Chemotherapy and radiotherapy Flashcards
Exposure to toxins encourages body to…
switch on metabolising enzymes.
Drugs now prescribed with…
associated biomarker test.
Active drug
Metabolism reduces activity
Prodrug
Activates when metabolised
Pharmacodynamics
Focusses on drug targets
What is the mainstay of cancer treatment?
SACT
What are some benefits of IV drug delivery?
Avoids first pass metabolism and therefore variation
Hospital setting - better monitoring
Capecitabine
Taken orally and metabolised to 5fu
Which is better tolerated: carboplatin or cisplatin?
carboplatin
Tamoxifen is metabolised to endoxifen, by ______, which is more biologically active.
cip2d6
What is a monoclonal antibody against EGFR (prescribed with biomarkers?)
Cetuximab
cip2d6
more likely to be inactive or overactive in some ethnicities
Drugs targeting ras could be effective for which cancer?
Pancreatic
What is the problem with a wider range of targets (kras)
Loses cell activity for cancer
Phase 1 metabolism
Oxidation by CP450
Phase 2 metabolism
Conjugation by transferases
Phase 3 metabolism
Extrusion by ABC and SLC
Which cancers are most chemosensitive?
Haematological
Germ cell
Lung
Breast, ovarian, Cervical
Lymphoma
Melanoma
Which cancers are least chemosensitive?
Renal
Cholangiocarcinoma
Pancreatic
Gastric
Liver
Bladder
Nasal
Chemotherapy side effects
Myelosuppression
Immunosuppression
Fatigue
Anaemia
Mucositis
Alopecia
Support drugs for chemotherapy
Analgesics
Anti-emetics
Steroids
Laxatives
Sometimes antibiotics
What does radiotherapy use?
Ionising radiation
What is a benefit of radiotherapy?
Less selective than surgery and chemotherapy
What makes energy dangerous?
Quantisation (highly condensed energy)
Radiotherapy ________ could be reduced without negatively impacting outcomes.
fractions
Why do we need to wait for a half life to be completed before another dose?
To allow complete cell repair
Which cells are more radioresistant?
Hypoxic cells that proliferate
What does leaving time between doses allow?
Previously hypoxic cells receive oxygen and become radiosensitive
Which method of treatment is preferred because it makes repopulation more difficult?
Shorter treatment (3-4 weeks)
Radiotherapy risk
Can form cancer stem cells
Radiotherapy can stimulate or inhibit immune responses. How can it stimulate the immune system?
Cytokines, MHC expression
Flash radiotherapy
Treatment times of seconds rather than minutes - cell killing is oxygen independent
Brachytherapy
Radioactive sources in tumours
Hyperthermia
Heat doesn’t get conducted away from the tumour due to poor blood flow
Hyperbaric oxygen
Feeding more oxygen to the tumour
Proton beam therapy
Energy is delivered as particles which gives peaks of energy
Microwaves upset pacemakers
Theranostics
Combine diagnostic nuclear medicine imaging, to validate target expression and estimate radiation dose, with therapeutic approaches, to identify suitable patients for treatment.
How does radiation damage DNA?
Directly
Indirectly (ROS)
How are SSBs repaired?
BER (base excision repair)
How are DSBs repaired?
NHEJ
What are DAMPs?
damage-associated molecular patterns that act as pro inflammatory signals
What determines the biological effect of radiation?
Type of radiation
Number of fractions Interval between fractions
Overall time
Dose rate
Tissue type
Individual variation
Densely ionising energy causes more biological damage. Give some examples.
neutron beam therapy
carbon-ions
alpha particles
Give an example of a DAMP produced by radiation
Calretinin which binds to dendritic cells
Dangers of radiotherapy
fibrosis
impaired growth
atrophic skin
telangiectasia
ulceration
What is the biological advantage of high dose rates?
cell killing is independent of the oxygen concentration
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