Cancer Chemotherapy Flashcards
where did chemo come from? what was the first chemo agent?
why was it used?
Mustard gas
Used in WW1 and WW2
(caused a drop in their white cell count)
what is mustard gas used for?
to treat leukemia’s and lymphomas
what is Chemotherapy?
is a cancer treatment where medication is used to kill cancer cells,
They stop cancer cells reproducing, which prevents them from growing and spreading in the body.
Chemotherapy is the treatment of cancer with drug therapy – traditionally this applies to cytotoxic drugs
DNA replication process
STRUCTURE OF DNA
Nucleotide = sugar- phosphate-base
what r the purines? pyramidines?
what value of cancer cells, if reached, u cannot treat anymore?
1012
at which point of the cell cycle r the cancer cells at the DORMANT PHASE?
why is this signifcant to know
G0
cuz neither chemotherpay nor radiotherapy will work!
we can use drugs that actually enhance the # of cells so theyre actually IN the cycle>> therefore we can kill them yaaas
why do we not give patients chemotherapy continuously?
explain why TIMING of the pulses of chemo is very crucial!
Understand the concept of the fractional kill ratio in chemotherapy
no, we give them “pulses of chemotherpay”
listen alaa….when u give chemotherpay, u have both reduction in the number of bone marrow cells & tumor cells,
7lu? ok….
BM cells will recover more quicker and more effectively than ur tumor cells, so what u have to do is u have to give ur chemotherapy AGAIN at the time where the BM cells have recovered
overall u’ll see theres a depletion in the # of BM cells and u’ll see that patients towards the end of their treatment start to have more problems w/ their blood count bc the BM is not recovering adequetly, but overall, it will recover better than the tumor cells.
and so the TIMING of the pulses of chemo is very crucial!
what happens if u delay or quicken the timing of the pulses in chemo?
DELAY>> the tumor cells can bounce back in btw
QUICKLY>> can die from problems associated w/ depletion of the BM cells!
Ex: neutropenic sepsis
not all tumors r sensitive to chemotherapy, outline the tumor classes that r sensitive to chemotherapy!
main cytotoxic chemotherapeutic groups and actions at their targets (brief) (4)
- antimetabolites
- Alkylating agents>> works on DNA
- intercalating agents >> works on DNA
- spindle poisons (Mitotic Inhibitors )
Alkylating Agents —–> Mechanism of Action
work like a KEY
forms _bonds_ btw the 2 DNA strands locking them togezer, no replication fork can be made> cell dies via apoptosis!
what is the the major cause of resistence to chemotherapy agents?
bc as busy as we r trying to cause these breaks in our DNA, we’ve got repair mechanisms that r recongzing these bonds and removing them!
so what can be done to prevent that DNA repair process?
we use biologial agents in combination w/ chemo
Antimetabolites——–> Mechanism of Action/ drug names
Microtubule-binding agents affect microtubule dynamics in 2 ways:
– Inhibit polymerization
– Stimulate polymerization and prevent depolymerization
Spindle poisons——>mode of action
vin deasal—-> used frequently for LUNG CANCER
in order for chemo drugs to work, they must get INTO the cell’s nucleus>> where the dna is…so they can have their effect.
what r the 3 main oppertunities for cells to develop resistence?
1- pumps on the cell
2- proteins in the cytoplasm of cell (ex: glutathione>> bind w/ chemotherpy drug)
3- Dna repair mechanisms in the nucleus
clinical indications of chemotherpy?
- cancer (duh)
- other stuff like RA (at low doses can help w/ the inflammatory reaction)
-
Chemotherapy – route of administration
(what is most common)
Name the different IV pumps used
(some drugs given IV, r not just given mara wa7da wa bas, no, they might need several hours)
PICC>> peripherally inserted central catheter
what is hickmans line? why is it tunelled under the skin?
goes into subcalvian vein
cuz if ‘ve got a forgein body under ur skin, u have a risk of infection, but if u tunner it under the skin, uve got all ur macrophages that helping to combat this infection and protect the line from bacteria
SIDE EFFECTS OF CHEMOTHERAPY
every system of the body can be affected by chem!!!!!! bc every cell in the body is replicating
we can get problems not as a direct effect of the chemo itslef, but bc of the effectivness of the tumor….give example…
what is done in the clininc to prevent these effects from occuirng?
giving chemo to someone with an exquisetly sensitive tumor & so tumor cells will rapidly apoptose >>all of those noxious substances r released .
shit like this should never happen, we give them agents which we use before we give the patients the chemotherapy drugs
what r the patient’s # 1 concern about chemotherapy these days?
Vomiting
Multifactorial but includes direct action of chemotherapy drugs on the central chemoreceptor trigger zone
there r different patterns of vomitting too:
– acute phase 4 - 12 hours
– delayed onset, 2 - 5 days later
– chronic phase, may persist up to 14 days
what is anticipatory vomiting?
ANV is nausea and/or vomiting that occurs before a new cycle of chemotherapy is begun, in response to conditioned stimuli such as the smells, sights, and sounds of the treatment room
what can be given to reduce nausea and vommiting?
antiemetics
- serotonin 5-HT3 receptor antagonists: dolasetron (Anzemet), granisetron (Kytril, Sancuso), ondansetron (Zofran, Zuplenz), palonosetron (Aloxi)
- dopamine antagonists: prochlorperazine (Compazine), domperidone (Motilium, not available in the US), olanzapine (Zyprexa)
- NK1 receptor antagonists: aprepitant (Emend), rolapitant (Varubi)
- corticosteroids: dexamethasone (DexPak)
- cannabinoids: cannabis (medical marijuana), dronabinol (Marinol)
what is Alopecia? how can we reduce it?
Alopecia > a hair-loss condition which usually affects the scalp.
- cool the scalp for less than 4 degrees (i7sas chna brain freeze)*
- u have to do this to make this work! wear a tight cold cap! wear it during and after chemo & should be very tightly fitted! or u’ll be bold*
what is this? what has happened here?
SKIN TOXICITY
drug has gotten into the vein except it is tissued! has killed the skin around this area!
- they have to undergoplastic surgery & all of that tissue has to be stripped back right at the tendon! & then they’ll have to have a skin graft over that*!
- this is why we use so many lines now, cuz if uve got a line that is going into one of the big veins, u can avoid this complication!*
how can u tell how many cycles of chemotherapy the patient has had?
by counting the # of lines on their fingers!
cuz everytime u give chemo, their nail stops growing! & when it starts growing again u get a white mark
“bows lines”
what chemo drugs causes hyperpigmentation?
how does mucositis present? where is it most commonly worst?
Mucositis >> w/ secondary infection thrush
can lead to dehydration if happens in GI!
what can bleomycin cause?
Lung Toxicity
what things lie under Cardio-Toxicity ?
- Arrhythmias
- Cardio-myopathy
what is most frequent cause of death from toxicity ?
Haematological Toxicity of Cancer Therapy
Dose needs to be altered for the individual patient based on what 3 things?
- their surface area and/or body mass index
- drug handling ability (ex: liver function, renal function… dependent on the metabolism and excretion routes)
- general wellbeing (performance status and comorbidity)
Treatment phasing needs to take into account the balance between:
– growth fraction
– the ‘cell kill’ of each cycle of the chemotherapy regimen
– marrow and GI tract recovery before next cycle
– how tolerable is the regimen
– both short term organ toxicity and physical side effects and long term damage causing late effects
What causes variability?
• Abnormalities in absorption
• Abnormalities in distribution
• Abnormalities in elimination
• Abnormalities in protein binding
give example for each?
• Abnormalities in absorption
– Nausea+Vomiting, diharrea, gut problems
• Abnormalities in distribution
– Weight loss, reduced body fat, ascites, etc (ex: ovarian cancer> ascites> drug can just sit there and be diltued)
• Abnormalities in elimination
– Liver and renal dysfunction, other meds
• Abnormalities in protein binding
– Low alb, other drugs (ex: esophageal cancer, their alb levels r low)
important drug/other stuff interactions w/ chemo
what can these drug interactions cause?
Other drugs may _increase_ plasma levels of the chemotherapy drug >> therefore side effects
Drugs
- Vincristine and itraconazole (antifungal)>> causes> neuropathy
- Capecitabine (used for breast cancer) (oral 5FU) & warfarin
- Methotrexate – caution with prescribing penicillin, NSAIDs
Other
St Johns Wort & grapefruit juice
why would we want to monitor them during treatment w/ chemo? (3)
how do we do this?
ex: methotrexate>> we gotta monitor its levels really carefully, bc weyre then gonna give an antidote to turn off the action of that drug
aim of chemotherapy is different in different patients,
name some of these different aims…
what is tamoxifin? side effects?
Use> estrogen receptor antagonist- SERM (ant in pic)
Indication:
ER positive in breast cancer
Side effects- (menopausal symptoms)
- decreased risk of osteoporosis
- increased risk of endometrial cancer
- increased risk of thromboembolism
