Chemo Flashcards
Why do chemo drugs only work on actively dividing cells
They don’t work in the G0 phase, only S phase
Describe fractional kill hypothesis
Chemo drugs need to be given in stages to prevent excessive loss of bone marrow cells whilst allowing tumour cell levels to fall to necessary levels
Classes of chemo drugs and their site of action
Alkylating agents (DNA synthesis) Antimetabolites (DNA synthesis) Spindle poisons (mitosis) Intercalating agents (DNA transcription)
How do alkylating agents work using an example
Cisplatin allows covalent bonds to form between DNA strands which creates platinated inter and intra strand adducts
This inhibits DNA synthesis
Give examples of antimetabolites
Methotrexate
5-fluorouracil
MoA of methotrexate
Inhibits DHFR to inhibit folate synthesis so the cell can’t produce purines for DNA
MoA of 5-FU
5-FU is activated to 5-FdUMP which inhibits thymidylate synthase so pyramidines can’t be incorporated into DNA
Examples of spindle poisons and their MoA
Vinca alkaloids - inhibit polymerisation of microtubules to inhibit mitosis
Taxoids - cause excessive polymerisation of microtubules which inhibits their depolymerisation so sister chromatids can’t move apart during mitosis
Mechanisms of chemo resistance
Decreased drug entry
Increased drug exit
Inactivation of drug within cell e.g glutathione
Enhanced DNA repair
What factors affect whether someone is suitable for chemo
Type of malignancy Performance score Stage Tumour markers Prognostic score
Routes of chemo administration
IV - Hickman line into subclavian vein PO SC Into cavity Intralesional Intrathecal (into CSF) Topical
Factors requiring dose alteration
Liver and renal function Body surface area General health (will outcome outweigh side effects?)
When is a cancer clinically detectable
When it contains x10^9 cells
When does a cancer cause host death
When it contains x10^12 cells
Describe the log kill ratio and it’s relevance to early intervention for cancer
Log kill ratio is the x10^n tumour cells killed
Need to ensure chemo doesn’t allow the tumour to grow but also doesn’t kill too many healthy cells that would cause host death
Therefore outcome improved in early intervention, before clinically detectable
List 14 side effects of chemo and which one is most often the dose limiting effect
Vomiting Alopecia Skin toxicity Mucositis Cardiotoxicity Lung toxicity Haematological toxicity - DOSE LIMITING AKI GI perforation at tumour site Myelosuppression Phlebitis Myalgia Infertility Neuropathy
Why does chemo cause vomiting and how can it be prevented
Acts on central chemoreceptor trigger zone
Give serotonin or dopamine antagonists
Which chemo drugs cause the highest incidence of alopecia
Doxorubicin
Vinca alkaloids
Cyclophosphamide
Examples of chemo drugs that commonly cause skin toxicity
Bleomycin - hyperkeratosis, hyperpigmentation, ulcerated pressure sores
Doxorubicin/cyclophosphamide - hyperpigmentation
What are Beau’s lines
Horizontal lines in fingernails due to some chemo drugs
Examples of chemo drugs that commonly cause cardiotoxicity
Doxorubicin - cardiomyopathy
Cyclophosphamide - arrhythmia
Example of chemo drug that commonly causes lung toxicity
Bleomycin - lung fibrosis
How might chemo cause AKI
Hyperkalaemia and hyperuricaemia following tumour lysis
How are cancers monitored during chemo
Cancer response - markers, imaging
Drug level and side effects
Organ damage - creatinine clearance, ECG
