Alkylating Agents & Topoisomerase Inhibitors - AB

Question 1

Describe the pharmacology of nitrogen mustards?

Answer 1

They work by forming highly reactive carbonium ions that form intrastrand cross linking of DNA. When DNA is badly damaged, p53 will trigger apoptosis.

Question 2

Describe the role of CYP2B6 and CYP3A4 in cyclophosphamide’s efficacy and toxicity.

Answer 2

• CYP2B6 lets cyclophosphamide to be broken down into phosphoramide mustard, causing DNA alkylation.
• CYP3A4 changes cyclophosphamide into chloracetaldehyde. This agent is both nephro- and neuro-toxic.

Question 3

What is the fundamental mechanism of all topoisomerase inhibitors?

Answer 3

Topoisomerase inhibitors work by stopping religation of DNA strand (or strands) after they have been broken, causing cell death.

Question 4

Why would an iron chelator, namely ________________ , be effective in limiting the cardiotoxicity of anthracyclines such as doxorubicin?

Answer 4

Dextrazoxaneworks by stopping free radical formation. This is especially important in preventing cardiotoxicity because the protective enzymes are not present in the heart.