day 2 oncology Flashcards
MOA of epipodophyllotoxins
Act by inhibiting DNA topoisomerase II
prevents proper unwinding of DNA resulting in blockade of DNA synthesis and cell division
uses of epipodophyllotoxins
• Etoposide: lung cancer, germ cell cancer, gastric cancer
teniposide- pediatric leukemia***
2 types of epipodophyllotoxins
Etoposide
teniposide
3 adverse effects of epipodophyllotoxins
Myelosuppression
• Alopecia
• Hypotension
What are antitumor antibiotics?
Derived from microorganisms (bacteria)
compounds are produced and used by bacteria to compete with other microorganisms for resources
What are some examples of antitumor antibiotics?
Anthracyclines/Anthracenedione Mitomycin Doxorubicin Bleomycin Daunorubicin Epirubicin Idarubicin
MOA of anthracyclines
– Inhibit topoisomerase 2
generate free radicals
bind to DNA and intercalate DNA strands
DNA intercalation is what?
Drug binds to areas on both strands preventing DNA from being replicated
Free radical formation
Free radicals are very damaging to tissues by binding to metabolic products and disrupting cellular function
uses of anthracyclines
• Doxorubicin: breast CA, myeloma, leukemia, lymphoma
daunorubicin and idrarubicin- leukemia
epirubicin- breast, gastroesophageal CA
mitoxantrone- leukemia, lymphoma, prostate CA, multiple sclerosis
adverse effects of anthracyclines
• Myelosuppression • Alopecia • N/V • Mucositis • Vesicant if extravasated cardiotoxicity mitoxantrone- turns urine blue/ green doxo/ dauno/ ida/ epirubicin turn urine reddish/ orange
acute cardiotoxicity from anthracyclines
• Within 24-72 hours of admin
arrythmias, pericarditis, myocarditis
usually subclinical
chronic cardiotoxicity from anthracyclines
• Dose dependent
delayed by years
results in cardiomyopathy and heart failure
Cardiotoxicity of anthracycline
– 1 -2% risk for doxorubicin doses 500
Use of dexrazoxane
Reduces free radical formation in cardiac tissue
may reduce therapeutic effect of doxorubicin
Bleomycin MOA
Binds DNA and forms free radicals that destroy DNA and prevent DNA replication
Bleomycin uses?
lymphoma, germ cell tumor, head and neck cancer, SCC
What is a major concern with the use of bleomycin?
Pulmonary toxicity
symptoms include, cough, pnemonitis dyspnea
Pleural effusion is what?
• Pleural is fluid build up around the lung
prevents normal expansion upon inhalation
risk factors = age >70
supplemental oxygen
cumulative doses >400
underlying pulmonary disease
Tyrosine kinase inhibitors MOA
Inhibiting tyrosine kinases can target and block specific regulatory pathways and promote cancer cell death through apoptosis
What are the differences between the TKI’s?
– Target different TK that vary in level activity in different cancers
differ in binding affinity to their targets making some more potent inhibitors than other
some bind with less restricition
Resistance to TKI’s
Mutations in the amino acid sequence of tyrosine kinases could prevent the TKI from binding to the target site and make the drug inactive
Adverse effects of TKIs
– Rash – Myelosuppression – Fatigue – Fluid diarrhea CHF
Drug interactions of TKI’s
• Many metabolized by CYP450 enzyme system
enzyme inhibitors decrease metabolism and increase risk for side effects
enzyme inducers increase metabolism and decrease risk for side effects
reduced bioavailability with concomitant use of stomach acid reducers like PPI and H2 antagonists
possible MOA of immunomodulators?
– May alter tumor necrosis factor
may increase activity of NK cells and interferons
may promote apoptosis
immunomodulators MC used for what?
Mc used for multiple myeloma
in combo with dexamethazone
3 examples of immunomodulators
Thalidomide
Lenalidomide
Pomalidomide
adverse effects of immunomodulators
peripheral neuropathy thromboembolism fatigue rash dizziness myelosuppression
proteasomes inhibitors MOA
inhibit complexes of proteins that would otherwise breakdown unneeded or damaged proteins
proteasomes inhibitors used to treat what?
used in treatment for multiple myeloma
adverse effects of proteasome inhibitors
peripheral neuropathy neuralgia rash N/V/D heart failure pulm toxicity
monoclonal antibodies MOA
target specific proteions in cancer cells that block their standard function
(various sites on the surface of the cell)
how mAb kill tumor cells
could block receptors required for activating cell functions
could bind to free protein ligands looking to bind to receptors
could bind to receptors and cause apoptosis
could bind to receptors and cause antibody dependent cellular cytotoxicity
uses of mAb
rituximab- lymphoma
trastuzmab- HER2 breast cancer
panitumumab- colorectal cancer
cetuximab- colorectal, lung, head and neck CA
bevacizumab- colorectal, breast, lung, renal cell cancer
adverse effects of mAb
infusion related reactions
heart failure
hypomagnesemia
delayed wound healing
aspariginase MOA
breaks down asparagine to aspartate which will deprive the tumors of a vital amino acid leading to stress and apoptosis
forms of aspariginase
Ecoli
PEG
erwinia
use of aspariginase
part of combination chemo to treat ALL
adverse effects of aspariginase
hypersensitivity
pancreatitis
neurologic toxicity
clotting bleeding d/o
