Classic chemotherapy- part 2

Question 1

what are the 3 main classes of DNA topisomerase inhibitors?

Answer 1

• Anthracyclines
• Mitoxantrone
• Amsacrine

Question 2

what do topoisomerase inhibitors do?

Answer 2

they intercalate with DNA

Question 3

what is DNA intercalating?

Answer 3

where the drugs slots inbetween the DNA bases and make them elongate and cause a kink the phosphate backbone. Increases the length of DNA and causes unwinding

Question 4

what is the mechanism of action of anthracyclines?

Answer 4

-Anthracyclines inhibit DNA Topoisomerase II
• Most antitumour intercalators inhibit this enzyme
• Enzyme crucial to DNA unwinding during replication

Question 5

what is doxorubicin?

Answer 5

its a type of anthracycline which is a type of topoisomerase inhibitor

Question 6

what does doxorubicin?

Answer 6

creates a tertiary complex of DNA, doxorubicin and topoisomerase can’t recognise DNA and gets stuck in topoisomerase so DNA splits in half.

Question 7

what is the toxicity of topoisomerase inhibitors?

Answer 7

• cardiotoxicity stems from the redox chemistry of the anthracycline
• generates superoxide and hydrogen peroxides

Question 8

what is the main mechanism of resistance for topoisomerase inhibitors?

Answer 8

increased expression of P-glycoproteins and increased efflux from the cell

Question 9

what are the other topoismoerase II inhibitors?

Answer 9

• mitoxantrone
• amsacrine
• etoposide

Question 10

what is a topoisomerase 1 inhibitor?

Answer 10

camptothecin