Chemotherapy

Question 1

Big picture - what is chemotherapy?

Answer 1

Targeted Toxicity.

Question 2

Why are tumor cells more vulnerable to chemotherapy drugs than normal cells?

Answer 2

They contain lots of mitotic cells dividing all the time.

Question 3

What is the log-kill effect?

Answer 3

Drugs kill a constant fraction of cells, not a specific number. You need to know the fractional kill and the number of tumor cells to calculate how many courses of chemo you are going to need to eliminate the population completely.

Question 4

Chemotherapy drug toxicities

Answer 4

Proliferating normal cells - skin, hair, blood, GI mucosa - so the symptoms include hair loss, skin cracking, anemia, and nausea/vomiting.

Question 5

Cell cycle specific drugs

Answer 5

DNA synthesis inhibitors and mitotic inhibitors

Question 6

Cell cycle non-specific drugs

Answer 6

Alkylating agents

Question 7

How do cancers become resistant to chemo?

Answer 7

Mutation or gene expression changes.

Question 8

Methotrexate mechanism of action

Answer 8

Inhibits DNA synthesis by blocking dihydrofolate reductase, - blocks thymidine synthesis.

Question 9

Methotrexate ADME and toxicity

Answer 9

PO, IV, dose dependent absorption - lower is faster
Renal elimination
Toxicity - hepatotoxic long term
crystalizes urine - renal damage, reduce dose in renal impairment.

Question 10

Flourouracil mechanism of action

Answer 10

Thymidine analog - terminates DNA synthesis. Also Inhibits thymidylate snythetase - blocks thymidine synthesis.

Question 11

Flourouracil ADME and toxicity

Answer 11

IV or Topical for skin cancers. Metabolized to active drug. Renal Excretion
Tox - Nausea, vomiting, myelosuppression. oral, GI ulceration.

Question 12

Hydroxyurea mechanism of action

Answer 12

Inhibits ribonucleotide reductase, which forms deoxyribonucleotides from ribonucleotides.

Question 13

What is hydroxyurea useful for, besides chemotherapy

Answer 13

Sickle Cell - promotes Hemoglobin F formation by suppressing erythrocyte precursors.

Question 14

Hydroxyurea Toxicities

Answer 14

Leukopenia, Anemia, occasional thrombocytopenia
TERATOGENIC
GI disturbances, mild dermatologic reactions

Question 15

Cyclophosphamide mechanism of action

Answer 15

Alkylating Agent - Crosslinks DNA, preventing replication and transcription - DNA-DNA crosslinks
Also damages bases and creates DNA to protein crosslinks.

Question 16

Cyclophosphamide ADME

Answer 16

PO/IV, completely absorbed. Prodrug - metabolized to active form, which is phosphoramide mustard. Also creates toxic metabolite - acrolein.

Question 17

Cyclophosphamide Toxicity

Answer 17

Alopecia, N, V, myelosuppression, hemorrhagic cystitis due to acrolein toxicity