Cytotoxic Agents Summary

Question 1

What is an example of an alkylating agent, it’s mechanism of action and AEs?

Answer 1

Cyclophosphamide

Alkylating agents cause crosslinking of DNA

AEs of cyclophosphamide:

• haemorrhagic cystitis
• myelosuppression
• transitional cell carcinoma

Question 2

What is the mechanism of action of bleomycin, and it’s AEs?

Answer 2

Bleomycin is a cytotoxic antibiotic, causing degradation of preformed DNA.

AEs notably include lung fibrosis

Question 3

What is the mechanism of action of doxorubicin, and it’s AEs?

Answer 3

Doxorubicin is a cytotoxic antibiotic, which stabilises DNA-topoisomerase II complex, inhibiting DNA and RNA synthesis.

AEs: notably cardiomyopathy, also marrow-toxic

Question 4

What is the mechanism of action of methotrexate, and its significant AEs?

Answer 4

Methotrexate is an antimetabolite, which inhibits dihydrofolate reductase and thymidine synthesis.

AEs include myelosuppression, mucositis, liver and lung fibrosis.

Question 5

What is Fluorouracil (5-FU)’s MoA and it’s significant AEs?

Answer 5

pyrimidine anologue inducing cell cycle arrest and apoptosis by blocking thymidate synthase (works in S phase)

Largely causes myelosuppression, mucositis, dermatitis

Question 6

What is the mechanism of action of 6-mercaptopurine and its AEs?

Answer 6

purine analogue that is activated by HGPRTase, which reduces purine synthesis

major AE is myelosuppression

Question 7

What is the mechanism of cytarabine, and its AEs?

Answer 7

Pyrimidine antagonist, specifically interferes with DNA synthesis specifically at the s-phase of cell cycle and inhibits DNA polymerase

AEs: Myelosuppression, ataxia

Question 8

What is the mechanism of action of vincristine/vinblastine and their AEs?

Answer 8

inhibits formation of microtubules.

Vincristine causes reversible peripheral neuropathy and ileus.

Vinblastine causes myelosuppression

Question 9

What is the mechanism of action of docetaxel and it’s AEs?

Answer 9

prevents microtubule depolymerisation and disassembly, decreasing free tubulin.

AEs are predominantly neutropenia

Question 10

What is the mechanism of action of cisplatin and its AEs?

Answer 10

causes cross linking of DNA.

Primary AEs are ototoxicity, peripheral neuropathy and hypomagnesaemia

Question 11

What is the mechanism of action of hydroxyurea, and its AEs?

Answer 11

inhibits ribonucleotide reductase, reducing DNA synthesis.

Major AEs are myelosuppression.