Session 10 - Chemotherapy Flashcards
What are the two types of base in DNA?
Purine - Two ring structure (G&A)
Pyrimidines - One ring structure (C, T & U)
What do the base pairs form between?
G and C
A and T
In which direction do the strands of the DNA double helix run?
Complimentary and anti-parallel to each (top strand 5’ -> 3’, bottom 3’ -> 5’)
What are the three steps of DNA replication?
Initiation
Elongation
Termination
What happens in initiation?
Helicase unravels the DNA double helix. Requires specific proteins to interact with DNA and recruit DNA polymerase (because DNA polymerase can only extend from 3’ ends of pre-existing chains to 5’, a special enzyme primase is required to initiate each strand)
What happens in elongation?
leading strand is replicated from 5’ 3’ as normal. However the lagging strand is replicated discontinuously in Okazaki fragments. These fragments are then joined by DNA ligase from OH group to Phosphate group covalently.
What happens in termination?
Replication forms move from the ends of the DNA strands towards each other. Lead strands move towards lagging strands and vice versa. The terms ‘leading’ and ‘lagging’ have no bearing once ligase has joined up all the fragments.
What are the four main types of chemotherapeutics?
Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons
Name three types of antimetabolites
Methotrexate (folic acid anatgonist)
Fluorouracil (antipyrimidine)
Mercatopurine (antipurine)
How do anti-metabolites work in cancer?
Analogues of normal metabolites act by competition to inhibit DNA
Give two alkylatng agents
Cyclophosphamide
Melphalan
What do alkylating agents do?
Alkyl groups react to form bonds with nucleic acids. This causes cross linking of DNA strands, preventing replication
Name three spindle poisons
Vincristine
Vinblastine
Vinca alkaloids
How do spindle poisons work?
Bind tubulin and inhibit the polymerisation of microtubules that is necessary to form the mitotic spindle. Prevents mitosis, arrests cells at metaphase
Name an intercalating agent?
Dactinomycin
How does dactinomycin work?
Intercalates between base pairs of DNA and inhibits RNA synthesis
Give a few tumours which are highly sensitive to chemotherapy
Lymphomas Germ cell tumours Small cell lung Neuroblastoma Wilm’s tumour
Give a few tumours which are moderately sensitive to chemo
Breast Colorectal Bladder Ovary Cervix
Give a few tumours which are low sensitivity to chemotherapy
Prostate
Renal cell
Brain tumours
Endometrial
What is one thing you must make sure when prescribing chemo?
Make sure treatments do not have overlapping toxicity
Give 7 main ADRs of chemo
Vomiting Alopecia Skin toxicity Mucositis Cardiotoxicity Lung toxicity Haemtological toxicity
How does vomiting occur in chemo?
Direct action of chemotherapy on central chemoreceptor trigger zone
Give three different patterns of emesis in chemotherapy?
Acute phase
Delayed onset
Chronic phase
What is alopecia? What chemodrugs cause it? How can it be corrected?
o Hair thins at 2-3 weeks o May be total o May regrow during therapy o Marked with Doxorubicin, Vinca Alkaloids, Cylophosphamide o Minimal with Platinums o Scalp cooling may help
What occurs if the cannula is messed up in chemo?
Local skin toxicity - irritation and thrombophlebitis of veins
What drug causes general skin toxicity?
Bleomycin
Hyperkeratosis
Hyperpigmentation
Ulcerated pressure sores
What is mucositis?
o GI tract epithelial damage
o May be profound and involve the whole tract
o Most commonly worst in Oropharynx
o Presents as sore mouth/throat, diarrhea, GI bleed
What is cardio-toxicity?
o Cardio-myopathy
o Arrhythmias
What occurs in chemo lung toxicity?
o Pulmonary fibrosis
What is haematological toxicity in chemo?
o Most frequent dose limiting toxicity
o Most frequent cause of death from toxicity
o Different agents cause variable effects on degree and lineages
Neutrophils
Platelets
Give five things which can cause variability in chemotherapy pharmacokinetics?
Absorption Distribution Metabolism Elimination Protein binding abnormalities
What can cause variabilities in absorption?
o Nausea and vomiting – May vomit drugs back up
o Compliance
o Gut problems – E.g. mucositis
What can cause variabilities in distribution?
o Nausea and vomiting – May vomit drugs back up
o Compliance
o Gut problems – E.g. mucositis
What can cause variabilities in metabolism
o Liver dysfunction, other medications
What causes variabilities in elimination?
o Renal dysfunction
What causes variability in protein binding?
Low albumin
Drug-drug interacion
Give four important drug-drug interactions in cancer chemotherapy?
o Vincristine and Itraconazole (commonly used antifugngal)
Neuropathy
o Capecitabine (oral 5FU) and Warfarin
Very important interaction!! Increases bleeding risk
o Capecitabine (oral 5FU) and CYP450 enzyme inhibitors
AO-DEVICES
Grapefruit Juice, Omeprazole, Disulfiram, Erythromicin, Valporate, Isoniazid, Cimetidine & Ciprofloxacin, Ethanol (acutely), Sulphonamides
o Methotrexate and penicillin, NSAIDs
How can you monitor the response of tumour to chemotherapy?
o Radiological imaging
o Tumour marker blood tests
o Bone marrow/cytogenics
How can you check chemo drug levels?
o Methotrexate drug assays taken on serial days to ensure clearance from blood after folinic acid rescue
How do you check for chemo organ damage?
o Creatinine clearance
o Echocardiogram
