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51 Cards in this Set

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Cell cycle phases
1. G0- resting phase
2. G1- RNA/Protein synthesis
3. S- DNA synthesis
4. G2- pre-mitotic interval
5. M-mitosis
What are cyclin-dependent kinases (CDKs)?
enzymes that control the transitions between phases of cell cycle
What is cancer?
disruption of cell cycle
5 objectives of chemotherapy treatment
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
Decision to use chemotherapy (and which agent to use) is based on what 5 things?
1. Tumor type
2. Stage of malignancy
3. Patient condition
4. Tumor responsiveness to chemotherapy
5. Constraints of owner: financial, time, emotional
What is the main consideration when picking an effective treatment for cancer?
Effective treatment requires a balance between toxicity to cancer cells and toxicity to normal cells
What type of cells do cancer drugs target?
o Cancer chemotherapy drugs are designed to target cells rapidly undergoing cell cycling
Do chemotherapeutic agents have a wide or narrow therapeutic index?
Chemotherapeutic agents have a narrow therapeutic index
What are some common toxicities associated with chemotherapy drugs?
* Bone marrow suppression
* GI disturbances
* Alopecia
* Breeding deficiencies
6 Reasons for therapeutic failure of chemotherapy drugs?
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
What can cause therapeutic failure in 90% of patients with metastatic cancer?
Resistance
6 causes of resistance to cancer drugs?
 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
What are the 3 types of Alkylating agents used as antineoplastic drugs?
1.Nitrogen mustards
2.Nitrosoureas
3.Platinum coordination complexes
What 2 antineoplastic drugs are nitrogen mustards (alkylating agents)?
1. Cyclophosphamide
2. Chlorambucil
MOA/Primary toxicity of nitrogen mustards (Cyclophosphamide & Chlorambucil)
* Alkylates DNA strand and changes it structure

Severe bone marrow suppression
What type of drug is Cyclophosphamide and how is it activated?
Pro-drug and activated by metabolism through CytP450)
When using Cyclophosphamide what is an indicator to stop terapy?
Associated with sterile necrotizing hemorrhagic cystitis seen in both dogs and cats
What 2 antineoplastic drugs are nitrosoureas(alkylating agents)?
1. Lomustine (CCNU)
2. Carmustine (BCNU)

* high lipid solubility (used against tumors in CNS)
MOA/Primary toxicity of nitrosoureas (Lomustine & Carmustine)
Bifunctional alkylating agents—form DNA-DNA and DNA-protein links (esp. at guanine)

* Severe bone marrow suppression
What 2 Platinum coordination complex drugs were discussed in class?
Cisplatin and Carboplatin
MOA of Platinum coordination complex drugs (Cisplatin and Carboplatin)
Alkylation of DNA
Major toxicity caused by Platinum coordination complex drugs (Cisplatin and Carboplatin)
Nephrotoxicity!!!

•Cisplatin – contraindicated in cats!
•Carboplatin – less nephrotoxic; can be used in cats
What species is Cisplatin contraindicated in?
Cisplatin – contraindicated in cats!
Cisplatin and Carboplatin which is less nephrotoxic?
Carboplatin – less nephrotoxic; can be used in cats
MOA of antimetabolites (antineoplastic drugs)
Antimetabolites are all cell cycle specific (S Phase)

* Inhibit DNA Synthesis
2 types of antineoplastic drugs that are antimetabolites
1. Folic Acid analogs
2. Pyrimidine analogs
Drug discussed in class that is a folic acid analog (antimetablite antineoplastic drug)
Methotrexate
2 drugs discussed in class that is a pyrimidine analog (antimetablite antineoplastic drug)
1. 5-flurouracil
2. Cytarabine
MOA of Methotrexate
Inhibits dihydrofolate reductase
Major toxicity of Methotrexate
Myelosuppression; can precipitate in renal tubules at high doses
MOA of 5-flurouracil
Inhibit thymidylate synthase – alters DNA/RNA synthesis
Major toxicity of 5-flurouracil
Myelosuppression; crosses into CNS

Toxic to cats!
MOA of Cytarabine
•MOA: Inhibit DNA synthesis
Major toxicity of Cytarabine
Bone marrow suppression
What are the 3 categories of natural products that are antineoplastic drugs?
1. Vinca alkaloids
2. Anthracyclines
3. Enzymes
MOA of Vinca alkaloids
anti-mitotic; inhibit function of microtubules

* cell cycle specific (M Phase)
2 vinca alkaloid drugs
1. Vincristine sulfate
2. Vinoblastin sulfate
MOA of Vincristine sulfate
anti-mitotic; inhibit function of microtubules

* cell cycle specific (M Phase)
Major toxicity of Vincristine sulfate
extravasation, mild bone marrow suppression, peripheral neuropathy (rare)
MOA of Vinoblastin sulfate
anti-mitotic; inhibit function of microtubules

* cell cycle specific (M Phase)
Major toxicity of Vinoblastin sulfate
extravasation, more severe myelosuppression, peripheral neuropathy (rare)
Are anthracyclines cell cycle specific?
NO
Example of a antineoplastic anthracycline drug
Doxorubicin
MOA of Doxorubicin
topoisomerase inhibitor which prevents religation of DNA
Major toxicity of Doxorubicin
Extravasation, dose related cardiotoxicity
Are antineoplastic enzyme drugs cell cycle specific?
YES: Cell cycle specific (G1 phase)
Example of an antineoplastic enzyme drug
L-asparaginase
MOA of L-asparaginase
catalyzes hydrolysis of asparagines
Major toxicity of L-asparaginase
anaphylaxis
Example of an antineoplastic Cyclooxygenase inhibitor
Piroxicam
Major toxicity of Piroxicam
GI effects; nephrotoxicity