Anticancer Abx

Question 0

Anthracenedione

Answer 0

Mitoxantrone

Question 1

Anthracyclines (5)

Answer 1

Doxarubicin
Duanorubicin 
Idarubicin 
Epirubicin
Valrubicin

Question 2

Actinomycin

Answer 2

Dactinomycin

Question 3

Mitomycin anti cancer antibiotic

Answer 3

Mitomycin

Question 4

Bleomycin anti cancer antibiotic

Answer 4

Bleomycin

Question 5

Anticancer ABX General MOAs

Cell cycle non specific, dose dependent, Anti tumor Abx

Answer 5

1. Intercalation w/ DNA
2. Inhibition of topoisomerase II activity
3. Generation of free radicals that cause single strand DNA breaks

Question 6

Superoxide dismutase

Answer 6

Protective. Detoxifies ROS. Enzyme converts superoxide into hydrogen peroxide

Question 7

Catalase

Answer 7

Protective. Takes hydrogen peroxide and converts it to 2H2O and O2

Question 8

Fenton rxn

Answer 8

Hydrogen peroxide in the presence of Fe2+ will produce hydroxyl free radicals (responsible for ssDNA breaks)

Question 9

Anthracyclines acute cardiotoxicity

Answer 9

Cardiac tissue does not contain catalase enzyme so all hydrogen peroxide produced from quinone + NADPH/CYP450 reductase rxn gets channeled to form hydroxyl radical
Acute cardiotoxicity reduced by administering with dexrazoxane drug will chelate with iron to prevent Fenton rxn

Question 10

Anthrcyclines ADR

Answer 10

Acute and chronic toxicity
Myelosuppression 
N/V
Mucositis 
Alopecia

Question 11

Anthracyclines chronic cardiotoxicity

Answer 11

Aldoketoreductase enzyme reduces C13 keto grp to 2’ OH (rubicinol). Smaller R-group, Faster conversion to 2’OH, increased concentration of active drug accumulating in cardiomyocytes leading to cardiomyopathy

Question 12

Benefits of anthracycline liposomal formulations

Answer 12

Slow plasma clearence
Increase uptake in tumor cells
Decrease uptake in cardiac tissues
Decreased conversion to 2'OH
Decrease extravasation

Question 13

EPIrubicin benefits

Answer 13

EPImer. Faster glucuronidation, eliminated faster. Less ROS generation because of steric hindrance of 4-beta-OH. Less cardiotoxicity than duanorubicin and doxorubicin

Question 14

How does valrubicin void cardiotoxicity?

Answer 14

It is directly delivered into bladder to treat BCG-refractory cancer

Question 15

Mitoxantrone differences from anthracyclines

Answer 15

Lacks l-duanosamine sugar
3 rings instead of 4
Limited ROS formation bc quinone structure in drug is involved in hydrogen bonding
Resistant to NADPH/CYP450 reduction–> dec. Cardiotoxicity
Glucuronide conjugate causes DARK BLUE sclera, fingernails, & urine

Question 16

Anthracyclines MOA

Answer 16

1. Intercalation w/ DNA

2. Inhibition of topoisomerase II activity

Question 17

Anthracenedione (mitoxantrone) MOA

Answer 17

1. Intercalation w/ DNA

2. Inhibition of topoisomerase II activity

Question 18

Actinomycin (dactinomycin) MOA

Answer 18

1. Intercalation w/ DNA

3. Generation of free radicals that cause single strand DNA breaks

Question 19

Dactinomycin toxicities

Drug is Used in wilms tumor in children

Answer 19

Dose limiting myelosuppression
Severe vesicant
N/V
Hyperpigmentation 
Rhabdomyolysis (*avoid HMG-coA reductase inhibitors)
*Radiation recall*

Question 20

Mitomycin MOA

Answer 20

3. Generation of free radicals that cause single strand DNA breaks (from quinone structure)
   Also involved in DNA cross linking (rRNA target?)

Question 21

Mitomycin toxicity

Answer 21

Severe myelosuppression
Skin necrosis
Fatal pulmonary toxicty

Question 22

Bleomycin MOA

Answer 22

3. Generation of free radicals that cause single strand DNA breaks

Question 23

Bleomycin toxicity

Answer 23

• Pulmonary toxicity*
• Skin toxicity*
• NO MYELOSUPPRESSION
• bleomycin in is inactivated by bleomycin hydrase* (amide to carboxylate to lose DNA binding affinity)

Question 24

Mechanisms of Resistance to Anticancer Abx

Answer 24

1. Decrease uptake into tumor cells
2. P-go mediated efflux of drug
3. Reduced expression of target enzyme or mutation of enzyme that decreases binding of drug (I.e topo II)
4. Trapping of ROS (cancer cell can increase glutathione production to decrease ROS)