Cancer Chemotherapeutics Flashcards
What are two vinca-alkaloids?
Vincristine and vinblastine (-stine)
What is the mechanism for vinca-alkaloids?
They inhibit microtubule polymerization
What are two taxans?
Paclitaxel and docetaxel
What is the mechanism for taxans?
They inhibit microtubule depolymerization
What is similar between vinca-alkaloids and taxans?
They inhibit mitotic spindle function and are non-targeted chemotherapies
What are adverse effects of microtubule inhibitors?
They have general adverse effects seen in non-targeted therapies but some have specific AEs
- GI cells: Diarrhea, mucositis, nausea/vomiting
- BM cells: leukopenia, thrombocytopenia, anemia (all together= pancytopenia)
- Hair follicles: alopecia
What is a unique adverse effect found in paclitaxel?
Anaphylaxis
–> best to give corticosteroid and anti-histamine before using this to eliminate chance of allergic rxn
What are two unique adverse effects found in docetaxel?
Anaphylaxis and fluid retention
–> best to give corticosteroid and anti-histamine before
What are two unique adverse effects found in vincristine?
Extravasation (monitor for pain, swelling, poor blood return) and constipation (autonomic neuropathy so give laxative and stool softener)
What is a two unique adverse effects found in vinblastine?
Extravasation (monitor for pain, swelling, poor blood return) and myelotoxic
What chemotherapeutics cause peripheral neuropathy?
Paclitaxel and vincrestine
6- Mercaptopurine
MOA: Inhibits de novo purine synthesis
AE: Hepatotoxicity
DDI: Allopurinpol and febuxostat (uric acid reducer)
Methotrexate
MOA: inhibits de novo purine synthesis; also inhibits DHF-reductase (so inhibitor of thymidylate synthase and de novo purine synthase)
AEs: hepatotoxicity (BBW), bone marrow suppression (BBW); used with leucovorin to help limit toxic side effects
CIs: pregnancy (BBW)
5-fluoruracil
MOA: inhibits thymidylate synthase
AEs: hand-foot syndrome (skin toxicity)
Capecitabine
MOA: Oral prodrug of 5-fu
Hydroxyurea
MOA: inhibits ribonucleotide reductase
DNA intercalators: doxorubicin, doumorubicin, dactinomycin
MOA: intercalate into DNA and disrupt the progress of the replication fork (distorts the helix)
AEs: cardiomyopathy (prevention of this by using dexrazoxane which is an iron chelator), urine discoloration (red), and vesicant (can cause skin necrosis)
Cytarabine aka Ara-C
MOA: incorporates into DNA, blocks elongation
AEs: hepatotoxicity (BBW), BM suppression (BBW), cerebellar toxicity
TOPO inhibitors/DNA clearing agents: irinotecan, topotecan, etoposide
MOA: inhibit topoisomerase (freezes enzyme after cleavage before ligation) which causes DNA strand breaks
AEs: severe diarrhea (irinotecan is AChE inhibitor and can cause cholinergic symptoms–> use atropine before giving)
Bleomycin
MOA: produces ss/ds DNA breaks by a complex mechanism involving bleomycin, oxygen and ferrous iron
AEs: pulmonary fibrosis (major limitation) and hypersensitivity (anaphylactic reactions)
Cyclophosphamide
MOA: alkalates DNA and causes inter-strand crosslinks –> strand breaks and p55 helps cause apoptosis
AEs: hemorhagic cystitis (bleeding/bladder inflammation from formation of acrolein; prevent by excessive hydration and MESNA), secondary malignancies, gonadotoxic
Cisplatin
MOA: forms platinum adduct to cross link guanines and causes apoptosis
AEs: nephrotoxicity (b/c cleared by kidney) and can cause hypomagnesmia (monitor Mg, K, SCr; prevent via hydration and amifostin), ototoxicity
Oxaliplatin
MOA: platinum agent
AEs: less nephrotoxicity and less ototoxicity but neurotoxic –> can cause pharyngolaryngeal dysesthesia which can be caused/worsened by cold temp
EGFR-TKIs: erlotinib, gefitinib, brigatinib
MOA: blocks EGFR-Tyrosine kinase
AEs: rash (up to 75%), diarrhea, steven-johnson syndrome
HER-2/EGFR-TKI: Lapatinbib
MOA: blocks HER-2 (and EGFR) tyrosine kinase
AEs: cardiotoxic (decreases LVEF) and hepatotoxic
BCR-aBL TKI: imatinib, dasatinib, nilotinib
MOA: blocks BCR-Abl tyrosine kinase
AEs: GI, hepatotoxicity, QT prolongation (nilotinib specifically as there is a BBW)
BCR-aBL TKI: imatinib, dasatinib, nilotinib
MOA: blocks BCR-Abl tyrosine kinase
AEs: GI, hepatotoxicity, QT prolongation (nilotinib specifically as there is a BBW)
VEGFR TKI: Sunitinib
MOA: blocks VEGFR TK
AE: hepatotoxicity (BBW), hypertension, thromboembolism
Cetuximab
MOA: monoclonal antibody to EGFR
AEs: rash, GI issues, hypomagnesemia (EGFR targets TRMP6 so more Mg is reabsorbed)
Trastuzumab
MOA: monoclonal antibody against HER-2
AEs: cardiotoxic
Bevacizumab
MOA: monoclonal antibody to VEGFR
AEs: hypertension, thromboembolism, poor wound healing
