Cancer Chemotherapy Flashcards
Name some alkylating agents.
- Platinum based: cisplatin, which is used to treat testicular cancer.
What is the mechanism of action of alkylating agents?
- Forms cross links in the two DNA strands preventing a break and DNA replication.
What other chemotherapy class of drug prevents DNA replication?
- Intercalating agents.
Why are alkylating agents less effective at targeting tumour cells?
- Tumour cells have a pump that recognises alkylating agents and pumps it back out of the cell - target the pump.
- Glutathione inside the cell mops is the active moiety of alkylating agent, neutralising it.
Name some anti metabolites.
- Methotrexate
- 5-fluorouracil
Mechanism of action of methotrexate and 5-fluorouracil.
- Methotrexate is used in haematological malignancies - inhibits DHFR so lack of folate production means no DNA synthesis.
- 5-F inhibits thymidylate synthase causing DNA damage.
Name some spindle poisons?
- Taxoids
- Vinca alkaloids
Mechanism of action of spindle poisons
- Disrupt microtubule dynamics in pre-metaphase stage.
Mechanism of action of Taxoids
-Taxoids promote the assembly and prevent the disassembly, making the spindle fibres/ microtubules so rigid that the cell cannot divide.
Mechanism of action of Vinca Alkaloids
- Prevent spindle formation by binding to tubulin and preventing polymerisation, arresting the cell in the M phase.
General side effects of chemotherapy drugs
- Alopecia
- Mucositis as gut renewal rapidly occurs. Usually in the oropharynx and presentation of sore throat, diarrhoea, GI bleed.
- N + V
- Inflammatory diarrhoea
- Cystitis
- Myelosuppression
- Pulmonary fibrosis
Organ system side effects of chemotherapy drugs
- Renal failure
- Acute renal failure from hyperuricaemia caused by rapid tumour lysis leading to precipitation of urate crystals in renal tubules.
- GI perforation at site of tumour - seen in lymphoma.
- DIC - especially in acute myeloid leukaemia.
- Skin toxicity - irritation and thrombophlebitis of veins.
- Cardio-toxicity - arrhythmias, cardio-myopathy.
Contraindications
- Antifungals = exacerbates neuropathy
- Warfarin = risk of bleeding as chemo decreases platelet count
- Penicillin
- NSAIDs
- Supplements Such as St Johns Wort
All these drugs increase the plasma level of the chemo drug - has a narrow therapeutic window.
What should you monitor when prescribing cancer chemo drugs?
- Creatinine clearance to monitor renal function
- ECG to monitor heart function
What type of drugs should you avoid with chemotherapy drugs?
- Cytotoxic drugs because they exacerbate the haematological toxicity = death.
