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44 Cards in this Set
- Front
- Back
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contact inhibition
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when a cell comes in contact with another cell type it doesn't grow any further
-cancer does not do this so can penetrate adjacent tissues and disseminate to distant sites |
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oncogenes
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-cause normal cells to become cancer cells
-produce oncogenic proteins and active various protein kinases and affect the cell cycle (G1 --> S) |
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neoplasia
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-uncontrolled cellular proliferation
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ideal antineoplastic drugs
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-eradicate cancer cells w/out harming normal cells
-present agents have sig toxicity b/c chemo drugs have difficulty distinguishing malignant from nml cells (esp rapidly dividing cells) -cancer cells divide and mutate rapidly and develop resistance; must use combo of many drugs |
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toxicities of chemo
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1. bone marrow suppression
2. GI- N/V 3. Stomatitis 4. Reproductive 5. Carcinogenic 6. Skin/hair 7. Neurotoxicity 8. Urologic/nephrotoxicity |
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cell cycle kinetics
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M- mitosis
G0- resting phase for cell differentiation G1-40% synthesize material for DNA replication S- 39% DNA replication G2- synthesize material for mitosis |
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Basic Chemo classes
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1. Alkylating agents
2. Antimetabolites 3. Plant Alkaloids 4. Biological agents 5. Abx 6. hormonal agents |
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5 basic mechanisms of action of chemo drugs 1-3
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1. Crosslinking DNA (inserts alkyl groups in b/t base pairs) so it cannot separate or replicate- leads to breaks in DNA strands
2. Mimic of fill in for DNA bases causing incorporation into DNA or RNA, block ezymes in biosynthetic pathays prevent repair of DNA or terminates chain formation during DNA synthesis; stops producing purines 3. Intercalating b/t bases pairs of DNA disrupting codons or producing free radicals that damage DNA |
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mechanisms of action 4-5
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4. Biological agents
-monoclonal ABs bind to tumor cell surface receptors and prevent/interfere with growth of tumor cell -block enzymes and prevent cell growth 5. Hormonal agents may antagonize receptors to prevent hormonally induced tumor growth |
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Alkylating Drugs (toxic to hematologic system)
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1. Mechlorethamine (nitrogen mustard)- IV
-N/V and myelosuppression, vesicant (be careful when preparing and administering drug, must be in vein b/c severly irritating) if extravasated can cause tissue damage -used IV in MOPP therapy for Hodgkins lymphoma 2. Cyclophosphamide (Cytoxan)- IV or PO -toxicity- myelosupression and hemorrhagic cystitis, N/V and alopecia, nadir (lowest WBC count) -must hydrate well (IV and PO); can give mesna to prevent hemorrahgic cystitis; ifosfamide is similar |
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Phenylalanine mustard (melphalan)
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-alkylating drug
-cross links DNA -toxicitiy- myelosuppression -used for multiple myeloma -can get a hypersensitivity rxn -carcinogenic ad teratogenic |
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Nitrosureas (carmustine, lomustine, semustine)
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-alkylating agents
-cross BBB and cross link DNA thru alkylation -used for brain tumors and other tumors, lymphomas -MYELOSUPRESSION (delayed effect), nephrotoxicity, acute N/V |
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Dacarbazine
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-aklylating
-causes marked N/V in > 90% pts, flulike syndrome and myelosuppresion |
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Platinum (Pt)- containing drugs
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-alkylating; Cisplatin and Carboplatin
-Cisplatin: sever N/V, dosel limiting renal dysfunction** and acoustic nerve dysfunction -Carboplatin less GI and nephro but more myelosuppression (esp plts- thrombocytopenia) |
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methotrexate
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-antimetabolite
-folic acid antagonist -folic acid is an essential cofactor for many enzymes that synthesize DNA and RNA; if cell is depleted it will have abnml DNA and abnml replication -IV and PO -toxicities --> oral and GI ulcerations (stomatitis), myelosuppression; leucovorin rescues nml cels -hepatotoxicity with chronic therapy (liver function tests must be done regularly) -alimtra- like methotrexate but also inhibits other enzymes |
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purine antagonists (inhibits adenine and guanine)
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-antimetabolites
-when activated, inhibits enzyme in purine ribonucleotide synthesis, decreases amts of guanine and may inorporate into DNA and RNA 1. 6-mercaptopurine (po) treats leukemias;tox: GI and hepatotoxicity (dose-related) 2. 6-thioguanine (po)- treats acture myelogenous leukemia (AML); causes myelosupression and hyperuricemia (high uric acid from breakdown of purines-seen with leukemia) |
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5-flurouracil (5-FU)
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-antimetabolites; pyrimidine antagonists
-undergoes metabolismand forms active metabolites which binds with thymidylate syhtase needed for thymine synthesis --> no thymine; imbalance DNA and RNA synthesis and cell death -IV and topical -toxicities: stomatitis and esophagopharyngitis with ulceration (mucositis), bone marrow suppresion; hand foot syndrome |
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Cytarabine
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-antimetabolitie; pyrimidein antagonist
-for AML -injectable agent that inhibits DNA polymerase and mimic cytosine incorporated into DNA causing defective DNA and chain termination (replication stops) -toxicities: severe myelosuppresion esp. neutrophils (neutropenia), N/V and occasionally mucositis -continuous infusion -teratogenic; contraind in preg |
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Gemzar (gemcitabine HCl)
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0antometabolite
-blocks enzymes needed to make the building blocks of DNA -incorporates into DNA (mimic) and stops DNA synthesis --> may trigger apoptosis -AE: myelosuppresion (dose-limiting), anemia, mild to moderate N/V and diarrhea, rash, fever |
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mitotic spindle
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-structure of cytoskeleton
-segregates chromosomes during cell division -formed by microtubules -chemo drugs can cause dysfunction of spindle |
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plant alkaloids
-vinca alkaloids |
-vesicants
1. Vincristine: IV, binds to tubulin and terminates microtubule (cytoskeleton) assemply --> halts mitosis -tox: alopecia and neuromuscular deficits* and injection site necrosis, ovairan dysfunction, loss of sperm, constipation 2. Vinblastine: prevents cytoskeleton formation, halts mitosis; treats lymphomas and other cancers -tox: LEUKOPENIA (WBC count nadir about 10 days later), NEUROLOGICAL (numbness and tingling, dec in DTRs, CN paralysis), alopecia |
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Etoposide and teniposide (podphyllotoxins)
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-plant alkaloid
-MOA: bind to and inhibits topoisomerase (allows for relaxation or coiling of DNA)- affect primarily DNA synthesis 1. Etoposide- IV and PO used for testicular and certain lung ca -tox: myelosppresion and N/V 2. Tenoposide: IV; used for ALL -AE: myelosuppression esp neutropenia, mucositis and N/V, hypersensitivity |
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Taxanes (paclitaxel, docetaxel)
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-plant alkaloids
-microtubuline poison --> disrupts cytoskeleton formation -tox: myelosuppresion, peripheral neuropathy in high doses, mucositis |
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Topotecan and irinotecan
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-plant alkaloids
-MOA: topoisomerase type 1 inhibitors 1. Topotecan: myelosuppression (all lines), N/V (premedicate with antiemetic drugs) 2. Irinotecan: late and severe diarrhea (24hrs-3wks), N/V, alopecia and less leukopenia but still myelosuppression |
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Anthracyclines (daunorubicin and doxorubicin)
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-abx
-MOA: intercalates with DNA causing breaks, generate DNA damaging free radicals; daunorubicin also acts as Topoiosmerase II inhibitor) -used for solid tumors, hematogenous cancers -tox: cardiotoxic at high cum doses; myelosuppression, alopecia, stomatitis; infusion rxns in up to 10% of pts (discontinue) |
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Dactinomycin
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-abx
-intercalates b/t DNA bases where it inhibits DNA dependent RNA polymerase (protein synthesis) -used for pediatric tumors -tox: anorexia, N/V, alopecia, mucositis and BM suppression (dose limiting) |
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Bleomycin
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-LUNG AND SKIN
-moa: reacts with O2 and iron to form radicals; binds to DNA and breaks backbone of DNA chain -used IV for germ cell tumors of testis and ovaries -tox: pulmonary fibrosis, cutaneous irritation, redness and ulceration; fever and chills |
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antiestrogens
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-selective estrogen receptor (ER) modulators (Tamoxifen) and newer drug, Fulvestrant (downregulates expression of ER)
-use: ER positive Breast cancer tx and prevention in high risk pts -AE: hot flashes, N/V. increased TE events, ?risk of endometrial ca |
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GnRH releasing analogs (leuprolide, goserelin)
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-GnRH analogs initially stimulate FSH and LH then inhibit (neg feedback) --> decreased testosterone (medical caustration) and decreased estrogens
-used for prostate ca and metastatic breast ca -AE: hot flashes, decreased bone mass, libido decline (esp in males) -new drug GnRH antagonist (dec testosterone): planaxis |
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antoandrogens
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-flutamide
-may be usefule for prostate ca -block effects of androgen -AE: dec sex drive, impotence, diarrhea, gynecomastia |
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aromatase inhibitors
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-inhibit aromatase, the enzyme that converts androgen to estrogen --> less estrogen)
-anastrozole and letrozole are used for breast ca (po) |
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Tretinoin
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-vitamin A derivative which binds to retinoic receptors and may cause terminal differentiation of leukemic cells
AE: night blindness, depression, pulmonary symptoms, chelitis |
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Immunomodulators-
immunotherapy (alpha IFN and IL2) |
-steps up the immune system response to killing cancer cells
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Rituxan (rituximab)
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-monoclonal ABs (target specific receptors)
-binds to the CD20 antigen on B lymphocytes, and the Fc domain recruits immune effector functions to medicate B-cell lysis (NHL) |
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Herceptin (trastuzumab)
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-recombinant DNA-dervied humanized monoclonal AB that selectively binds to the extracellular domain of the human epidermal growth factor receptor 2 protein
-metastatic breast cancer in cancers that overexpress HER 2 -IV |
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Erbitux (cetuximab)
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-for injection is a monoclonal AB for metastatic colorectal cancer
-binds to VEGF -blocks epidermal growth factor receptor |
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Bevcizumab (avastin)
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-binds to VEGF and prevents the interaction of VEGF to its receptors on the surface of endothelial cells
-metastatic colorectal cancer |
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Radioimmunotherapeutic agents
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-monoclonal ABs that are linked to a radioactive isotope that deliver cell specific cytotoxic radiation to malignant cells
-(Bexxar), Iodine 131 Tositumomab: directed against CD20; B cell NHL; provides more specific cytotoxic radiation -Zevalin consists of monclonal AB linked to the radiactive idotope yttrium-90 |
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Tyrosine Kinase
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-abnml enzymes (and receptors) which may be responsible for tumor growth, pathologic angiogenesis (new growth of blood vessels intotumors) , metastatic progression
-transfer phosphate groups; impt in signaling -impt in moving cell cycle foward |
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Imatinib (Gleevec)
-tyrosine kinase inhibitors |
-used for chronic myeloid leukemia for blast crisis and chronic phase after failure of interferon therapy
-MOA: inhibits the abnml protein tyrosine kinase --> inhibition of tumor cell growth -SE: edema, GI 1. Sprycel (dasatinib) is a tyrosine kinase inhibitor...similar to gleevec 2. sutent (sunitinib): another tyrosine kinase inhibitor 3. Tarceva: inhibits kinase associated w/epidermal growth factor receptor |
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Colony stimulating factors
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-bone marrow recovery during chemo
-growth factors for granulocytes and (macrophages) (filgrastim, pegfilgrastim) (neupogen, neulasta)- stim bone marrow to make more granulocytes (G-CSF) -given subcutaneously or IV -useful for pts with neutropenia associated with chemo -AE: bone pain and high levels of neutrophils with fever and chills |
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anemia secondary to cancer chemo
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-recombinant erythropoietin (subcutaneously given)-increases HgB and Hct
-Procrit, Epogen, 150 units/kg 3 times/wk for 8 wks -AE: HA, HTN, N/V and edema, injection site rxns -need to monitor Hct |
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chemo-induced N/V
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-Emetogenic chemo regimens require pre and post chemo antiemetic regimens with multiple drugs (at least 3)
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CINV (chemo induced N/V)
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1. Carmustine
2. Cisplatin 3. Cyclophosphamide 4. Dacarbazine 5. Dactinomycin 6. Lomustine 7. Mechlorethamine 8. Pentostatin 8. Streptozocin |
