ANTINEOPLASTIC_FINAL_CARDS.txt

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soren101
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ANTINEOPLASTIC_FINAL_CARDS.txt
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2012-04-17 14:14:39
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antineoplastic drugs ms2
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antineoplastic drugs final exam
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  1. EPOETIN ALFA
    Tx MYELOSUPPRESSION

    EPO REPLACEMENT

    IV OR SC

    • Tx
    • --FATIGUE
    • --SOB
  2. DARBEPOETIN
    Tx MYELOSUPPRESSION

    LIKE EPO ALFA BUT LONGER HALF LIFE
  3. OPRELVEKIN
    Tx THROMBOCYTOPENIA

    IL-11 = Megakaryocyte growth factor

    • Tx
    • Thrombocytopenia
    • (no platelets) → Hemorrhage
  4. FILGRASTIM
    MYELOSUPPRESSION

    • Granulocyte colony-stimulating
    • factor (G-CSF)

    • Tx
    • Leukopenia

    • i.e. Neutropenia
    • (Neutrophil count < 1000)

    • --infections
    • --fever

    • *Na dir neutrophils count during a cycle
    • of chemo is the most important value
  5. SARGRAMOSTIM
    MYELOSUPPRESSION

    Granulocyte –Macrophage colony-stimulating factor (GM-CSF)
  6. LEUCOVORIN
    Tx MYELOSUPPRESSION

    FOR BM "RESCUE" for pts taking methotrexate

    • nL CELLS TAKE UP LEUCOVORIN (FOLINIC ACID) TO SYNTH THF BUT TUMOR CELLS CAN'T
  7. MECHLORETHAMINE
    ALKYLATING AGENT

    • Polyfunctional alkylating agents: CCNS
    • Nitrogen mustards
  8. PROCARBAZINE
    ALKYLATING AGENT

    OTHER ALKYLATING AGENT: CCNS

    CNS DEPRESSION
  9. CYCLOPHOSPHAMIDE
    ALKYLATING AGENT

    • Polyfunctional alkylating agent: CCNS
    • Nitrogen mustard

    • Given p.o.
    • ---------------------------
    • ADVERSE / TOX

    Toxic to urinary bladder

    · Myelosuppression

    · Acrolein metabolite → non-hemorrhagic & hemorrhagic cystitis → hydration & freq urination nec to

    • ----Co-admin mesna (Na-2-mercaptoethane sulfate): free-radical scavenger binds acrolein metabolite → prevents GU damage (& rapidly cleared by kidneys)
    • ----“hematuria w/o bacteria”

    ALLOPURINOL prolongs t1/2 and inc toxicity
  10. NA-2-MERCAPTOETHANE
    SULFATE (MESNA)
    ALKYLATING AGENT

    TO PREVENT GU DAMAGE CAUSED BY CYCLOPHOSPHAMIDE

    • Co-admin mesna (Na-2-mercaptoethane sulfate):
    • --Free-radical scavenger binds acrolein metabolite
    • → prevents GU damage (& rapidly cleared by kidneys)
  11. BUSULFAN
    ALKYLATING AGENT

    Polyfunctional alkylating agent: CCNS

    Given p.o.

    • ADVERSE
    • --PULM FIBROSIS
    • --SKIN PIGMENTATION
    • --ADRENAL INSUFFICIENCY
  12. CARMUSTINE (BCNU)
    LOMUSTINE
    ALKYLATING AGENT

    Nitrosureas alkylating agent: CCNS

    crosses blood-brain barrier → Tx 1o CNS tumors

    CROSS-LINK DNA VIA ALKYLATION

    REQUIRES BIOACTIVATION
  13. WHICH TYPE OF RECEPTOR MUST BE PRESENT FOR Tx OF BREAST CANCER w GnRH ANALOGS LEUPROLIDE AND GOSERELIN?
    ESTROGEN RECEPTOS IN TUMOR TISSUE

    ACT ON PITUITARY TO INH RELEASE OF LH AND FSH

    DEC LH DECREASES ESTROGEN SYNTH BY OVARIES
  14. DACARBAZINE
    ALKYLATING AGENT: CCNS

    HODGKIN'S DISEASE = B CELL NEOPLASM

    "ABVD"

    • Adriamycin
    • (doxorubicin)

    Bleomycin

    Vinblastine

    Dacarbazine
  15. CISPLATIN
    ALKYLATING AGENT

    Platinum alkylating agents: CCNS

    Tx TESTICULAR AND LUNG CARCINOMAS

    FORMS INTRA AND INTERSTRAND CROSS LINKS AT N7 OF GUANINE VIA HYDROYSIS OF CHLORIDE GROUPS = INH DNA REP AND TRANSCRIPTION

    REPLACEMENT OF CHLORIDE w WATER FORMS ACTIVE DRUG

    S/E = NEPHROTOX WHICH IS DEC BY Cl- DIURESIS bc Cl- STABILIZES THE PLATIN COMPLEX

    RENAL TOX CAUSES LOSS OF Mg, Ca, K, AND PHOS

    CN VIII DAMAGE
  16. METHOTREXATE
    ANTIMETABOLITES

    CCS S-PHASE

    Tx leukemias and sarcomas

    MOA

    Structurally sim to folic acid. Given p.o. or intrathecal.

    • 1. Forms highly-active polyglutamate
    • compounds which persist in cancer cells.

    • 2. Reversibly inhb dihydrofolate
    • (DHF) reductase → prevents synth of tetrahydrofolate (THF)

    3. Lack of THF → decr synth of thymidylate, purine nucleotides & amino acids: Ser & Met.

    • ---------------------------------------------------
    • ADVERSE

    • 1. Myelosuppression
    • --Bone marrow can be rescued by treatment w/
    • leucovorin (folinic acid)
    • ---------------------------

    • RESISTANCE
    • --FOLATE TRANSPORTER --> DEC UPTAKE
    • --DHF REDUCTASE --> MUT TARGET
  17. 5-FLUOROURACIL
    ANTIMETABOLITES

    CCS S-PHASE

    Tx Colon cancer

    Pyrimidine (cytosine, uracil & thymine) analog

    1. 5-FU converted to F-dUMP irreversibly inhb thymidylate synthetase.

    2. Lack of thymidylate blocks DNA synth: “thymineless death”

    incorp into mRNA → prevents normal tsl of mRNA

    ORAL AND GI ULCERATION

    • RESISTANCE
    • --DIHYDROPYRAMIDINE --> INACTIVATION
    • --THYMIDYLATE SYNTHETASE --> MUT OF TARGET

    NO LEUCOVORIN RESCUE
  18. CYTARABINE (ARA-C)
    ANTIMETABOLITES

    CCS S-PHASE

    Pyrimidine analog

    Phosphorylated ara-CTP → Inhb DNA polymerase

    • Also phosphorylated ara-CTP incorporated into
    • DNA & RNA
    • --------------------
    • TOXIC TO CNS

    MEGALOBLASTOSIS


    • RESISTANCE
    • --CYTIDINE DEAMINASE--> INACTIVATES
  19. AZACITIDINE
    ANTIMETABOLITES -- ALTERS GENE EXPRESSION

    CCS S-PHASE

    Pyrimidine analog

    Inhb enz DNA methyltransferase

    METHYLATION TURNS OFF TUMOR SUPPRESSOR GENES
  20. 6-mercaptopurine
    ANTIMETABOLITES

    CCS S-PHASE

    • 2. Decr HGPRT actvy → 6-MP & 6-TG resistance
    • ---------------------------------------------
    • ADVERSE / TOX

    • 1. Xanthine oxidase degrades 6-MP.
    • ----Allopurinol (anti-gout drug) inhb xanthing oxidase → incr 6-MP toxicity → Must decr 6-MP dose.
    • ----6-TG not metab by xanth. oxids.

    2. Myelosuppression
  21. BLEOMYCIN
    ANTIBIOTIC DRUG

    CCS G2-PHASE

    peptide antibiotic

    1. Binds to DNA → forms O2 free radicals → single- & double-stranded breaks.

    2. Block DNA synth

    3. Fragmentation of DNA → Chromosomal abnormalities

    • 4. Cancer cells accumulate in G2
    • -----------------------------------------------
    • ADVERSE / TOX
    • 1. Pulmonary fibrosis*
    • ----Begin w/ dry cough, fine rales & difuse basilar infiltrates on CXR.

    • little bone marrow depression
  22. DRUG w ANTI-ESTROGENIC EFFECTS FOR Tx OF BREAST CANCER?
    TAMOXIFEN -- SERM

    or

    LETROZOLE -- AROMATASE INH

    • S/E TAMOXIFEN
    • --INC ENDOMETRIAL CANCER
    • --MENOPAUSAL SYMPTOMS
  23. DACTINOMYCIN
    ANTIBIOTIC DRUG aka ACTINOMYCIN D

    WILM's TUMOR

    1. Intercalates into ds-DNA btwn G≡C pairs.

    2. DNA-dependent RNA synth impaired → Block protein synth.

    3. (DNA replication is little affected)

    BONE MARROW SUPPRESSION
  24. DOXORUBICIN & DAUNORUBICIN
    ANTIBIOTIC DRUG aka HYDROXYDUNORUBICIN

    • CCNS
    • ·
    • Anthracycline
    • antibiotic drug

    1. Intercalates into DNA → blocks DNA & RNA synth

    4. Generate semiquinone & O2 free radicals (TOX)

    • 5. Cells die in G2
    • --------------------------------
    • ADVERSE / TOX

    • --♥Heart: Free radicals damage
    • --BONE MARROW DEPRESSION
    • --RED URINE -- NOT HEMATURIA
  25. ETOPOSIDE
    CCS LATE S-G2 PHASE

    1. Stabilize bond btwn Topo II & DNA

    2. Inhb Topo II → Double strand breaks remain

    • 3. DNA degraded
    • ---------------------------------------

    ADVERSE / TOX

    1. Dose-limiting Myelosuppression
  26. VINCRISTINE
    &
    VINCBLASTINE
    VINCA ALKALOIDS

    CCS: LATE G2-EARLY-M PHASE

    ON USMLE -- M PHASE

    MOA

    “Spindle poisons”

    • 3. Cells arrest in metaphase b/c mitotic
    • filaments cannot form.
    • -------------------------------------
    • ADVERSE

    • VINBLASTINE
    • --MYELOSUPPRESSION
    • --AREFLEXIA
    • --ALOPECIA

    • VINCRISTINE:
    • --AREFLEXIA
    • --PERIPH NEURITIS
    • --MUSC WEAKNESS
    • --PARALYTIC ILEUS
    • --ALOPECIA
  27. PACLITAXEL
    TAXANES

    CCS - M PHASE

    • MOA
    • “Spindle poisons”

    Tx ovarian and breast cancer

    1. Enhances polymerization of tubulin

    2. Promotes microtubule assembly

    Causes mitotic arrest b/c anaphase cannot occur.

    COLCHICINE, GRISEOFULVIN AND MEBENDAZOLE ALSO BLOCK MICROTUBULE FUNCTION

    • S/E
    • --BONE MARROW DEPRESSION
    • --PERIPH NEUROPATHY

    • RESISTANCE
    • --b-TUBILIN ISOTYPES --> MUT TARGET
  28. PREDNISONE
    Tx CHRONIC LYMPHOCYTIC LEUKEMIA & HODGKIN'S LYMPHOMA

    MOA - APOPTOSIS IN NON-DIVIDING CELLS

    • S/E
    • --IMMUNOSUPPRESSION
    • --ADRENAL SUPPRESSION
    • --PSYCHOSIS
  29. MOA OF RADIATION AND ALKYLATING AGENTS
    INC TUMOR CELL DEATH BY INC DOSE ANTIMETABOLITES

    INC TUMOR DEATH BY INC EXPOSURE TIME NOT DOSE
  30. HYDROXYUREA
    MISCELLANEOUS

    CCS - S PHASE

    • MOA
    • 1. Inhb ribonucleotide reductase

    2. Depletion of deoxynucleoside triphosphate → Prevents DNA synth

    • ----------------------------------
    • TOX
    • -MYELOSUPPRESSION
  31. IMATINIB
    MISCELLANEOUS

    • MOA
    • Blocks binding of ATP to Bcr-Abl tyrosine kinase → Inhb phosphorylation of kinase substrate (inhb oncogene product)

    Philidelphia (Ph) chromosome w/ t(9:22) → codes for fusion oncoprotein Bcr-Abl, a tyrosine kinase which is essential for prolif/survival of abnorm WBCs → chronic myelocytic (myelogenous) leukemia.
  32. BORTEZOMIB
    ALTERS GENE EXPRESSION

    ENHANCES APOPTOSIS -- Tx MULTIPLE MYELOMAS (PLASMA CELL CANCERS)

    MOA

    1. Inhb actvy of 26S proteasome

    2. Prevents degradation of IκB (inhibitor)

    3. Enhances apoptosis by preventing action of NF-κB (nuclear factor kappa: upreg DNA tsc, cell survival, inhb apoptosis)

    Treats multiple myeloma (plasma cell cancers).
  33. LEVAMISOLE
    IMMUNOMODULATING AGENT

    RESTORES DEPRESSED IMMUNE FUNC IN B CELLS, T CELLS, MONOCYTES AND MACROS

    POTENTIATES ANTINEOPLASTIC EFFECTS OF 5-FU IN Pts w COLON CANCER
  34. RITUXIMAB
    MONOCLONAL ANTIBODIES

    • MOA
    • Binds CD20 Ag expressed on all malignant B cell lymphocytes

    SLOWS TUMOR GROWTH AND DEPLETES THE PERIPH B-CELL POPULATION
  35. TRASTUZUMAB
    MONOCLONAL ANTIBODIES

    • MOA
    • · Blocks EGFR coded by HER2/neu (ErbB-2) gene

    • Treats breast cancer tumors (+) for HER2/neu
    • ----------------------------------

    ADVERSE TOX

    CARDIAC DYSFUNC, ESP IF Tx w DOXORUBICIN
  36. CETUXIMAB
    MONOCLONAL ANTIBODIES

    • MOA
    • · Blocks EGFR (HER1) in colorectal cancer
    • (60-75% pts express)

    Block cell prolif, survival & angiogenesis
  37. CELL CYCLE
    • G0
    • Differentiation. Resting phase.

    • G1 Synthesis of compounds needed to synthesize
    • DNA (18-30 hours)

    • S DNA replication & repair. Chromosomes double (16-20 hours)
    • --HYDROXYURIA
    • --5-FU
    • --6-MP, TP
    • --METHOTREXATE
    • --CYTARABINE

    • G2 Synthesis of molecules needed for mitosis
    • (2-10 hours)
    • --BLEOMYCIN
    • --ETOPOSIDE

    • M Mitosis (0.5-1 hour)
    • --VINCRISTINE/BLASTINE
    • --PACLITAXEL
  38. HEAT TOXICITY
    Anthracyclines = doxorubicin
  39. LUNG TOXICITY
    BLEOMYCIN
  40. KIDNEY TOX
    CISPLATIN
  41. URINARY BLADDER TOX
    CYCLOPHOSPHAMIDE
  42. CNS TOC
    CYTARABINE
  43. PNS TOX
    --Vincristine

    --Paclitaxel
  44. · EYE TOX
    5-FU
  45. LIVER TOX
    Asparaginase
  46. DERM TOX
    (skin/nails)
    Capecitabine
  47. Nitrosoureas alkylating agents: Cell Cycle Non-Specific (CCNS)
    Carmustine (BCNU)

    Lomustine (CCNU)

    Also act in G0 → Tx 1o tumors of CNS
  48. PLATINUM ALKYLATING AGENTS: Cell Cycle Non-Specific (CCNS)
    Cisplastin

    Carboplatin
  49. OTHER ALKYLATING AGENTS: CCNS
    Procarbazine
  50. Anthracycline antibiotic drugs: CCNS
    Doxorubicin aka Hydroxydaunorubicin
  51. ANTIBIOTIC DRUGS: CCNS
    Dactinomycin (Actinomycin D)
  52. GLUCOCORTICOIDS: CCNS
    PREDNISONE
  53. CCNS
    CELL CYCLE NON-SPECIFIC

    1) Can work at any step in the cell cycle, including G0

    2) Cells are more sensitive in late G1 & S phases b/c polynucleotides are more susceptible to alkylation in the unpaired state than in the helical form.

    3) Toxicity ~ expressed when cells enter S phase → Block progression through cell cycle.

    e.g. doxorubicin: intercalates into DNA → DNA strand scission (single & double strand breaks) via inhibition of topoisomerase II, (cells die in G2)
  54. G0-PHASE: CCS DRUGS
    • Corticosteroids suppress mitosis & cause
    • apoptosis of non-dividing cells

    G0 = 40% CELL CYCLE
  55. S-PHASE: CCS DRUGS
    Antimetabolites:

    • 1) 5-fluorouracil (5-FU)
    • 2) 6-mercaptopurine (6-MP)
    • 3) Methotrexate
    • 6) Cytarabine
    • 7) Hydroxyurea

    S-PHASE = 40% CELL CYCLE
  56. G2-PHASE: CCS DRUGS
    • 1. Bleomycin
    • 2. Etoposide
    • 3. Teniposide

    G2-PHASE = 18% CELL CYCLE
  57. LATE G2 / EARLY M-PHASE: CCS DRUGS
    1. Vincristine

    2. Vinblastine
  58. M-PHASE: CCS DRUGS
    • 1. Paclitaxel
    • 2. Docetaxel
    • 3. Vincristine
    • 4. Vinblastine

    2% OF CELL CYCLE
  59. CCS: CELL CYCLE SPECIFIC DRUGS
    1. Inhb cell division by acting during a specific cell cycle phase. Cells in sensitive phase are killed.

    2. CCS drugs most effective in hematologic cancers & tumors w/ a relatively large # of cells in the “growth fraction.”
  60. ALKYLATING AGENTS MOA
    • 1. Damage DNA via cross-linking (bifunctional drugs w/ 2 reactive groups)
    • --OR--
    • 2. Damage DNA via single-strand breaks (monofunctional drugs w/ 1 reactive group)

    Primary site of DNA alkylation is N7 position of Guanine. O6 also attacked.

    • Alkylation of DNA:
    • 1. Inhb synthesis of DNA, RNA & proteins

    • 2. Causes misreading of DNA
    • ------------------------------------------

    ADVERSE / TOX

    • 1. Myelosuppression & immunosuppression →
    • dose-limiting toxicity
  61. ALKYLATING AGENTS ADVERSE / TOX
    (Cyclophosphamide)
    ADVERSE / TOX

    1. Myelosuppression & immunosuppression → GRANULOCYTIC LEUKEMIA

    2. Sterile hemorrhagic cystitis. co-tx with Na-2-mercaptoethane sulfate (mesna) free-red scavenger


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