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68 Cards in this Set
- Front
- Back
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Alkylating agent properties and examples |
major target is DNA guanosine, adenosine, cytosine leads to cross linking, mispairing, depurination, and ring cleavage resistence via increase in P-glycoprotein, increase in competing nucleophiles, increase in DNA repair genes |
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Examples of nitrogen mustards |
mechlorethamine (IV), chlorambucil (oral), melphalan( (IV), cyclophosphamide (oral), ifosfamide (IV) |
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Side effects of cyclophospamide and ifosfamide
mechlorethamine |
Hemorrhagic cystitis prevented by mesna or N-acetyl-cysteine inactivates toxic metabolites (acrolein) in the urine
teratogenic |
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busulfan a. mechanisms b. toxicities c. indications
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a. cross links DNA low doses spares platelets and RBC but kills white blood cells
b. myelosupression and pulmonary toxicity
c. BBB penetration
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nitrosoureas a. examples b. mechanism c. side effects d. indications |
a. carmustine, lomustine b. alkylate and carbamoylate (destroy proteins) c. pulmonary toxicity d. brain tumors due to their lipophilic nature |
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dacarbazine a. mechanism b. indication |
a. metabolite acts as an alkylating agent, cell cycle non-specific b. melanoma and Hodgkin's disease, sarcoma |
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temozolomide a. mechanism b. indications c side effects |
a. metabolite acts as an alkylating agent, methylates DNA, cell cycle non-specific b. brain tumors, malignant gliomas c. reproductive organ inhibition, photosensitivity |
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bendamustine a. mechanism b. side effects |
a. alkylating agent and inhibits mitotic checkpoints and induces mitotic catastrophe b. hypersensativity, teratogenic |
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Platinum coordination complexes |
a. cisplatin, oxaliplatin, carboplatin b. guaninine crosslinking, DNA and RNA pol inhibition |
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Cisplatin and Oxaliplatin a. side effects b. indications |
a. Cis- N&V, renal tox, ototox, peripheral neuropathy, minor bone marrow supression oxa- moderate N&V, reversible peripheral neuropathy, mild bone marrow suppression b. Cis- testicular cancer, head and neck cancer, ovarian cancer, lung cancer, bladder cancer Oxa- colorectal cancer
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Carboplatin a. side effects b. indicaitons |
a. mild N&V, mild renal tox, mild ototox, peripheral neuropathy, major bone marrow suppression b. testicular cancer, head and neck cancer, ovarian cancer, lung cancer, bladder cancer |
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methotrexate a. mechanism b. toxicities c. indications |
a. folic acid analog, S phase specific, one carbon transfer, blocks dihydrofolate reductase, disrupts de novo synthesis of DNA - only one glutamic acid- cell adds more once inside b. renal toxicity (avoid with glucarpidase), liver w/ alcohol, radiation recall c. osteogenic sarcoma, IV high dose, requires leukovorin rescue with high doses
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pemetrexed a. mechanism b. side effects
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a. targets mainly thymidylate synthetase but also dihydrofolate reductase, glycinamide ribonucleotide formyl transferase GARFT and aminoimidazole carboxamide formyl transferase (AICARFT) where the latter two enzymes are involved in de novo purine biosynthesis b. usual side effects- requires B12 and folic acid synthesis |
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pralatrexate |
IV antifolate analog DHFR and thymidylate synthase |
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5-fluorouracil a. mechanism b. side effects c. indications d. properities |
a. IV, converted to FdUMP, inhibits thymidylate synthetase b. cerebellar ataxia, teratogenic, hand and foot syndrome c. lower doses- skin keratosis or psoriasis d. crosses BBB |
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5-fluorouracil derivatives |
capecitabine- less myelosuppression cytarabine- stomatitis gemcitabine- increased half life, decreased resistance |
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6 mercaptopurine a. mechanism b. side effects c. derivatives d. genetics |
hypoxanthine analog a. competes with hypoxanthine for HGPRT and its derivative 60TIMP competes with IMP for the formation of AMP and GMP inhibits purine biosynthesis, nucleotide interconversion and nucleic acid biosynthesis b. tumor lysis syndrome (allopurinol or rasburicase) c. azathioprine d. genetic test for 6-thiopurine methyltransferase (TPMT) |
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6 thioguanine a. mechanism
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a. 6-thioguanine damages DNA after incorporation into DNA and inhibits synthesis of AMP and GMP, no interaction with allopurinol, not degraded by xanthine oxidase
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fludarabine a. mechanism b. side effects |
a. converted to 2-fluoro-ara-ATP and inhibits DNa pol and ribonucleotide reductase b. rare neurological events
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cladribine a. mechanism b. side effects |
a. analog of deoxyadenosine with additional chlorine, activated by phosphorylation; once incorporates into DNA-inhibits synthesis and repair- induces breaks active against quiescent and dividing cells b. myelosuppression, nephrotox, neurotox |
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hydroxyurea a. mechanism b. indications c. side effects
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a. inhibits ribonucleotide reductase b. CML, solid tumors, sickle cell anemia, psoriasis c. skin hyperpigmentation, radiation sensitizer, radiation recall |
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vinca alkaloids a. examples b. mechanism c. side effects |
a. vinblastine, vincrisitine, vinorelbine b. disruption of microtubules for mitosis, M phase specific, formation of dimers c. neurotoxicity, bone marrow suppression, alopecia |
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taxanes a. mechanisms b. indications c. side effects d. examples
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from yew tree park a. causes the build up of the microtubules rather than allowing free tubulin dimers to form b. breast carcinomas, ovary, lung, head, neck c. radiation recall, cardiotoxic, fluid retention (doxetaxel) d. paclitaxel, docetaxel |
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etoposide |
epipodophyllotoxins from mandrake plant a. inhibit topoisomerase II repair enzymes |
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topotecan and irinotecan |
bind to topoisomerase I and create complexes irinotecan has severe diarrheal side effects
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anthracenes-anthracyclines |
doxorubicin, danorubicin, idarubicin, epirubicin
intercalates into DNA- RNA cannot use as a template, also binds top II
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doxorubicin |
IV discolors urine red radiation recall |
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bleomycin a. mechanism b. side effects c. indications |
a. binds to DNA forming complex with iron to break DNA b. pulmonary fibrosis, pulmonary tox, anaphylaxis, fever, hyperkeratosis-blistering, GI c. testicular cancer |
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L-asparaginase, pegasaragase a. mechanism b. indications c. side effects |
a. limits protein synthesis in cancer cells requiring large amounts of asparagine for growth b. ALL c. lack of tox to bone marrow, GI, no hair loss has HSR, CNS tox, fever, liver and kidney damage, pancreatits, excessive NH3, coag deficiencies |
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arsenic trioxide a. mechanism b. indications c. side effects |
a. induces differentiation of promyelocytic leukemia b. APL refractory to tretinoin c. QT prolong |
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tretinoin a. mechanism b. indication c. side effects |
a. induces differentiation of acute promyelocytic cells b. APL c. Vit a toxicity, fever, skin dryness, CNS tox, teratogenic |
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Properties of hormonal agents |
may lack bone marrow suppression, stomatitis, alopecia, severe N&V used for hormone-sensitive tumors; primarily breast and prostate least toxic of all anticancer drugs and actions are selective through specific hormone receptors |
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prednisone, dexamethasone |
glucocorticoid receptor specific hormones a. binds to glucocorticoid receptors; complex then binds to DNA sequences, glucocorticoid response elements, which repress or activate transcription for specific genes. Causes apoptosis to lymphocytes or a lymphocytolytic effects b. can suppress chemo induced N&V, pain reduction, reduction of cerebellar edema c. moon faces, obesity d. must withdraw meds slowly to prevent adrenal insufficiency |
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EGFR tyrosine kinase inhibitors |
cause apoptosis and inhibit cell proliferation cetuximab- severe infusion reactions, acne-like rash, intersitial lung disease panitumumab- full human antibody erlotinib- interstitial lung disease, GI perforation, teratogenic |
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BCR-ABL tyrosine kinase inhibitors |
imantinib- thrombocytopenia nilotinib- QT prolongation* dasatinib- QT prolongation* *used for imantinib resistant |
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RAS/MAP Kinase pathway inhibitors |
inhibits phosphorylation and activation of various cell suface and intracellular tyrosine kinases (VEGF) receptor sorafenib sunitinib pazopanib vandetanib |
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vemurafenib a. mechanism b. indications c. side effects |
a. inhibitor of BRAF mustated forms of BRAF serine threonine kinase b. metastatic melanoma c. QT prolongation |
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m TOR kinase inhibitors a. mechanism b. examples c. side effects |
a. protein kinase that helps regulate cell growth, proliferation, and survival. Inhibition leads to GI arrest and apoptosis b. temsirolimus, everolimus c. hypersensitivity, immunosuppression, hyperglycemia, hyperlipidemia, hypertriglyceridemia |
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Anaplastic lymphoma kinase inhibitor |
crizotinib inhibits anaplastic lymphoma kinase positive cancer cells QT prolongation, GI, edema, visual disturbances |
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Proteasome inhibitors |
a. bortezomib and carfilzomib b. small molecule inhibits proteasome c. multiple myeloma, mantle cell lymphoma d. GI effects, bone marrow suppression, constipation, peripheral neuropathy, cardiotoxicity and fever |
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bevacizumab a. mechanism b. indications c. side effects |
a. suppresses formation of new blood vessels, binds to VEGF b. metastatic cancer of the colon or rectum (5-FU), nonsquamous non-small cell lung cancer (carboplatin and paclitaxel) c. GI perf, disrupted wound feeling, kidney damage, HTN, thromboembolism |
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thalidomide a. mechanism b. indications c. side effects |
a. inhibits FGF (fibroblast growth factor), VEGF, and TNF alpha but costimulates T cells b. multiple myeloma c. powerful teratogen |
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lenalidomide a. mechanism b. indications c. side effects |
a. suppresses angiogenesis, inhibition of TNF and costimulation of T cells b. multiple myeloma c. teratogenic, thrombocytopenia, thromboembolism |
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rituximab a. mechanism b. indications c. side effects |
a. binds to CD-20 inducing apoptosis and immune attack against B cells b. B cell non-Hodgkin lymphoma, CLL c. infusion related events, cardiac issues, lymphopenia, reactivation of HBV infections, immunosuppression |
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ibritumomab a. mechanism b. indicaitons |
a. anti-CD20 linked with the chelator tiuxetan, B cells killed by radiation b. non Hodgkin's lymphoma |
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tositumomab/I-tositumomab a. mechanism b. indications c. side effects |
a. anti-CD20 linked with radioactive 131I b. rituximab refractory non-Hod lymphoma c. severe BM suppression , HSR, hypothyroidism, contraindicated for pregnancy |
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ofatumumab a. mechanism b. indications c. side effects |
CD20 B-CLL, w/ failed alkylating agent and fludarabine therapy infusion related reactions |
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ipilimumab a. mechanism b. indications c. side effects |
a. blocks CTLA-4 on T cells b. metastatic melanoma, often used with dacarbazine c. immune mediated conditions |
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brentuximab vedotin a. mechanism b. indication c. side effects |
a. anti CD30, linked to a MT disrupting agent MMAE and a protease linker b. Hodgkin's lymphoma after failure of autologous stem cell transplant c. peripheral neuropathy, neutropenia, infusion reactions |
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vorinostat, romidepsin a. mechanism b. indications c. side effects |
a. histone deacetylase inhibitor increasing acetylation of histones and regulatory proteins in the cell nucleus and control DNA transcription. Acetylation increases gene transcription leading to cell-cycle arrest and apop b. cutaneous T cell lymphoma c. thrombocytopenia, pulmonary embolism, cardiotoxicity |
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IFN alpha 2a/b a. mechanism b. indications c. side effects |
a. bind to cell surface receptors causing gene expressions that result in enhancement of host immune responses and direct antiproliferative effects on cancer cells b. CML, HCL, malignant melanoma, AIDS-related Kaposi's sarcoma, non-Hodgkin's lymphoma, hep C and B c. flu like symptoms |
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aldesleukin a. mechanism b. indications c. side effects |
a. large glycoproteins, human IL-2 b. metastatic renal cell cancer and melanoma c. significant toxicity, hypotension (capillary leak syndrome), anemia, sinus tachycardia, pulmonary congestion |
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tamoxifen |
non-steroidal antiestrogen receptor blocker with both agonist and antagonist properties antagonist and agonist estrogen side effects: hot flashes, nausea, thrombophlebitis, endometrial cancer, maintain bone density |
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toremifene |
analog of tamoxifen anti-estrogen receptor, postmenopausal women |
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fulvestrant |
derivative of tamoxifen no estrogen agonist side effects ex. no thrombophlebitis |
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raloxifene |
prophylactic for post-menopausal women |
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aromatase inhibitors |
anastrozole (non-steroidal) letrozole (non-steroidal) exmestane (steroidal) ER positive breast cancers interfere with the production of estrogen from androgens
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trastuzumab |
monoclonal anti Her-2-nu side effects- cardiotoxicity no bone marrow suppression or allopecia
can be combined with microtubule inhibitory drug DM1 |
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lapatinib |
intracellular interference with EGFR; Her-2-nu less cardiotoxicity, but bone marrow suppression given with capecitabine |
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ixabepilone |
binds beta tubulin subunits; M cycle specific used in resistence breast cancers to anthrcyclines and taxanes myelosuppression, peripheral neuropathy
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eribulen mesylate |
MT inhibitor; marine sponge |
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cabazitaxel |
MT inhibitor taxane hormone refractory prostate cancer |
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bicalutamide flutamide nilutamide |
androgen receptor blocker metastatic prostate cancer side effects: hot flashes, gynecomastia, vomiting, diarrhea, hepatotoxicity |
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Gonadotropin releasing hormone agonist |
suppresses androgen production in the testes does not decrease adrenal androgens feedback loop inhibition leuprolide goserelin triptorelin histrelin |
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Gonadotropin releasing hormone antagonist |
degarelix blocks GnRH receptors in pituitary and decreases release of LH and FSH no testosterone production
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estramustine |
non-hormonal prostate cancer drugs conjugate of estradiol phosphate and nitrogen mustard inhibits MT structure hormone refractory, metastatic prostate cancer |
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sipuleucel-T |
biological response modifier active cellular immunotherapies APCs from patient are fused with a recombinant protein made of PCP fused to PAP-GM-CSF to enhance cell activation
asymptomatic or minimally symptomatic, metastatic, adrogen-independent prostate cancer |
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abiraterone acetate |
inhibits 17 alpha hydroxylase; enzyme required for androgen biosynthesis use with prednisone to balance mineralcorticoids metastatic castration resistant prostate cancer, resistant to docetaxel pregnancy category X |
