Chemotherapeutics Flashcards
what is the growth fraction and will it be higher or lower in tumor cells?
growth fraction is the number of cells cycling compared to those in Go…it will be higher in tumors as more are growing
what is the log kill hypothesis for chemo
states that 1 round of chemo will kill 99% of cells around
what are two reasons we use combined chemo against tumors?
- tumors are often hetergenous and will have different genetic problems leading to the tumor
- different parts of the tumor can have different resistances
primary chemotherapy
palliative therapy…cancer progressed and chemo only option
adjuvant chemo
small tumor…surgery first them chemo to follow
neoadjuvant chemo
huge tumor…so chemo first then surgery
radiosensitization chemo
some chemo drugs make cancer more susceptible to radiation so administer chemo then radiation
three general types of chemos in increasing order of toxicity
biologics, targeted inhibitors, traditional
three general types of chemos in increasing order of specificity of target
traditional, targeted inhibitors, biologics
how do phase non specific drugs work and what are they called?
they cross link DNA, so it cannot unwind and replicate or make RNA
alkylating agents
what do alkylating agents have to help cross link?
bifunctional structure to bind at two different spots on the DNA strand and crosslink it
how to get resistance to alkylating agents with repair systems?
increased DNA repair will notice the cross link and lead to ridding of it
two modes are base excision repair and nucleotide excision repair
what is another way to get alkylating agent resistance?
glutathione can bind the agent before it is even able to act on the cell and render it ineffective
cyclophosphamide/Ifosphamide type of chemo drug
alkylating or DNA cross link agent…non specific cell cycle
cyclophosphamide/Ifosphamide toxicity
hemorrhagic cystitis…bladder bleeding
myelosuppression
how does cyclophosphamide/Ifosphamide cause hemorrhagic cystitis?
given in inactive form that is broken down into active form and acrolein…the acrolein causes the bladder bleeding
how to treat toxicity of cyclophosphamide/Ifosphamide?
can give Mensa that will inhibit the acrolein and yield no toxic effects of cyclophosphamide/Ifosphamide
Bleomycin and Busulfan type of chemo drug
alkylating agents…DNA cross link…phase non specific
Bleomycin and Busulfan toxicities
pulmonary fibrosis and myelosuppression
Carmustine type of chemo agent
alkylating…DNA cross link…phase non specific
carmustine side effect/drug interaction
made with alcohol…so alcohol abusers on Antabuse will lead to high levels of acetaldehyde and BAD hangovers
Cisplatin and Carboplatin type of chemo drug
alkylating agent…DNA cross link…stage non specific
Cisplatin and Carboplatin toxicities
renal toxicity
ototoxicity
mechanism of Cisplatin and Carboplatin renal toxicity? treatment?
wasting of K+/Mg2+ leads to renal failure…
treat with hydration and K+/Mg2+
mechanism of Cisplatin and Carboplatin ototoxicity?
accumulates in the cochlear duct fluid…causing inflammatory response
also enters nerves and can kill the hair cells that aid hearing
three treatments for Cisplatin and Carboplatin ototoxicity?
uptake inhibitors for ear canal
anti inflammatories
anti oxidants
methotrexate mechanism and target stage as chemo drug
S phase…is a folate antagonist
What does methotrexate target and inhibit? what does this not allow to be made?
target dihydorfolate reductase DHFR
does not allow purine ring to be made or transformation of UMP into TMP (thymidine)
3 modes of methotrexate resistance
decreased uptake
increase DHFR production
DHFR mutations
methotrexates main toxicity
myelosuppression
methotrexate secondary toxicity
mucositis…inflammation and breakdown of GI mucosa
what is a risk with methotrexate?
if a patient has a 3rd space, pleural effusion of ascites, then methotrexate will enter this area and be stored until released later…can cause late toxicities
how is methotrexate cleared?
renally..why 3rd space is such an issue because it doesnt get cleared
what is a 3rd space?
pleural effusion or ascite
leucovorins effects on methotrexate?
it is a folate replacement and is actually only taken up by normal cells rescuing them from effects of methotrexate but still letting methotrexate screw with cancerous cells
name all six DNA alkylating non stage specific drugs?
cyclophosphamide ifosfamide Busulfan Carmustine Cisplatin Carboplatin
purine analogs (4)
mercaptopurine
azathioprine
Cladribine
Pentostatin
6-mercaptopurine toxicity
myelosuppression and T cell supression so more susceptible to bad infections like PJP
cytarabine MOA
fluorouracil MoA
pyrimidine analog
cytarabine toxicity
acute cerebellar neurotoxic
also see conjunctivitis because of being clearing in eyes
topoisomerase inhibitors (4)
irinonectan
topotecan
etoposide
teniposide
doxorubicin and daunorubicin MOA
and class
inserts into DNA and blocks unwinding for replication by making oxygen free radicals that damage DNA
anthracyclines
what do doxorubicin and daunorubicin need to work?
iron
irinotecan and topotecan toxicity
diarrhea…life threatening
etoposide toxicity
myelosuppression and secondary malignancy…AML
doxorubicin and daunorubicin toxicity
cardiac myocyte death
and extravasation injury
agent to prevent doxorubicin and daunorubicin toxicity
dexrazoxane…prevents it by picking up iron that the drugs need
Bleomycin MOA and stage
G2 phase and gets into helix and makes oxygen radicals
dactinomycin MOA and stage
inhibits transcription and G2
G2 drugs
bleomycin and dactinomycin
bleomycin toxiciity
pulmonary fibrosis
M phase drugs
vincristine, vinblastine, paclitaxel
vincristine, vinblastine and paclitaxel MOA
messes with microtubules so mitosis is not effective
vincristine and vinblastine toxicity
microtubules needed in nerves…can lead to peripheral neuropathy
name of drugs that target the Raf kinase inhibitor
vemurafenib and dabrafenib
HER2 inhibitors
cetuximab. erlotinib and trastuzumab
trastuzomab toxicity
cardio toxicity
unique allergy to cetuximab
from lone star tick bite…can see anaphylactic shock
VEGF inhibitor and what is this important for
Bevacizumab…kidney angiogenesis
what class of chemos is the most emetic agent?
alkylating agents, specifically the platins
what other treatment do you need to consider when giving chemo
you must have an anti emitic plan that is intensive
two drugs to treat anemia from chemo
epoietin alfa
darbepoietin alfa
what is risk of giving EPO for chemo treatment
tumor growth
two thrombocytopenia drugs that can cause lower thrombocytopenia due to an immune response
rTPO and PEG-rTPO
two thrombocytopenia drugs for chemo that do not have immune response
romiplosim
eltromobopag
name two drugs for neutropenia treatment with chemo
filgastrim (neulasta)
pegfilgastrim
these are artificial GCSFs
side effects of filgastrim and pegfilgastrim and how do we treat it
moderate to severe bone pain
claritin
what is a common oral side effect that causes eating problems of chemotherapy?
taste buds turnover every 10 days…dysgeusia
what happens to parietal gland with chemo and what drug to treat it?
leads to dry mouth…treat with pilocarpine (parasympathetic agonist)
how to treat neuropathy pain in the mandible/maxillary
make sure its not dental then manage with NSAIDs
