Chrmotherapy Flashcards
In which part of the cell cycle are cells not affected by chemotherapy agents?
G0
What are the 3 types of cytotoxic agents?
Alkylating agents e.g. Cisplatin
Anti metabolites e.g. 5FU, methotrexate
Spindle poisons
How do alkylating agents work?
Covalent bonds form between DNA strands preventing replication
What class of drug is 5 fluorouracil and how does it work?
Anti metabolite
Activated to 5 FdUMP which inhibits thymidylate synthase which is required for the production of pyramidines for DNA
What class is methotrexate and how does it work?
Anti metabolite
It works by hitting dihydrofolate reductase which is necessary to form purines, thymines and some amino acids resulting in the cells in unable to form DNA
How do spindle poisons work?
They affect the microtubular structure of the spindles during metaphase either by inhibiting their formation or causing excessive polymerisation
What are the mechanisms of resistance against alkylating agents?
Decreased entry/increased efflux of agent
Inactivation of agent
Enhanced DNA repair
What are some of the ADRs due to the effect of agents on tumour?
AKI - rapid tumour lysis can cause hyperuricaemia leading to precipitations of urate crystals in tubules
GI perforation at site of tumour
DIC
What are some general ADRs of the agents?
Vomiting - direct action on chemoreceptor
Alopecia
Skin toxicity - irritation, thrombolysis of veins, bleomycin (hyperkeratinosis, hyperpigmentation, ulcerated pressure sores)
Mucositis
Cardiomyopathy - doxorubicin, cyclophosphamide
Arrhythmia - cyclophosphamide
Pulmonary fibrosis - bleomycin
What is the major dose limiting toxicity?
Haematological toxicity - neutrophils, platelets
Name some drugs that can increase the plasma concentration of chemotherapy drugs
Vincristine, warfarin, St. John’s wort
