Heme/Onc Drugs

Question 1

Cyclophosphamide mechanism

Answer 1

Crosslink DNA at guanine N-7 (inhibits DNA replication)

Question 2

What drug causes ototoxicity?

Answer 2

Cisplatin/Carboplatin

Question 3

What drug causes peripheral neuropathy?

Answer 3

Vincristine

Question 4

What drugs cause cardiotoxicity? What can you give to prevent this?

Answer 4

1) Doxorubicin (dilated cardiomyopathy) – give Dexrazoxane to prevent this
2) Trastuzumab

Question 5

What drugs cause pulmonary fibrosis?

Answer 5

Bleomycin, Busulfan

Methotrexate

Question 6

What drugs are nephrotoxic? What can you give to prevent this?

Answer 6

Cisplatin/Carboplatin

Prevent with Amifostine and saline (Cl-) diuresis

Question 7

What drug causes hemorrhagic cystitis? What can you give to prevent this?

Answer 7

Cyclophosphamide

Give Mesna to prevent this

Question 8

What drugs cause myelosuppression?

Answer 8

5-FU
6-MP
Methotrexate

Question 9

Vincristine/Vinblastine

Answer 9

vinca alkaloids that are microtubule inhibitors (M phase)

Can cause peripheral neuropathy and constipation

Question 10

6-Mercaptopurine mechanism of action

Answer 10

purine analog that decrease purine synthesis –> dec DNA synthesis (S phase)

Question 11

What metabolizes 6-Mercaptopurine

Answer 11

Metabolized by xanthine oxidase – thus have increased toxicity when taken with allopurinol or Febuxostat (because less xanthine oxidase is available to metabolize 6-MP)

Question 12

Etoposide/Teniposide

Answer 12

inhibits topoisomerase II → inc DNA degradation

o “Etoposide inhibits topoisomerase two”

Question 13

Irinotecan/topotecan:

Answer 13

inhibit topoisomerase I and prevent DNA unwinding and replication

Question 14

Methotrexate mechanism of action and side effects

Answer 14

folic acid analog that inhibits dihydrofolate reductase (DHF reductase) and decreases DNA synthesis
o Causes myelosuppression – reversible with Leucovorin
o Causes pulmonary fibrosis

Question 15

Leucovorin in 5-Fluorouracil and Methotrexate induced myelosuppression

Answer 15

Leucovorin reverses Methotrexate induced myelosuppression but worsens it in 5-FU

Question 16

5-fluorouracil

Answer 16

complexes to folic acid and inhibits thymidylate synthase, causing dec DNA synthesis (S phase)

o Effects are enhanced with addition of Leucovorin (folinic acid)
o Myelosuppression is worsened with administration of Leucovorin

Question 17

Doxorubicin

Answer 17

generates free radicals that cause breaks in DNA (G2 phase)

Causes cardiotoxicity – dilated cardiomyopathy (which can be prevented with Dexrazoxane)

Question 18

Methotrexate mechanism of action and side effects

Answer 18

folic acid analog that inhibits dihydrofolate reductase (DHF reductase) and decreases DNA synthesis
o Causes myelosuppression – reversible with Leucovorin
o Causes pulmonary fibrosis

Question 19

Busulfan

Answer 19

cross links DNA

o Causes Myelosuppression, pulmonary fibrosis, and hyperpigmentation

Question 20

Bleomycin

Answer 20

generates free radicals that create breaks in DNA (G2 phase)

o Causes pulmonary fibrosis and hyperpigmentation

Question 21

Tamoxifen/Raloxifene mechanism and risks

Answer 21

selective estrogen receptor modulators (SERMs) that block the binding of estrogen in estrogen sensitive breast cancers
o Estrogen receptor antagonists in breast and agonists in bone (can promote bone strength)
o Tamoxifen is a partial agonist in endometrial tissue, which inc the risk of endometrial cancer
o Inc in DVT/PE risk

Question 22

Trastuzumab (Herceptin)

Answer 22

Monoclonal Ab against HER-2 a tyrosine kinase receptor
o Helps kill cancer cells that overexpress HER-2
o Useful against HER-2 + breast cancer
o Can cause cardiotoxicity

Question 23

What drugs are microtubule inhibitors and act on the M phase of the cell cycle? How do their mechanisms differ?

Answer 23

Paclitaxel: hyperstabilizes the microtubules in M phase and prevents breakdown of the mitotic spindle

Vincristine/vinblastine: vinca alkaloids that block polymerization of microtubules and prevent microtubule formation (M phase)