Antineoplastic pharmacology Flashcards
Mechanism of action of 5-FU
Inhibit thymidylate synthetase
Drug that causes acute hemorrhagic cystitis
Cyclophosphamide
Drug that is cell cycle specific, acting specifically in mitotic phase
Paclitaxel
Cardiotoxicity limits total administration of
Adriamycin
Drug that doesn’t suppress bone marrow
Bleomycin
Kinase inhibitors
Imatinib (gleevec)
Nilotinib
Dasatinib
Antibody against EGFR-HER2 receptor
Trastuzuma (herceptin)
Antibody against VEGF
Bevacizumab (avastin)
Checkpoint inhibitors
Ipilimumab (yervoy)
Nivolumab (opdivo)
Inhibit angiogenesis by blockin VEGF and bFGF
Thalidomide
Lenalidomid
Proteosome inhibitors
Bortezamib (velcade)
Carfilzomib
Alkylating agents
Mechlorethamine Cyclophosphamide Busulfan Carmustin Cisplatin
Binds dsDNA containing guanosine, intercalates, and generates free radicals
Actinomycin D
Intercalated quinone redox center that binds Fe++ and oxidized to Fe+++ ->superoxides
Adriamycin
Glycopeptide that intercalates and generates free radicals
Bleomycin
Inhibitors of topoisomerase II
Etoposide
Teniposide
Inhibitor of topoisomerase I
Irinotecan
Imatinib (gleevec) is used frequently for
Ph+ CML and AML
Metabolism of imatinib (gleevec)
CYP3A4
Drugs that Compete with imatinib for CYP3A4 metabolism
Warfarin
Grapefruit juice
Drugs that induce CYP3A4 metabolism and affect imatinib administration
Phenytoin
St. John’s wort
Side effects of imatinib
Nvd Skin rxns Hepatotoxicity Htn Myelosuppression Edema CHF Musculoskeletal pain
Side effects of trastuzumab (herceptin)
Nvd Rigors Infusion rxns Cardiac dysfunction CHF Hypotension Edema
Uses for bevacizumab (avastin)
Colon cancer, vasculopathy
Checkpoint inhibitor that is an MAB against CTLA4 on T cells
Ipilimumab (yervoy)
*CTLA4 = cyctotoxic t lymphocyte associated protein 4
Uses for ipilimumab (yervoy)
Melanoma
NSCLC
Hodgkins lymphoma
Checkpoint inhibitor that is an MAB against PD-1 on some NK cells
Nivolumab (opdivo)
PD-1=programmed death receptor
Drug that can cause significant incidence of secondary leukemias
Etoposide and teniposide
Toxicity from checkpoint inhibitors prominently includes
Autoimmunity
Chimeric antigen receptor (CAR) T cell can be used for
Cancer and autoimmune
Subsets of treatment resistand cancers
Uses for angiogenesis inhibitors - thalidomide and lanalidomide
Causes direct growth arrest in multiple myeloma cells
Side effects of thalidomide
Teratogenic
Peripheral neuropathy
Side effects of lanalidomide
Teratogenic
Peripheral neuropathy
Neutropenia
Thromboembolism
Boron containing 26S proteasome inhibitor
Boretezamib
Bortezamib mechanism
Disregulates turnover of proteins mediating cell cycle (cyclins, p53)
ER stress -> apoptosis
Metabolism of bortezamib
CYP3A4
Uses of bortezamib (velcade)
Mutliple myeloma and mantle cell lymphoma
What is dose limiting toxicity of bortezamib (velcade)
Peripheral neuropathy
Drug that has extremely low therapeutic index ~1
Bortezamib (velcade)
Mechlorethamine mechanism
Alkylating agent
Form covalent adducts across DNA strands
Administration of mechlorethamine (alkylating agent)
Iv infusion near tumor site
Administration of cyclophosphamide (alkylating agent)
Oral -> wide distribution
Elimination of cyclophosphamide (alkylating agent)
Urine (active alkylator and metabolites)
Toxicities of cyclophosphamide
Classical toxicities + myocarditis and hemorrhagic cystitis
Use of cyclophosphamide (alkylating agent)
Hematogenous tumors
Administration of actinomycin d
IV
Elimination of actinomycin d
Bile and urine - unchanged
Uses of actinomycin d
Choriocarcinoma, wilms tumor, testicular tumors, karposis sarcoma
Administration and distribution of adriamycin
IV; wide except CNS
Elimination of adriamycin
Bile
Metabolism of adriamycin
Liver
Toxicities of adriamycin
Classical toxicities + adriamycin cardiotoxicity
Administration of bleomycin
Iv or IM
Use of bleomycin
Lymphoma, germ cell cancers, head/neck cancer
Folic acid analog
Methotrexate
Inhibits dihydrofolate reductase
Methotrexate
What cant be synthesiaed due to methotrexate
Thymidine
Tetrahydrofolate
Dose limiting toxicity of purine analogs (ie 6-MP)
Myelosuppression
6-MP blocks synthesis of
ATP and GTP
Metabolism of 6-MP (purine analog)
Tissue xanthine oxidase and thiopurine methyltransferase
6-MP has a reaction with
Allopurinol
5-FU inhibits
Thymidylate synthetase
Effects of 5-FU enhanced by
Leukovorin
Drug that can be used topically for basal cell carcinoma
5-FU
Toxicities of 5-FU
Classical toxicities + CNS (ataxia, confusion)
Drugs that bind to tubulin and disaggregate mitotic spindles -> metaphase arrest
Vinca alkaloids: vincristine, vinblastine
Drug that binds tubulin and stabilized microtubules -> metaphase arrest
Taxol (paclitaxel)
Estrogen agonist
Estradiol
Estrogen antagonist
Tamoxifen
Androgen agonist
Danazol
Androgen antagonist
Flutamide
GnRH agonist
Leuprolide
GnRH antagonist
Degarelix
Drugs that can be used for reversible chemical orchiectomy or oophorectomy
Leuprolide (GnRH agonist)
Degarelix (antagonist)
Aromatase inhibitors
Anastrazole, letrozole, vorozole
Mechanism of aromatase inhibitors
Prevent generation of estrogens from androgens
More effective than tamoxifen