Antibiotics/Anti-Tumor agents

Question 1

Differentiate MOAs of topoisomerase I vs topoisomerase II

Answer 1

I: single stranded DNA breaks –> arrest of replication fork
II: double stranded DNA breaks –> inhibition of chromosomal replication (?)

Question 2

List the intercalating topoisomerase II drugs

Answer 2

Anthracyclines (danorubicin, doxorubicin, mitoxantrone, dactinomycin)

Question 3

List the intercalating topoisomerase I drug

Answer 3

Etoposide

Question 4

Which three chemo drug classes are all cross resistant. Why?

Answer 4

Intercalating and non-intercalating topoisomerase II drugs, and tubulin inhibitors are all cross resistant due to a P-glycoprotein that acts as a membrane bound efflux pump.

Question 5

What two methods may help reverse resistance to the topoisomerase II and tubulin inhibitor drugs?

Answer 5

1) continuous infusion of the drugs may down regulate the glycoprotein expression and lead to reversal of inhibition
2) Quinine, verapamil, and cyclosporine may block the action of the efflux pump and reverse resistance

Question 6

What is the dose limiting toxicity of doxorubicin?

Answer 6

Myelosuppression

Question 7

Is the cardiotoxicity of doxorubicin schedule dependent or independent?

Answer 7

Cardiac toxicity is schedule dependent- longer infusion times are less cardiotoxic.

This works because the tumor cytotoxic effect is schedule independent

Question 8

What can we pre-treat with before administration of doxorubicin to prevent cardiac damage?

Answer 8

Dexrazoxane- iron chelator

Question 9

How do we treat early vs. late diarrhea associated with irinotecan?

Answer 9

Early -Atropine (diarrhea is cholinergic)

Late- (7-10 days)- Imodium, hydration (diarrhea is secretory)

Question 10

Who is at greater risk for myelosuppression and diarrhea with irinotecan (and therefore must be tested beforehand)?

Answer 10

People with Gilbert’s disease- UGT1A1*28 mutation decreases glucoronidation

Question 11

What is the MOA of bleomycin?

Answer 11

Free radical damage to DNA

Question 12

Why are there lung and skin issues seen with bleomycin?

Answer 12

Lung and skin cannot inactivate the drug because they don’t have bleomycin hydrolase like in the liver and kidney

Question 13

What is the dose limiting toxicity of bleomycin?

Answer 13

Pulmonary toxicity- it is a cumulative toxicity

Question 14

What intervention should be avoided in people taking bleomycin?

Answer 14

High oxygen concentrations —> increases free radical damage in the lungs

Question 15

Prednisone is used in the treatment of which cancers?

Answer 15

Myeloproliferative or lymphoproliferative disorders: lymphoma, Hodgkins, non-hodgkins lymphoma, some form of leukemias..