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51 Cards in this Set
- Front
- Back
Cell cycle phases
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1. G0- resting phase
2. G1- RNA/Protein synthesis 3. S- DNA synthesis 4. G2- pre-mitotic interval 5. M-mitosis |
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What are cyclin-dependent kinases (CDKs)?
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enzymes that control the transitions between phases of cell cycle
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What is cancer?
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disruption of cell cycle
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5 objectives of chemotherapy treatment
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1. Increase patient survival time
2. Improve quality of life 3. Reduce tumor size 4. Reduce or prevent metastasis 5. May not cure cancer, but can slow its growth |
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Decision to use chemotherapy (and which agent to use) is based on what 5 things?
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1. Tumor type
2. Stage of malignancy 3. Patient condition 4. Tumor responsiveness to chemotherapy 5. Constraints of owner: financial, time, emotional |
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What is the main consideration when picking an effective treatment for cancer?
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Effective treatment requires a balance between toxicity to cancer cells and toxicity to normal cells
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What type of cells do cancer drugs target?
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o Cancer chemotherapy drugs are designed to target cells rapidly undergoing cell cycling
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Do chemotherapeutic agents have a wide or narrow therapeutic index?
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Chemotherapeutic agents have a narrow therapeutic index
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What are some common toxicities associated with chemotherapy drugs?
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* Bone marrow suppression
* GI disturbances * Alopecia * Breeding deficiencies |
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6 Reasons for therapeutic failure of chemotherapy drugs?
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1. Incorrect dose
2. Wrong drug 3. Resistance 4. Toxic effects (need to terminate treatment because of severe vomiting, neutropenia) 5. Slow-growing tumor 6. Inability to reach all tumor cells |
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What can cause therapeutic failure in 90% of patients with metastatic cancer?
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Resistance
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6 causes of resistance to cancer drugs?
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Altered absorption, distribution, metabolism, excretion
Tumor blood flow Low drug concentrations Drug inactivation Change in target receptor Repair of drug‐induced damage Increased drug efflux |
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What are the 3 types of Alkylating agents used as antineoplastic drugs?
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1.Nitrogen mustards
2.Nitrosoureas 3.Platinum coordination complexes |
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What 2 antineoplastic drugs are nitrogen mustards (alkylating agents)?
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1. Cyclophosphamide
2. Chlorambucil |
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MOA/Primary toxicity of nitrogen mustards (Cyclophosphamide & Chlorambucil)
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* Alkylates DNA strand and changes it structure
Severe bone marrow suppression |
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What type of drug is Cyclophosphamide and how is it activated?
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Pro-drug and activated by metabolism through CytP450)
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When using Cyclophosphamide what is an indicator to stop terapy?
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Associated with sterile necrotizing hemorrhagic cystitis seen in both dogs and cats
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What 2 antineoplastic drugs are nitrosoureas(alkylating agents)?
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1. Lomustine (CCNU)
2. Carmustine (BCNU) * high lipid solubility (used against tumors in CNS) |
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MOA/Primary toxicity of nitrosoureas (Lomustine & Carmustine)
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Bifunctional alkylating agents—form DNA-DNA and DNA-protein links (esp. at guanine)
* Severe bone marrow suppression |
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What 2 Platinum coordination complex drugs were discussed in class?
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Cisplatin and Carboplatin
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MOA of Platinum coordination complex drugs (Cisplatin and Carboplatin)
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Alkylation of DNA
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Major toxicity caused by Platinum coordination complex drugs (Cisplatin and Carboplatin)
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Nephrotoxicity!!!
•Cisplatin – contraindicated in cats! •Carboplatin – less nephrotoxic; can be used in cats |
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What species is Cisplatin contraindicated in?
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Cisplatin – contraindicated in cats!
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Cisplatin and Carboplatin which is less nephrotoxic?
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Carboplatin – less nephrotoxic; can be used in cats
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MOA of antimetabolites (antineoplastic drugs)
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Antimetabolites are all cell cycle specific (S Phase)
* Inhibit DNA Synthesis |
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2 types of antineoplastic drugs that are antimetabolites
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1. Folic Acid analogs
2. Pyrimidine analogs |
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Drug discussed in class that is a folic acid analog (antimetablite antineoplastic drug)
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Methotrexate
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2 drugs discussed in class that is a pyrimidine analog (antimetablite antineoplastic drug)
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1. 5-flurouracil
2. Cytarabine |
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MOA of Methotrexate
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Inhibits dihydrofolate reductase
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Major toxicity of Methotrexate
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Myelosuppression; can precipitate in renal tubules at high doses
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MOA of 5-flurouracil
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Inhibit thymidylate synthase – alters DNA/RNA synthesis
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Major toxicity of 5-flurouracil
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Myelosuppression; crosses into CNS
Toxic to cats! |
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MOA of Cytarabine
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•MOA: Inhibit DNA synthesis
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Major toxicity of Cytarabine
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Bone marrow suppression
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What are the 3 categories of natural products that are antineoplastic drugs?
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1. Vinca alkaloids
2. Anthracyclines 3. Enzymes |
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MOA of Vinca alkaloids
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anti-mitotic; inhibit function of microtubules
* cell cycle specific (M Phase) |
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2 vinca alkaloid drugs
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1. Vincristine sulfate
2. Vinoblastin sulfate |
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MOA of Vincristine sulfate
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anti-mitotic; inhibit function of microtubules
* cell cycle specific (M Phase) |
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Major toxicity of Vincristine sulfate
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extravasation, mild bone marrow suppression, peripheral neuropathy (rare)
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MOA of Vinoblastin sulfate
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anti-mitotic; inhibit function of microtubules
* cell cycle specific (M Phase) |
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Major toxicity of Vinoblastin sulfate
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extravasation, more severe myelosuppression, peripheral neuropathy (rare)
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Are anthracyclines cell cycle specific?
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NO
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Example of a antineoplastic anthracycline drug
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Doxorubicin
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MOA of Doxorubicin
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topoisomerase inhibitor which prevents religation of DNA
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Major toxicity of Doxorubicin
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Extravasation, dose related cardiotoxicity
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Are antineoplastic enzyme drugs cell cycle specific?
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YES: Cell cycle specific (G1 phase)
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Example of an antineoplastic enzyme drug
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L-asparaginase
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MOA of L-asparaginase
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catalyzes hydrolysis of asparagines
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Major toxicity of L-asparaginase
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anaphylaxis
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Example of an antineoplastic Cyclooxygenase inhibitor
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Piroxicam
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Major toxicity of Piroxicam
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GI effects; nephrotoxicity
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