Chemotherapy Drugs Flashcards
What are the five main classes of chemotherapy?
Anti-metabolites Spindle poisons Alkylating agents DNA intercalater DNA Scissions
Describe anti-metabolites
Two main drugs
Methotrexate - inhibits dihydrofolate reductase, meaning that cell is unable to produce tetrahydrofolate. Reduce folate production -> decreased purine and pyrimidine production -> decreased DNA synthesis
5-Fluorouracil- analogue of uracil, converted to 5FdUMP. This competes with DUMP for thymidilate synthase as well as binding to another co-enzyme which produces a stable complex which cannot release any product. Causes thymidine-less cell death.
Describe spindle poisons
Vinca alkaloids and taxanes
VA - vincristine and vinblastine
polymerises beta-tubulin sub-unit to prevent microfilament formation. This arrests the cell cycle and causes apoptotic cell death.
Taxanes - paclitaxel
stabilises the microtubules and prevents their disassembly therefore they cannot pull the chromosome apart and the cell is stuck in metaphase. Also stimulates apoptotic cell death.
Describe alkylating agents
Cause covalent bonds to form between DNA. Either intrastrand or interstrand and prevent further replication from occuring. Have maximum effect in the S phase as most DNA is exposed in this phase. e.g. Cisplatin
Describe DNA intercalaters
Two methods of action
Anthrcycline antibiotics
Have a molecule ring structure binds between base pairs and interferes with normal transcription and translation. Generate free radicals by binding to free Fe2+, which further damages DNA. Effect on Topoisomerase II
Interference prevents repair of DNA and the damaged DNA triggers apoptosis. Are non-cell cycle specific.
Describe DNA Scission
Bleomycin
Has two effects
1. Binds to DNA via terminal -NH2 and by intercalation
2. Chelates free Fe2+, catalysing superoxide and free radical production. These attack phosphodiester bonds, cutting or casing scission of the DNA strands. Most effective in G2.
What causes pulmonary toxicity in DNA scission chemotherapy?
Free radical production in the lungs.
Give some main side effects of chemotherapy
Vomiting Diarrhoea Mucositis Skin lesions Vasculitis Alopecia Myalgia Kidney failure Cardiotoxicity Pulmonary fibrosis Neurotoxicity Myelosuppression Impaired wound healing
Why do you get renal failure in chemotherapy?
Chemotherapy causes increase breakdown of tumour cell, which leads to an increase in purines being released. This increases purine metabolism, causing increased release of urates. Precipitation of urate crystals will occur in the renal tubules and can lead to renal failure and death.
What is a significant side effect of antimetabolites?
Renal failure in methotrexate treatment
What is a significant side effect of anthracycline antibiotics?
Cardiotoxicity- due to doxorubicin and daunorubicin producing free radicals
What is a significant side effect of Bleomycin?
Bleomycin causes significant pulmonary toxicity due to free radical generation
What is a significant side effect of alkylating agents?
Peripheral sensory and motor neuropathy with high doses of cis-platin as well as oto-toxicity
What is a significant side effect of mitotic spinal inhibitors?
Neurotoxicity- glove and stocking peripheral neuropathy
