Anti-neoplastic Agents 2 - Antimetabolites

Question 1

Antimetabolites: Purine Analog - 6-Mercaptopurine (6MP) MOA and Reduce dose when?

Answer 1

Activated by HGPRT to 6-thioinosinic monophosphate –> inhibition of purine nucleotide synthesis

Reduce dose if given with allopurinol

Question 2

Antimetabolites: Purine Analog - 6-thioguanine (6TG) (1)

Answer 2

No dose modification with allopurinol

Question 3

Antimetabolites: Pyrimidine Antagonists - 5-fluorouracil (5FU) (MOA (2)

Answer 3

5FU –> Fdump

Inhibits thymidylate synthase –> thymineless death

Question 4

Antimetabolites: Pyrimidine Antagonists - 5-fluorouracil (5FU) Toxicities (4)

Answer 4

1. Nausea
2. Mucositis (esophageal ulcers)
3. Diarrhea
4. Hand and foot syndrome

Question 5

Antimetabolites: Pyrimidine Antagonists - 5-fluorouracil (5FU) Capecitabine MOA

Answer 5

Convereted to fluorouracil in the tumor

Question 6

Antimetabolites: Pyrimidine Antagonists - 5-fluorouracil (5FU) Cytarabine Dependent and Use

Answer 6

Highly schedule dependent (S phase)

Used in acute myelogenous leukemia

Question 7

Antimetabolites: Folate Antagonist - Methotrexate (MTX) MOA (4)

Answer 7

Inhibits dihydrofolate reductase (DHFR)

Tetrahydrofolate not synthesized

Inhibits DNA, RNA, and protein synthesis

Question 8

Antimetabolites: Folate Antagonist - Normal cells require folic acid, so what do we do?

Answer 8

Leucovorin rescue (folinic acid)

Antidote to methotrexate toxicity

Question 9

Antimetabolites: Others - Hydroxyurea Use (2)

Answer 9

Used for CML

Used for Sickle Cell Anemia (low dose) –> increase fetal Hbf synthesis

Question 10

3. Antibiotics (Anthracyclines): Doxorubicin and Daunorubicin MOA (3)

Answer 10

1. Inhibits topoisomerase II
2. Binds to DNA through intercalation blockade of the synthesis of DNA and RNA, and DNA strand scission
3. Generation of semiquinone free radicals

Question 11

3. Antibiotics (Anthracyclines): Doxorubicin and Daunorubicin Side Effects (3) and Antidote

Answer 11

1. Cardiotoxicity (side effects)
2. Acute: pericarditis, arrythmia, ECG changes
3. Chronic: CHF

Antidote: Dexrazoxane (prevents CHF) - chelating agent

Question 12

3. Antibiotics (Anthracyclines): Radiation Recall Reaction - Bleomycin MOA

Answer 12

Causes DNA strand scission

Question 13

3. Antibiotics (Anthracyclines): Radiation Recall Reaction - Bleomycin Side effects (2)

Answer 13

1. Pulmonary toxicity (pneumonitis with cough, dyspnea, rales, infiltrates)
2. Skin (redness, hyperpigmentation, and skin tenderness)

Question 14

4. Mitotic Inhibitors: Vinca Alkaloids MOA (2)

Answer 14

Bind to tubulin: block microtubular polymerization

Cell division is arrested in meta phase

Question 15

4. Mitotic Inhibitors: Vinca Alkaloids - Vinblastine Side Effects (2)

Answer 15

1. Bone marrow suppression

2. Alopecia (side effect)

Question 16

4. Mitotic Inhibitors: Vinca Alkaloids - Vincristine Side Effects (1)

Answer 16

Peripheral neuropathy

Question 17

4. Mitotic Inhibitors: Vinca Alkaloids - Vinorelbine Side Effect (1)

Answer 17

Bone Marrow Suppression

Question 18

4. Mitotic Inhibitors: Taxanes - Paclitaxel (Taxol) MOA

Answer 18

Enhancement of tubulin polymerization

Question 19

4. Mitotic Inhibitors: Taxanes - Paclitaxel (Taxol) Rx of (3)

Answer 19

1. Breast cancer
2. Lung cancer
3. Ovarian cancer

Question 20

4. Mitotic Inhibitors: Taxanes - Docetaxel Rx of (1)

Answer 20

Advanced breast cancer

Question 21

4. Mitotic Inhibitors: Taxanes - Paclitazel and Docetaxel are metabolized by?

Answer 21

Cytochrome P450

Question 22

5. Miscellaneous: Topoisomerase Inhibitors - 2 types and use

Answer 22

1. Etopside and Teniposide: lung cancer

2. Irinotecan and Topotecan: colorectal cancer

Question 23

5. Miscellaneous: Enzymes - L-Asparaginase MOA

Answer 23

Catalyses hydrolysis L-asparagine to aspartic acid (tumor cells require L-asparagine for growth)

Question 24

5. Miscellaneous: - L-Asparaginase Side Effects (1)

Answer 24

Pancreatitis

Question 25

5. Miscellaneous: Tyrosine Kinase Inhibitors - Imatinib (GLEEVEC) MOA (2) and Use (1)

Answer 25

Inhibitor of tyrosine kinase domain bcr-able oncoprotein Prevents the phosphorylation of kinase substrate by ATP First line therapy in chronic phase of CML and blast crisis

Question 26

5. Miscellaneous: Tyrosine Kinase Inhibitors - Vemurafenib (2)

Answer 26

1. B-raf enzyme inhibitor | 2. Used in melanoma patients whose cancer has a V600E BRAF mutation

Question 27

5. Miscellaneous: Growth Factor Receptor Inhibitors - Gefitinib (IRESSA) and Erlotinib (TARCEVA) MOA

Answer 27

Inhibitor of the tyrosine kinase domain assoicated with the EGFR (epidermal growth factor receptor) Used in non-small cell lung cancer

Question 28

5. Miscellaneous: Growth Factor Receptor Inhibitors - Cetuximab (ERBITUX)

Answer 28

EGFR inhibitor used in metastatic colorectal cancer

Question 29

5. Miscellaneous: Growth Factor Receptor Inhibitors - Rituximab (RITUXAN) Target and Use (2)

Answer 29

Attacks CD20 Used in B cell lymphoma

Question 30

5. Miscellaneous: Growth Factor Receptor Inhibitors - Trastuzamab (HERCEPTIN) Target and Use

Answer 30

HER2/Neu (ErbB-2) Used in breast cancer

Question 31

5. Miscellaneous: Growth Factor Receptor Inhibitors - Lapatinib (TYKERB) Chemo protocols

Answer 31

Hodgkin's Disease: ABVD region Adriamycin (doxorubicin) Bleomycin Vinblastine Dacarbazine

Question 32

Resistance to Chemotherapy: Formation of cancer drug inactivating enzymes

Answer 32

6-mercaptopurine and 5-FU

Question 33

Resistance to Chemotherapy: Decrease of binding affinity and drug sensitivty (4)

Answer 33

1. Etoposide 2. Methotrexate 3. Vincristine 4. Vinblastine

Question 34

Resistance to Chemotherapy: Decrease drug accumulation or permeability (3)

Answer 34

1. Methotrexate 2. Dactinomycin 3. Cyclophosphamide

Question 35

Resistance to Chemotherapy: Chemical Reactions Inactivating Chemotherapy (3)

Answer 35

1. Cyclophosphamide 2. Bleomycin 3. Cisplatin

Question 36

Resistance to Chemotherapy: Increased nucleic acid repair mechanism (2)

Answer 36

1. Cisplatin | 2. Cyclophosphamide

Question 37

Resistance to Chemotherapy: Reduced activation of pro-drgs 2)

Answer 37

1. 6-mercaptopurine | 2. 5 FU

Question 38

Resistance to Chemotherapy: Multdrug resistances MOA (2)

Answer 38

1. Increased expression of MDR1 gene for P-glycoprotein | 2. Overexpression of the multidrug resistance protein 1 (MRP1_ t