Anticancer

Question 1

Azothioprine, 6-Mercaptopurine MOA

Answer 1

Purine analogs activated by HGPRT, decrease de novo purine synthesis

Question 2

Azothioprine, 6-Mercaptopurine Toxicity

Answer 2

Myelosuppression, GI, Liver.

Drugs are metabolized by Xanthine Oxidase, therefore, increased toxicity with Allopurinol

Question 3

Cladribine MOA

Answer 3

Purine analog, causes inhibition of DNA Polymerase and DNA strand breaks

Question 4

Cladribine Toxicity

Answer 4

Myelosuppression, nephrotoxic, neurotoxic

Question 5

Cytarabine MOA

Answer 5

Pyrimidine analog, inhibition of DNA Polymerase

Question 6

Cytarabine Toxicity

Answer 6

(Pancytopenia) Leukopenia, Thrombocytopenia, Megaloblastic anemia

“Hand-Foot” Syndrome

Question 7

5-Fluorouracil MOA

Answer 7

Pyrimidine analog, activated by 5F-dUMP which complexes with folic acid. This complex inhibits Thymidylate Synthase - decreases dTMP and DNA synthesis

Question 8

5-Fluorouracil Toxicity

Answer 8

Myelosuppression, “Hand-Foot” Syndrome

Question 9

Methotrexate MOA

Answer 9

Folic acid analog - DHFR competitive inhibitor.
Thymidylate Synthase inhibitor, and inhibits other enzymes in purine biosynthesis (leads to an accumulation of Adenosine)

Question 10

Methotrexate Toxicity

Answer 10

Myelosuppression (reversable with Leucovorin”rescue”), Pulmonary Fibrosis, Hepatotoxicity, Mucositis

Question 11

Bleomycin MOA

Answer 11

Induces free radical formation resulting in in DNA strand breaks

Question 12

Bleomycin Toxicity

Answer 12

Pulmonary fibrosis, skin hyperpigmentation, mucositis

Question 13

Dactinomycin MOA

Answer 13

Intercalates in DNA. Myelosuppression.

Question 14

Doxorubicin, Daunorubicin MOA

Answer 14

Generates free radicals, and intercalates in DNA resulting in DNA strand breaks

Question 15

Doxorubicin, Daunorubicin Toxicity

Answer 15

Cardiotoxicity (dilation), myelosuppression, alopecia.

Dexrazoxane is an Fe-chelating agent given to prevent cardiotoxicity

Question 16

Busulfan MOA

Answer 16

Alkylating agent that cross-links DNA

Question 17

Busulfan Toxicity

Answer 17

Pulmonary fibrosis, hyperpigmentation, myelosuppression

Question 18

Cyclophosphamide MOA

Answer 18

Alkylating agent that preferentially acts on the N7 guanine and does inter and intrastrand cross-linking. Requires activation by liver.

Question 19

Nitrosoureas (Carmustine/Lomustine) MOA

Answer 19

Alkylating agent, DNA cross-linking. Cross BBB to have CNS effects. Requires bioactivation.

Question 20

Nitrosoureas (Carmustine/Lomustine) Toxicity

Answer 20

CNS toxicity (convulsions, dizziness, ataxia)

Question 21

Taxanes (Paclitaxel) MOA

Answer 21

Hyperstabilize microtubules in M-phase, prevents spindle breakdown

Question 22

Vinca Alkyloids (Vincristine/Vinblastine) MOA

Answer 22

Bind B-tubulin to prevent microtubule polymerization

Question 23

Vinca Alkyloids (Vincristine/Vinblastine) Toxicity

Answer 23

Neurotoxicity, paralytic ileus

Question 24

Cisplatin/Carboplatin MOA

Answer 24

Intra-strand cross-links in DNA

Question 25

Cisplatin/Carboplatin Toxicity

Answer 25

Progressive peripheral neuropathy, nephrotoxic, ototoxic (acoustic nerve damage). Amifostine (free radical scavenger) to prevent nephrotoxicity

Question 26

Etoposide MOA

Answer 26

Inhibits Topoisomerase II, increasing DNA degradation

Question 27

Irinotecan/Topotecan MOA

Answer 27

Inhibits Topoisomerase I (DNA Gyrase) prevents unwinding

Question 28

Hydroxyurea MOA

Answer 28

Free Radical Scavenger, prevents RNA to DNA conversion (inhibits Ribonucleotide Reductase)

Question 29

Hydroxyurea Toxicity

Answer 29

Desquamanitive Interstitial Pneumonitis, Skin toxicity

Question 30

Bevacizumab MOA

Answer 30

Mab against VEGF, inhibits angiogenesis

Question 31

Bevacizumab Toxicity

Answer 31

Hemorrhage, blood clots, impaired wound healing

Question 32

Erlotinib MOA

Answer 32

EGFR Tyrosine Kinase inhibitor

Question 33

Imatinib MOA

Answer 33

BCR-ABL TKI and c-kit

Question 34

Rituximab MOA

Answer 34

Mab against CD-20, B-cell neoplams

Question 35

Tamoxifen MOA

Answer 35

Selective Estrogen Receptor Modulator

Question 36

Trastuzumab/Herceptin MOA

Answer 36

Mab against HER-2

Question 37

Trastuzumab/Herceptin Toxicity

Answer 37

Cardiootoxicity ("Heartceptin")

Question 38

Vemurafenib MOA

Answer 38

TKI of BRAF in melanoma