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Hematologic Pharmacology
Hematologic Pharmacology
22
Pharmacology
Graduate
04/23/2011

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Cards

Term
Cyclophosphamide and Ifosfamide
Definition
Alkylating Agent

MECHANISM: Covalently Cross-links DNA at guanine. Require CYP-450 activation in liver.
USES: NHL, breast and Ovarian Cancer
SIDE EFFECTS: Toxic Metabolite is acrolein which causes hemorrhagic cystitis. Can be prevented by co-administration of mesna. Also myelosuppression + nausia.
Term
Nitrosureas (Carmustine, Lumustine, semustine, Streptozocin)
Definition
Alkylating Agent

MECHANISM: Require bioactivation. Can cross Blood-brain barrier because super hydrophobic.
USES: CNS tumors (esp. glioblastoma multiforme)
SIDE EFFECTS: CNS toxicity (ataxia, dizziness) and extreme nausia
Term
Cisplatin, Carboplatin
Definition
Alkylating Agent

MECHANISM: Cross link DNA strands, inhibit DNA replication,
USES: Testicular, bladder, ovarian, and lung cancer.
SIDE EFFECTS: NEPHROTOXICITY, neurotoxicity, ototoxicity. Extreme nausia.
Term
Busulfan
Definition
Alkylating Agent

MECHANISM: Alkylates DNA and interferes with function.
USES: CML
SIDE EFFECTS: Pulmonary Fibrosis, hyperpigmentation.
Term
Methotrexate
Definition
Antimetabolite

MECHANISM: Folic acid analog that inhibits dihydrofolate reductaces. Result: decreased DNA and protein synthesis. Specific for S phase (synthesis phase)
USES: Leukemias, lymphomas, sarcomas, choriocarcinoma. Also, abortion, ectopic pregnancy, rheumatoid arthritis, Crohn's, psoriasis

SIDE EFFECTS: Myelosuppression [leucovorin (folinic acid) reverses.] Also causes fatty changes in liver like ethanol/amiodarone
Term
6-Mercaptopurine (6-MP)
Definition
Antimetabolite

MECHANISM: Blocks purine synthesis. Must be activated by HGPRTase
USES: Leukemias, Lymphomas
SIDE EFFECTS: myelosuppression. Metabolized by xanthine oxidase, so toxicity when co-administerid with allopurinol (Xanthine Oxidase inhibitor)
Term
Cytarabine (ara-C)
Definition
Antimetabolite

MECHANISM: Pyrimidine antagonist, terminates chain elongation. Also inhibits DNA polymerase.
USES: AML
SIDE EFFECTS: Leukopenia, thrombocytopenia, megaloblastic anemia
Term
5-Flourouracil (5-FU)
Definition
Antimetabolite

MECHANISM: Pyrimidine analog. bioactivated to 5F-dUMP which binds folic acid which together inhibit thymidylate synthase. Result: inhibited nucleic acid synthesis. S-phase specific
USES: Colorectal cancer + other solid tumors. Used topically for skin basal cell carcinoma
SIDE EFFECTS: Myelosuppression, "hand-foot syndrome" (dermopathy after extended use)
Term
Etoposide, Doxorubicin, Irinotecan
Definition
Topoisomerase Inhibitor

MECHANISM: Inhibits topoisomerases (I or II) preventing DNA replication and inducing double stranded breaks
USES: Breast, thyroid, ovarian, and testicular cancer; lymphoma
SIDE EFFECTS: Doxorubicin has cardiac side effects (myopathy, failure, arrhythmia. Irinotecan cases severe diarrhea.
Term
Vincristine and Vinblastine
Definition
Targets Tubulin

MECHANISM: Interferes with tubulin binding. No mitotic spindle = no M phase
USES: Lymphomas, testicular cancer, small-cell lung cancer
SIDE EFFECTS: vi(N)cristine causes (N)eurotoxicity. vin(B)lastine causes (B)one marrow toxicity.
Term
Paclitaxel
Definition
Targets Tubulin

MECHANISM: Stabilizes Tubulin and prevents microtubule breakdown. M-phase cannot complete
USES: Ovarian, breast, non-small-cell lung, bldder, head and neck cancer.
SIDE EFFECTS: Acute hypersensitivy reaction, neurotoxicity
Term
Tamoxifen, Tetrozole, Raloxifene
Definition
Hormonal Agent

MECHANISM: Antiestrogen, block estrogen production or inhibit estrogen receptor on some cancer cells. Therefore decreases DNA synthesis.
USES: Estrogen-sensitive breast cancers. Raloxifen also stimulates bone density increase.
SIDE EFFECTS: Tamoxifen activates estrogen receptor on other tissue increasing endometrial cancer risk. All cause hot flashes/nausia
Term
Leuprolide and Goserelin
Definition
Hormonal Agent

MECHANISM: luteinizing hormone releasing hormone agonist. Decreases LH release, therefore inhibits testosterone/estrogen production
USES: Prostate cancer, breast cancer in premenopausal women
SIDE EFFECTS: Early exacerbation of prostate cancer
Term
Trastuzumab (Herceptin)
Definition
Targeted Molecular Theraputic

MECHANISM: Antibody against erb-B2 may help T-cell cytotoxicity against cancer cells with erb-B2
USES: breast cancers with erb-B2 (30%)
SIDE EFFECTS: Cardiotoxicity, esp. combined with doxorubicin
Term
Imatinib (Gleevec)
Definition
Targeted Molecular Theraputic

MECHANISM: inhibits BCR-ABL tyrosine kinase specific to CML
USES: CML
SIDE EFFECTS: mild
Term
Interferon-α
Definition
Endogenous Cytokine

MECHANISM: Enhances cell-mediated immunity against some cancers/viruses. Possibly upregulates antigen in tumor cell. May also have direct apoptotic activity.
USES: Hemangiomas, advanced melanoma, renal tumors (random: also hep C)
SIDE EFFECTS: Depression and flu symptoms
Term
Interleukin-2
Definition
Endogenous Cytokine

MECHANISM: Stimulates T-cell survival and activation. Enhances cell-mediated immunity against cancer cells.
USES: Kidney cancers and melanoma
SIDE EFFECTS: Capillary leak syndrome (hypotension, low vascular resistance, high cardiac output similar to septic shock)
Term
Anthracyclins (Doxorubicin, Daunorubicin, Adriamcyin)
Definition
Antibiotic

Generate free radicals and intercalate DNA causing breaks
USES: Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma
SIDE EFFECTS: myelosuppression
Term
Bleomycin
Definition
Antibiotic

MECHANISM: Induces free radical formation, which causes breaks in DNA
USES: Testicular cancer, lymphomas (pard of ABVD regimen)
SIDE EFFECTS: Pulmonary fibrosis, skin changes, minimal myelosuppression
Term
Hydroxyurea
Definition
MECHANISM: inhibits ribonucleotide reductase. Decreased DNA synthesis. S-phase specific
USES: Melanoma, CML, Sickle cell disease
SIDE EFFECTS: Bone Marrow Suppression, GI Upset
Term
Prednisone
Definition
Corticosteroid

MECHANISM: May trigger apoptosis. May work on nondividing cells.
USES: CLL, Hodgkins Lymphoma, immunosuppressant
SIDE EFFECTS: Chushing-like symptoms, immunosuppression, cataracts, acne, osteoperosis, hypertension, peptic uclers, hyperglycemia, psychosis
Term
6-thioguanine (6TG)
Definition
Antimetabolite
MECHANISM: Same as 6-MP
USES: AML
SIDE EFFECTS: Bone marrow depression, liver. Can be given with allopurinol
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