Pharmacology 2011 - Antineoplastics (Test 3)

Front 1

Cell cycle phases

Back 1

1. G0- resting phase
2. G1- RNA/Protein synthesis
3. S- DNA synthesis
4. G2- pre-mitotic interval
5. M-mitosis

Front 2

What are cyclin-dependent kinases (CDKs)?

Back 2

enzymes that control the transitions between phases of cell cycle

Front 3

What is cancer?

Back 3

disruption of cell cycle

Front 4

5 objectives of chemotherapy treatment

Back 4

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

Front 5

Decision to use chemotherapy (and which agent to use) is based on what 5 things?

Back 5

1. Tumor type
2. Stage of malignancy
3. Patient condition
4. Tumor responsiveness to chemotherapy
5. Constraints of owner: financial, time, emotional

Front 6

What is the main consideration when picking an effective treatment for cancer?

Back 6

Effective treatment requires a balance between toxicity to cancer cells and toxicity to normal cells

Front 7

What type of cells do cancer drugs target?

Back 7

o Cancer chemotherapy drugs are designed to target cells rapidly undergoing cell cycling

Front 8

Do chemotherapeutic agents have a wide or narrow therapeutic index?

Back 8

Chemotherapeutic agents have a narrow therapeutic index

Front 9

What are some common toxicities associated with chemotherapy drugs?

Back 9

* Bone marrow suppression
* GI disturbances
* Alopecia
* Breeding deficiencies

Front 10

6 Reasons for therapeutic failure of chemotherapy drugs?

Back 10

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

Front 11

What can cause therapeutic failure in 90% of patients with metastatic cancer?

Back 11

Resistance

Front 12

6 causes of resistance to cancer drugs?

Back 12

 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

Front 13

What are the 3 types of Alkylating agents used as antineoplastic drugs?

Back 13

1.Nitrogen mustards
2.Nitrosoureas
3.Platinum coordination complexes

Front 14

What 2 antineoplastic drugs are nitrogen mustards (alkylating agents)?

Back 14

1. Cyclophosphamide
2. Chlorambucil

Front 15

MOA/Primary toxicity of nitrogen mustards (Cyclophosphamide & Chlorambucil)

Back 15

* Alkylates DNA strand and changes it structure

Severe bone marrow suppression

Front 16

What type of drug is Cyclophosphamide and how is it activated?

Back 16

Pro-drug and activated by metabolism through CytP450)

Front 17

When using Cyclophosphamide what is an indicator to stop terapy?

Back 17

Associated with sterile necrotizing hemorrhagic cystitis seen in both dogs and cats

Front 18

What 2 antineoplastic drugs are nitrosoureas(alkylating agents)?

Back 18

1. Lomustine (CCNU)
2. Carmustine (BCNU)

* high lipid solubility (used against tumors in CNS)

Front 19

MOA/Primary toxicity of nitrosoureas (Lomustine & Carmustine)

Back 19

Bifunctional alkylating agents—form DNA-DNA and DNA-protein links (esp. at guanine)

* Severe bone marrow suppression

Front 20

What 2 Platinum coordination complex drugs were discussed in class?

Back 20

Cisplatin and Carboplatin

Front 21

MOA of Platinum coordination complex drugs (Cisplatin and Carboplatin)

Back 21

Alkylation of DNA

Front 22

Major toxicity caused by Platinum coordination complex drugs (Cisplatin and Carboplatin)

Back 22

Nephrotoxicity!!!

•Cisplatin – contraindicated in cats!
•Carboplatin – less nephrotoxic; can be used in cats

Front 23

What species is Cisplatin contraindicated in?

Back 23

Cisplatin – contraindicated in cats!

Front 24

Cisplatin and Carboplatin which is less nephrotoxic?

Back 24

Carboplatin – less nephrotoxic; can be used in cats

Front 25

MOA of antimetabolites (antineoplastic drugs)

Back 25

Antimetabolites are all cell cycle specific (S Phase)

* Inhibit DNA Synthesis

Front 26

2 types of antineoplastic drugs that are antimetabolites

Back 26

1. Folic Acid analogs
2. Pyrimidine analogs

Front 27

Drug discussed in class that is a folic acid analog (antimetablite antineoplastic drug)

Back 27

Methotrexate

Front 28

2 drugs discussed in class that is a pyrimidine analog (antimetablite antineoplastic drug)

Back 28

1. 5-flurouracil
2. Cytarabine

Front 29

MOA of Methotrexate

Back 29

Inhibits dihydrofolate reductase

Front 30

Major toxicity of Methotrexate

Back 30

Myelosuppression; can precipitate in renal tubules at high doses

Front 31

MOA of 5-flurouracil

Back 31

Inhibit thymidylate synthase – alters DNA/RNA synthesis

Front 32

Major toxicity of 5-flurouracil

Back 32

Myelosuppression; crosses into CNS

Toxic to cats!

Front 33

MOA of Cytarabine

Back 33

•MOA: Inhibit DNA synthesis

Front 34

Major toxicity of Cytarabine

Back 34

Bone marrow suppression

Front 35

What are the 3 categories of natural products that are antineoplastic drugs?

Back 35

1. Vinca alkaloids
2. Anthracyclines
3. Enzymes

Front 36

MOA of Vinca alkaloids

Back 36

anti-mitotic; inhibit function of microtubules

* cell cycle specific (M Phase)

Front 37

2 vinca alkaloid drugs

Back 37

1. Vincristine sulfate
2. Vinoblastin sulfate

Front 38

MOA of Vincristine sulfate

Back 38

anti-mitotic; inhibit function of microtubules

* cell cycle specific (M Phase)

Front 39

Major toxicity of Vincristine sulfate

Back 39

extravasation, mild bone marrow suppression, peripheral neuropathy (rare)

Front 40

MOA of Vinoblastin sulfate

Back 40

anti-mitotic; inhibit function of microtubules

* cell cycle specific (M Phase)

Front 41

Major toxicity of Vinoblastin sulfate

Back 41

extravasation, more severe myelosuppression, peripheral neuropathy (rare)

Front 42

Are anthracyclines cell cycle specific?

Back 42

NO

Front 43

Example of a antineoplastic anthracycline drug

Back 43

Doxorubicin

Front 44

MOA of Doxorubicin

Back 44

topoisomerase inhibitor which prevents religation of DNA

Front 45

Major toxicity of Doxorubicin

Back 45

Extravasation, dose related cardiotoxicity

Front 46

Are antineoplastic enzyme drugs cell cycle specific?

Back 46

YES: Cell cycle specific (G1 phase)

Front 47

Example of an antineoplastic enzyme drug

Back 47

L-asparaginase

Front 48

MOA of L-asparaginase

Back 48

catalyzes hydrolysis of asparagines

Front 49

Major toxicity of L-asparaginase

Back 49

anaphylaxis

Front 50

Example of an antineoplastic Cyclooxygenase inhibitor

Back 50

Piroxicam

Front 51

Major toxicity of Piroxicam

Back 51

GI effects; nephrotoxicity