B. Cancer Chemotherapy III (Topisomerase inhibitors. inhibitors of mitotic spindle)

Question 1

list the microtubules inhibitors (mitotic spindle inhibitors)

Answer 1

Vincristine
Vinblastine
Docetaxel
Paciltaxel

Question 2

which phase in the cell cycle do the microtubule inhibitors affect?

Answer 2

M phase (CCS)

Question 3

what are microtubules inhibitors?

Answer 3

natural products (plant-derived substances), used as anticancer drugs

Question 4

how do the microtubules inhbitors work?

Answer 4

they interfere with the process of mitotic spindle formation by affecting the equilibrium between the polymerized and depolymerized forms of the microtubules–> resulting in cytotoxicity

Question 5

what does Vincristine do?

Answer 5

inhibits microtubules polymerization (‘spindle poison’)

Question 6

what is Vincristine and Vinblastine?

Answer 6

Vinca alkaloids

Question 7

what is Docetaxel and Paciltaxel?

Answer 7

naturally occurring taxanes

Question 8

what does Docetaxel do?

Answer 8

inhibits microtubules disassembly into tubulin monomers

Question 9

indications for Vincristine

Answer 9

acute leukemia
lymphomas
wilm’s tumor
Neuroblastoma

Question 10

indications for Docetaxel

Answer 10

Breast cancer
ovarian cancer
prostate cancer
lung cancer

Question 11

side effects of Vincristine

Answer 11

neurotoxicity (peripheral neuropathy)
autonomic dysfunction (paralytic ileus)
alopecia
myelosuppression

Question 12

side effects of Docetaxel

Answer 12

myelosuppression (severe neutropenia)
neurotoxicity
hypersensitivity reaction
cardiotoxicity
onycholysis (dissolving nails)
hepatotoxicity

Question 13

list the topoisomerase inhibitors

Answer 13

Etoposide
Teniposide
Irinotecan
Doxorubicin

Question 14

what are Etoposide and Teniposide?

Answer 14

semisynthetic derivatives of the plant alkaloid podophyllotoxin

Question 15

which agents inhibit topoisomerase II?

Answer 15

Etoposide
Teniposide
Doxorubicin
Daunorubicin

Question 16

which agents inhibit topoisomerase I?

Answer 16

Irinotecan

Question 17

which topoisomerase inhibitor is a CCNS?

Answer 17

Doxorubicin

Daunorubicin

Question 18

what is Irinotecan?

Answer 18

1. Semisynthetic derivative of a more toxic drug–> camptothecin
2. prodrug, activated to the posted metabolite SN-38

Question 19

what is Doxorubicin?

Answer 19

an antitumor antibiotics

Question 20

what does doxorubicin cause?

Answer 20

it generates free radicals 
intercalates DNA  (↓ replication)

Question 21

indications of Etoposide and Teniposide

Answer 21

small cell lung carcinoma
germ cell tumors
etoposide–> Kaposi sarcoma
teniposide–> ALL

Question 22

side effects of etoposide

Answer 22

nausea, vomiting
myelosuppression
alopecia

Question 23

Indication of Irinotecan

Answer 23

colon cancer (metastatic disease)

Question 24

side effects of Irinotecan

Answer 24

myelosuppression (severe neutropenia)

Diarrhea

Question 25

indications for doxorubicin

Answer 25

hodgkin's lymphoma 
non-Hodgkin's lymphoma 
breast cancer 
ovarian cancer 
lung cancer (SCLC)

Question 26

side effects of doxorubicin

Answer 26

nausea, vomiting
myelosuppression
alopecia
cardiotoxicity (ECG abnormalities, arrhythmias, cardiomyopathy, CHF) - most problematic!!

Question 27

what drug can protect against cardiotoxicity when giving doxorubicin?

Answer 27

Dexrazoxane

an inhibitor of iron-mediated free radical generation