Cytotoxic drugs

Question 1

Protein target in chemo/radio therapy

Answer 1

p53

Question 2

Give examples of cell cycle specific agents

Answer 2

Anti-metabolites - methotrexate, fluorouracil, cytarabine, 6-mercaptopurine

Mitotic spindle inhibitors - Vinca alkaloids, Taxotere (Taxol)

Question 3

Give examples of non-cell cycle specific agents

Answer 3

Alkylating agents – cyclophosphamide
Platinum derivatives – cis-platinum / carboplatin
Cytotoxic antibiotics – bleomycin, anthracyclines (doxorubicin)

Question 4

General/immediate side effects of cytotoxic drugs

Answer 4

Bone marrow suppression
Gut mucosal damage
Hair loss

Question 5

`Why does chemotherapy fail?

Answer 5

Slow tumour doubling time
Tumour ‘sanctuaries’ eg blood brain barrier

Question 6

What is a consequence of intensifying chemotherapy?

Answer 6

Limited by myelosuppression

Question 7

How to overcome myelosuppression that resulted from intensifying chemotherapy

Answer 7

Use haematopoietic growth factors
Combine myelosuppressive / nonmyelosuppressive agents
intensify doses of active drugs (log-linear tumour kill) + stem (progenitor) cell rescue

Question 8

Different patient sources of stem cells for transplantation

Answer 8

Autologous
Allogenic

Question 9

Function of Cyclophosphamide?

Answer 9

Alkylating agent - causes cross-linking in DNA

Question 10

Adverse effects of Cyclophosphamide

Answer 10

Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma

Question 11

Function of Bleomycin

Answer 11

Bleomycin

Question 12

Adverse effects Bleomycin

Answer 12

Lung fibrosis

Question 13

Function of Anthracyclines (e.g doxorubicin)

Answer 13

Stabilises DNA-topoisomerase II complex inhibits DNA & RNA synthesis

Question 14

Adverse effect of Anthracyclines (e.g doxorubicin

Answer 14

Cardiomyopathy

Question 15

Function of Methotrexate

Answer 15

Inhibits dihydrofolate reductase and thymidylate synthesis

Question 16

Adverse effect of Methotrexate

Answer 16

Myelosuppression, mucositis, liver fibrosis, lung fibrosis

Question 17

Function of Fluorouracil (5-FU)

Answer 17

Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)

Question 18

Adverse effect of Fluorouracil (5-FU)

Answer 18

Myelosuppression, mucositis, dermatitis

Question 19

Function of 6-mercaptopurine

Answer 19

Purine analogue that is activated by HGPRTase, decreasing purine synthesis

Question 20

Adverse effect of 6-mercaptopurine

Answer 20

Myelosuppression

Question 21

Function of Cytarabine

Answer 21

Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase

Question 22

Adverse effect of Cytarabine

Answer 22

Myelosuppression, ataxia

Question 23

Function of Vincristine, vinblastine

Answer 23

Inhibits formation of microtubules

Question 24

Adverse effects of Vincristine, vinblastine

Answer 24

Vincristine: Peripheral neuropathy (reversible) , paralytic ileus
Vinblastine: myelosuppression

Question 25

Function of Docetaxel

Answer 25

Prevents microtubule depolymerisation & disassembly, decreasing free tubulin

Question 26

Side effect of Docetaxel

Answer 26

Neutropaenia

Question 27

Function of Irinotecan

Answer 27

Inhibits topoisomerase I which prevents relaxation of supercoiled DNA

Question 28

Adverse effect of Irinotecan

Answer 28

Myelosuppression

Question 29

Function of Cisplatin

Answer 29

Causes cross-linking in DNA

Question 30

Adverse effect of Cisplatin

Answer 30

Ototoxicity, peripheral neuropathy, hypomagnesaemia

Question 31

Function of Hydroxyurea (hydroxycarbamide)

Answer 31

Inhibits ribonucleotide reductase, decreasing DNA synthesis

Question 32

Adverse effects of Hydroxyurea (hydroxycarbamide)

Answer 32

Myelosuppression

Question 33

Give examples of cytotoxics that act on microtubules

Answer 33

Vincristine, vinblastine
Docetaxel

Question 34

Give examples of topoisomerase Inhibitors

Answer 34

Irinotecan