting
primary resistance
using a drug for the first time and it doesn't work
Acquired Resistance
using a drug for the first time and it works but stops working after a while
single drug or class / 2 or more drugs or a class
What are the two types of resistance?
over expression of active efflux pumps
Multi-Drug-resistance is often attributed to
P-glycoprotein and MRP1
What are the two common active efflux pumps?
Diltiazem, verapamil
what are two drugs that can inhibit active efflux pumps?
electrophiles
Polyfunctional alkylating agents are all? *e
CCNS
Polyfunctional Alkylating agents - G.Prop. - they are all____
1. Nausea, Vomiting, Diarrhea / 2. Alopecia / 3. Bone Marrow DepressionWhat are the three toxicities of Polyfunctional Alkylating agents?Bonding to DNA Covalently = DNA DamageWhat is the primary target of Polyfunctional Alkylating agents?mono-functionalcovalently bonding to one strand of DNAbifunctionalcovalently bonding to each strand of DNA1. Increased DNA Repair / 2. Decreased permeability / 3. Increased Glutathione production / 4. Increased glutathione S-Transferase enzymeMOR for Polyfunctional Alkylating Agents?helps protect against electrophilesWhat is the purpose of glutathione?Polyfunctional Alkylating AgentsWhat drug category is cyclophosphamide in?Cyt.P450 in the liverWhat converts cyclophosphamide to its active form?4-hydroxycyclophosphamide which rests in equilibrium with AldophosamideWhat is the active form of cyclophosphamide?Acrolein and Phosphoramide mustardWhat are the toxic metabolites?4-ketocyclophosphamide and CarboxyphosphamideWhat are the inactive metabolites?the livercyclophosphamide is toxic everywhere but where?CCSAll Anti-metabolites are what?inhibit nucleic acid synthesisWhat is the MOA of Anti-metabolites?DNA and Purine SynthesisMethotrexate inhibits_________?biosynthesis of tetrahydrafolic acidMethotrexate is an Antifolate so therefore it inhibits ?methotrexate polyglutamateMethotrexate is converted to _______ to fight cancerFolypolyglutamate synthaseWhat enzyme converts methotrexate to methotrexate polyglutamate?1. exert antifolate activity in the cell / 2. serve as a intracellular storage form of methotrexatemethotrexate polyglutamates do what two things in the cell?1. dihydrofolate reductase / 2. thymidylate / 3. GAR Transformylase / 4. AICAR TransformylaseWhat are the 4 enzymes that methotrexate polyglutamate inhibit?1. Decreased drug transport into cell 2. decreased ability to synthesize methotrexate polyglutamates 3. increased levels of DHFR enzyme 4. expression of altered or mutant form of DHFR 5. Active EffluxWhat are the Resistances for Methotrexate?Bone Marrow DepressionWhat is the toxicity of methotrexate at the regular dose?bone marrow depression and nephrotoxicityWhat is the toxicity of methotrexate at the high dose?LeucovorinWhat drug decreases toxicity of methotrexate at regular doses?1. decrease influx of methotrexate / 2. decrease plasma levels of methotrexate / 3. restore DNA and Purine synthesis in healthy cellsHow does leucovorin work to decrease levels of methotrexate?Leucovorin and GlucarpidaseWhat drugs do you use to decrease methotrexate toxicity at high doses?converts methotrexate to inactive metabolitesHow does glucarpidase work?No, because you will lose efficacy of leucovorin - seperate by 4-6 hourscan you give glucarpidase and leucovorin at the same time? and why?6-thioinosinic acidWhat is the active form of Mercaptopurine?HGPRTMercaptopurine is catalyzed by what enzyme?IMP to AMP and IMP to GMPWhat does Meraptopurine inhibit?1. down regulation of HGPRT / 2. Up-regulation of alkaline phosphatase (inactivates mercaptopurineMOR of Mercaptopurine?1. Bone Marrow Depression / 2. HepatotoxicityToxicities of Marcaptopurine?NO, because you will get high levels of xanthine oxidase in the blood.Can you take Mercaptopurine with a Xanthine oxidase inhibitor (allopurinol)?5-FUTP and 5-dUMPWhat are the active forms of Fluorouracil?inhibit biosynthesis of DNA and RNAMOA of Fluorouracil?RNA synthesis / DNA synthesis5-FUTP inhibits________, and 5-dUMP inhibits _________Leucovorin* because it enhances the anti-cancer activity of FluorouracilWhat drug do you take with Fluorouracil for a synergistic combination, and how does it help?Neurotoxicity and Bone marrow depressionToxicity of Fluorouracil?Uridine Triacetate, and within 4 daysWhat is the antidote for Fluorouracil, and when should it be taken?Uridine TriphosphateWhat is the active form of Uridine Triacetate?Vinblastine, Vinvristine, and VinorelbineWhat are the Vinca Alkaloids?bind to tubulin and effect the cell cycleMOA of Vinca Alkaloids?bone marrow depression **Toxicity of Vinblastine and Vinorelbine?NeurotoxicityToxicity of Vincristine?Etoposide and TeniposideWhat are the Epipodophyllotoxins?CCSAre Epipodophyllotoxins CCS or CCNS?CCS**Are Vinca Alkaloids CCS or CCNS?bone marrow depressionToxicity of Epipodophyllotoxins?Topotecan and IrinotecanWhat are the Camptothecins?CCNSAre Camptothecins CCS or CCNS?inhibit topoisomerase I = DNA damageMOA of Camptothecinsbone marrow depression***Toxicity of Camptothecins?inhibit topoisomerase II = DNA damageMOA of EpipodophyllotoxinsPaclitaxel, Docetaxel, and CabaxitaxelWhat are the taxanes?CCSAre taxanes CCS or CCNS?bind to microtubules which causes polymerization of microtubules and inhibits mitosisMOA of taxanes?cardiac arrythmia, neurotoxicity, bone marrow depressiontoxicity of taxanes?