Chemo 2 Flashcards
topoisomerase I inhibitors - examples
*camptothecins:
-irinotecan
-topotecan
topoisomerase II inhibitors - examples
- anthracyclines:
-daunorubicin
-doxorubicin
-idarubicin
-epirubicin - epipodophyllotoxins
-etoposide - other: mitoxantrone
topoisomerase I inhibitors (camptothecans): MOA
*disrupt DNA strands by binding to the DNA-topoisomerase I complex and preventing the resealing of DNA (allows the cut in the DNA but does not allow it to be repaired)
recall: topoisomerase I relaxes supercoiled DNA by creating a single nick in the DNA and repairing it
topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins, mitoxantrone): MOA
*disrupt DNA strands by binding to the DNA-topoisomerase II complex and preventing the resealing of DNA (allows the cuts in the DNA but does not allow them to be repaired)
camptothecins - toxicities
*severe diarrhea:
-irinotecan > topotecan
*myelosuppression
anthracyclines - MOA
*topoisomerase II inhibitors (cuts both strands of one DNA double helix)
examples of anthracyclines
*daunorubicin
*doxorubicin
*idarubicin
*epirubicin
recall: anthracyclines are topo II inhibitors
anthracycline toxicities
*myelosuppression
*cardiotoxicity (dilated cardiomyopathy)
*extravasation injury:
-vesicant
-treat with dexrazoxane and cold compress
N/V
**red/orange urine discoloration
cardiotoxicity with anthracyclines (“-rubicins”)
*MOA: accumulation of oxygen-derived free radicals in the cardiac tissue, causing lipid, protein, and DNA damage
*acute: decreased contractility, pericarditis, myocarditis, arrythmia, elevation of biomarkers
*early-onset chronic progressive: tachycardia, ventricular dilation, exercise intolerance, pulmonary and venous congestion
*late-onset chronic progressive: ventricular dysfunction, conduction disturbances, arrythmias, CHF
prevention of cardiotoxicity associated with anthracyclines
*dexrazoxane: inhibit the iron-dependent free radical formation that can cause myocardial damage
*liposomal formulation:
-liposomal delivery system not as readily taken up by cardiac tissue, leading to decreased risk of cardiotoxicity
what drug is used IV to prevent cardiotoxicity associated with anthracyclines
dexrazoxane
mitoxantrone - overview
*similar mechanism to anthracyclines (topo II inhibitor)
*does NOT form free radicals: decreased risk of cardiotoxicity and extravasation
*blue-green urine discoloration
epipodophyllotoxins - overview
*example = etoposide
*MOA: inhibits topo II
*toxicities: myelosuppression, mucositis, hypotension
mitotic inhibitors - examples
- vinca alkaloids:
-vincristine
-vinblastine
-vinorelbine - taxanes
-paclitaxel
-docetaxel
-cabazitaxel - halichondrin B analog
-eribulin
vinca alkaloids - MOA
*prevent the assembly of tubulin dimers into microtubules → prevent mitotic spindle formation
*cells accumulate in mitosis and undergo apoptosis
vinca alkaloids - toxicities
*vinBLASTine (and vinorelbine) = blast the marrow = MYELOSUPPRESSION
*vinCRIStine = crisps the nerves = NEUROTOXICITY or peripheral neuropathy
note - FATAL if given intrathecally (into the CNS)
taxanes - MOA
*promote microtubule assembly
*interfere with microtubule disassembly
*stabilize microtubles → prevent mitotic spindle breakdown
taxanes - toxicities
*myelopsuppression
*mucositis
*peripheral neuropathy
*hypersensitivity reactions
eribulin - overview
*inhibits formation of mitotic spindles
*one of the mitotic inhibitors
*ADEs: neutropenia, alopecia, fatigue, peripheral neuropathy
proteasome inhibitors - examples
*bortezomib
*carilzomib
bortezomib - overview
*class: proteasome inhibitor
*MOA: REVERSIBLE binding of the proteasome → apoptosis
*toxicities: peripheral neuropathy, thrombocytopenia, neutropenia
note - subQ administration preferred due to less neurotoxicity
carfilzomib - overview
*class: proteasome inhibitor
*MOA: IRREVERSIBLE binding of the proteasome → apoptosis
*toxicities: cardiac arrest/CHF; pulmonary HTN/dyspnea, thrombocytopenia
traditional chemotherapy - drug classes
*platinums
*alkylating agents
*anthracycline
*topoisomerase inhibitors
*antitumor antibiotics
targeted chemotherapy - drug classes
*monoclonal antibodies
*small molecule inhibitors
rituximab - MOA
*chimeric antibody targeting CD20, most notably on B lymphocytes
rituximab - toxicity profile
*infusion reactions
*tumor lysis syndrome
*lymphopenia
*infection
EGFR/HER inhibitors
*monoclonal antibody:
1. trastuzamab - blocks HER2
-toxicities: reversible cardiotoxicity
2. cetuximab & panitumumab - HER1/EGFR
-toxicities: skin rash
*small molecule (tyrosine kinase inhibitor): erlotinib & gefitinib - targets HER1/EGFR tyrosine kinase
-toxicities: skin rash, diarrhea
EGFR/HER inhibitors - toxicity trends
*if target is EGFR1 (HER1): skin toxicities (rash)
*if target is HER2 (EGFR2): cardiac toxicities
BRAF inhibitors - MOA
disrupt downstream signaling that initiates from or proceeds to the BRAF domain
BRAF inhibitors - examples
-vemurafenib
-dabrafenib
-encorafenib
BRAF inhibitors - toxicities
*new primary malignancies
*BRAF (-) cancer
*uveitis/iritis
*rash, fatigue, nausea, diarrhea
VEGF inhibitors - MOA
*inhibit blood vessel formation
VEGF inhibitors - examples
*bevacizumab
VEGF inhibitors - toxicities
*thromboembolic bleeding events and HTN
tyrosine kinase inhibitors that target BCR-ABL - examples
*imatinib
*dasatinib
*nilotinib
tyrosine kinase inhibitors that target BCR-ABL - toxicities
*drug interactions
*GI toxicities
*myelosuppression
*elevated LFTs
*edema
*myalgias
