Chemotherapy drugs Flashcards
What are the 6 classes of cytotoxic drugs?
- Alkylating drugs
- Platinating drugs
- Anti-metabolites
- Cytotoxic antibodies
- Mitotic inhibitors
- Topoisomerase inhibitors
What is the mechanism of action of alkylating agents?
The reactive alkyl group forms covalent bonds with DNA, crosslinking DNA & disrupting its replication & transcription
What are the 2 alkylating drugs?
Cyclophosphamide, chlorambucil
What are the 3 methods of resistance to alkylating agents?
- Decreased entry into or increased exit of agent from cell
- Inactivation of agent in cell
- Enhanced repair of DNA lesions produced by alkylation - upregulation of DNA repair genes
What are the 4 general side effects of chemotherapy?
- Myelosuppression
- Nausea, vomiting, GI effects
- Mucous membrane ulceration
- Alopecia
What is the mechanism of action of platinum-based chemotherapy drugs?
Platinum-based drugs act as alkylating agents, causing intra-strand crosslinks hence disrupting DNA replication & transcription
What are the 3 platinum-based chemotherapy drugs?
cisplatin, carboplatin, oxaliplatin
What are the adverse effects of platinum-based chemotherapy drugs?
Nephrotoxicity as excreted renally; contraindicated in patients with renal dysfunction
Cisplatin & oxaliplatin may cause peripheral sensory neuropathy
What is the mechanism of action of anti-metabolites?
Anti-metabolites interfere with the synthesis of nucleotides purine & pyramidine, inhibiting DNA replication
What are the 2 cell-cycle specific chemotherapy drugs?
Anti-metabolies & mitotic inhibitors
What are the 4 cell-cycle non-specific chemo drugs?
Alkylating, platinum-based, cytotoxic antibiotics & topoisomerase inhibitors
What are the 2 anti-metabolites?
Methotrexate & 5-fluorouracil
What is the mechanism of action of methotrexate?
Methotrexate is an anti-metabolite that inhibits dihydrofolate reductase, preventing thymidine monophosphate synthesis
What is the mechanism of action of 5-fluorouracil?
5-fluorouracil is an anti-metabolite which inhibits thymidylate synthase (TS) and is used in place of uracil, hence causing DNA damage
What are the clinical indications for methotrexate?
Lymphoma & breast cancer
What are the clinical indications of 5-fluorouracil?
Colorectal cancer
What are the 4 mechanisms of action of cytotoxic antibiotics?
- Inhibit DNA & RNA synthesis by intercalating base pairs along DNA strands
- Create free O2 radicals that damage DNA & cell membranes
- Inhibit topoisomerase II
- Alter membrane fluidity & ion transport
What are the 2 cytotoxic antibiotics?
Doxurubicin, daunorubicin
What is the mechanism of action of Vinca alkaloids?
Vinca alkaloids disrupt the function of microtubules by binding to polymerising end of the beta subunit of tubulin, preventing elongation of the microtubule
What is the mechanism of action of taxanes?
Taxanes disrupt the function of microtubules by binding to the beta subunit of tubulin, stabilising the microtubule and preventing shortening or depolymerisation
What are the 2 classes of mitosis inhibitors?
Vinca alkaloids & taxanes
What is the mechanism of action of topoisomerase inhibitors?
Topoisomerase inhibitors interfere with the transcription and replication of DNA by disrupting appropriate DNA supercoiling due to inhibition of Topoisomerase I/II
What is an example of a Vinca alkaloid?
Vinblastine
What is an example of a taxane?
Paclitaxel
What is an example of a type 1 topoisomerase inhibitor?
Irinotecan
What is an example of a type 2 topoisomerase inhibitor?
Etoposide
