Cytotoxic Drugs Flashcards
What is the mechanism of action of cyclophosphamide?
Alkylating agent
Causes cross-linking in DNA
What adverse effects are associated with cyclophosphamide?
Haemorrhagic cystitis
Myelosuppression
Transitional cell carcinoma
What is the mechanism of action of bleomycin?
Cytotoxic antibiotic
Degrades preformed DNA
What adverse effects are associated with bleomycin?
Lung fibrosis
What is the mechanism of action of anthracyclines (such as doxorubicin)?
Cytotoxic antibiotic
Stabilises DNA-topoisomerase II complex, inhibits DNA & RNA synthesis
What adverse effects are associated with anthracyclines (such as doxorubicin)?
Cardiomyopathy
What is the mechanism of action of methotrexate?
Antimetabolite
Inhibits dihydrofolate reductase and thymidylate synthesis
What adverse effects are associated with methotrexate?
Myelosuppression
Mucositis
Liver fibrosis
Lung fibrosis
What is the mechanism of action of fluorouracil (5-FU)?
Antimetabolite
Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase).
What adverse effects are associated with antimetabolites?
Myelosuppression
Mucositis
Dermatitis
What is the mechanism of action of 6-mercaptopurine?
Antimetabolite.
Purine analogue that is activated by HGPRTase, decreasing purine synthesis
What adverse effects are associated with 6-mercaptopurine?
Myelosuppression
What is the mechanism of action of cytarabine?
Antimetabolite.
Pyrimidine antagonist. Interferes with DNA synthesis (specifically at S-phase) and inhibits DNA polymerase
What adverse effects are associated with cytarabine?
Myelosuppression
Ataxia
How do antimetabolites work?
Antimetabolites are drugs that interfere with one or more enzymes, or their reactions, that are necessary for DNA synthesis.
Antimetabolites are structurally similar enough to natural enzymes to replace them but different enough to interfere with their role.
What are examples of antimetabolites?
Methotrexate
Fluorouracil
6-mercaptopurine
Cytarabine
What is the mechanism of action of vincristine?
Inhibits formation of microtubules
What adverse effects are associated with vincristine?
Peripheral neuropathy (reversible)
Paralytic ileus
What is the mechanism of action of vinblastine?
Inhibits formation of microtubules
What adverse effects are associated with vinblastine?
Myelosuppression
What is the mechanism of action of docetaxel?
Prevents microtubule depolymerisation and disassembly, decreasing free tubulin.
What adverse effects are associated with docetaxel?
Neutropenia
What is the mechanism of action of irinotecan?
Topoisomerase inhibitor
Inhibits topoisomerase I, which prevents relaxation of supercoiled DNA
What adverse effects are associated with irinotecan?
Myelosuppression
What is the normal role of topoisomerases?
Topoisomerases (or DNA topoisomerases) are enzymes that participate in the overwinding or underwinding of DNA.
The winding problem of DNA arises due to the intertwined nature of its double-helical structure. During DNA replication and transcription, DNA becomes overwound ahead of a replication fork.
Topoisomerase inhibitors (such as irinotecan) inhibit these enzymes and prevent DNA being unwound.
What is the mechanism of action of cisplatin?
Cisplatin causes cross-linking in DNA
What adverse effects are associated with cisplatin?
Ototoxicity
Peripheral neuropathy
Hypomagnesaemia
What is the mechanism of action of hydroxyurea (hydroxycarbamide)?
Inhibits ribonucleotide reductase, decreasing DNA synthesis
What adverse effects are associated with hydroxyurea (hydroxycarbamide)?
Myelosuppression
Myelosuppression is a common side effect of cytotoxic drugs. Which of the main cytotoxic drugs are NOT significantly associated with myelosuppression?
(in brackets = target)
Cisplatin (DNA cross-linking)
Docetaxel (microtubules)
Vincristine (microtubules)
Bleomycin (degrades preformed DNA)
Anthracyclines (DNA synthesis)
Which cytotoxic drug is associated with peripheral neuropathy?
Vincristine is associated with peripheral neuropathy
Cisplatin also associated
Which cytotoxic drug is associated with haemorrhagic cystitis?
Cyclophosphamide is associated with haemorrhagic cystitis
Which cytotoxic drug is associated with lung fibrosis?
Bleomycin is associated with lung fibrosis
Which cytotoxic drug is associated with cardiomyopathy?
Doxorubicin is associated with cardiomyopathy.
Doxorubicin is an example of anthracycline.
Which cytotoxic drug is associated with oto- and nephro- toxicity?
Cisplatin is associated with ototoxicity and nephrotoxicity
Try and draw the toxicity bear! The key is on the other side of this card
A = Asparagine: Neurotoxic
C = Cisplatin: Ototoxic and nephrotoxic
V = Vincristine: Peripheral neuropathy
V = Vinblastine: Myelosuppression
(Christine is nervous; Blast my bones!)
B = Bleomycin: Pulmonary fibrosis
D = Doxorubicin: Cardiomyopathy
Psi = Cyclophosphamide: Haemorrhagic cystitis
M = Methotrexate: Nephrotoxic and myelosuppression
A 62-year-old woman who is known to have metastatic breast cancer presents with increasing shortness of breath. She is currently receiving a chemotherapy regime. On examination she has a third heart sound and the apex beat is displaced to the 6th intercostal space, anterior axillary line. Which one of the following chemotherapeutic agents is most likely to be responsible?
A) Bleomycin B) Dactinomycin C) Docetaxel D) Doxorubicin E) Paclitaxel
D) Doxorubicin
Anthracyclines (e.g. doxorubicin) may cause cardiomyopathy.
