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120 Cards in this Set
- Front
- Back
MOA of Heparin?
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Catalyzes the activation of antithrombin III, ↓ thrombin and Xa. Short half-life.
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Clinical use of Heparin?
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Immediate anticoagulation for pulmonary embolism, stroke, angina, MI, DVT. Used
during pregnancy (does not cross placenta). Follow PTT. |
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Toxicity of Heparin?
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Bleeding, thrombocytopenia, drug-drug interactions. For rapid reversal of
heparinization, use protamine sulfate (positively charged molecule that acts by binding negatively charged heparin). |
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Advantages of newer low MW heparins?
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Newer low-molecular-weight heparins (enoxaparin) act more on Xa, have better
bioavailability and 2–4 times longer half-life. Can be administered subcutaneously and without laboratory monitoring. Not easily reversible. |
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MOA of Warfarin (Coumadin)?
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Interferes with normal synthesis and γ-carboxylation of vitamin K–dependent clotting factors II, VII, IX, and X and protein C and S. Affects EXtrinsic pathway and ↑ PT.
Remember: "The EX-PaTriot went to WAR(farin)" |
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The 1/2 life of Warfarin is.......
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.....Long
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Clinical use of Warfarin?
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Chronic anticoagulation. Not used in pregnant women (because warfarin, unlike heparin, cancross the placenta). Follow PT values.
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Toxicity of Warfarin?
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Bleeding, teratogenic, drug-drug interactions.
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Heparin vs. Warfarin: structure?
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H: large anionic polymer, acidic
W: small lipid-soluble molecule |
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Heparin vs. Warfarin: route of administration?
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H: parenteral (IV, SC)
W: oral |
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Heparin vs. Warfarin: site of action?
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H: blood
W: liver |
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Heparin vs. Warfarin: onset of action?
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H: rapid (seconds)
W: slow, limited by half-lives of normal clotting factors |
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Heparin vs. Warfarin: MOA?
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H: activates antithrombin III, which decreases the action of IIa (thrombin) and Xa
W: impairs the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X (vitamin K antagonist) |
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Heparin vs. Warfarin: duration of action?
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H: acute (hours)
W: chronic (weeks to months) |
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Heparin vs. Warfarin: do they inhibit coagulation in vitro?
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H: yes
W: no |
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Heparin vs. Warfarin: treatment of acute overdose?
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H: protamine sulfate
W: IV vitamin K and fresh frozen plasma |
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Heparin vs. Warfarin: monitoring?
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H: PTT (intrinsic pathway)
W: PT (extrinsic pathway) |
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Heparin vs. Warfarin: crosses placenta?
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H: no
W: yes (teratogenic) |
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What drugs are thrombolytics? (4)
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-Streptokinase
-Urokinase -tPA (alteplase) -APSAC (anistreplase). |
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MOA of thrombolytics?
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Directly or indirectly aid conversion of plasminogen to plasmin, the major fibrinolytic enzyme, which cleaves thrombin and fibrin clots.
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Clinical use of thrombolytics? (2)
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Early MI
early ischemic stroke. |
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Toxicity of thrombolytics?
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Bleeding: Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diathesis, or severe hypertension. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis.
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p. 316 figure:
what converts fibrinogen to fibrin? |
thrombin
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what activates the breakdown of fibrinogen and fibrin?
what do they become? |
plasmin activates the breakdown
fibrinogen --> degradation products fibrin --> fibrin split products |
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What things activate the conversion of plasminogen to plasmin?
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-tPa
-urokinase -streptokinase (via an activator) -anistreplase |
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What things inhibit the conversion of plasminogen to plasmin?
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-antiactivators
-aminocaproic acid* |
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when endothelium is damaged, what platelet factor binds to the exposed collagen?
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GP1a
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what molecule binds to GP1b?
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vWF
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what platelet surface glycoprotein allows platelets to aggregate?
what molecule binds them together? |
GPIIb/IIIa
fibrinogen binds them |
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what drug is a monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets and thus prevent aggregation?
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Abciximab
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....see bottom right corner of figure on p.316...
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ok
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MOA of ASA?
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Acetylates and irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) to prevent conversion of arachidonic acid to prostaglandins. ↑ bleeding time. No effect on PT,
PTT. |
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Clinical use of ASA? (4)
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-antipyretic
-analgesic -anti-inflammatory -antiplatelet drug |
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Toxicity of ASA? (5)
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-gastric ulceration
-bleeding -hyperventilation -Reye's syndrome -tinnitus (CN VIII) |
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MOA of Clopidogrel and Ticlopidine?
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Inhibit platelet aggregation by irreversibly blocking ADP receptors. Inhibit fibrinogenbinding by preventing glycoprotein IIb/IIIa expression.
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Clinical use of Clopidogrel and Ticlopidine?
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Acute coronary syndrome; coronary stenting. ↓ incidence or recurrence of
thrombotic stroke. |
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Toxicity of Ticlopidine?
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neutropenia
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MOA of Abciximab?
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Monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated
platelets, preventing aggregation |
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Clinical use of Abciximab? (2)
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-acute coronary syndromes
-percutaneous transluminal coronary angioplasty |
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Toxicity of Abciximab? (2)
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-bleeding
-thrombocytopenia |
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CA drugs -- site of action: Methotrexate + 5-FU
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↓ thymidine synthesis
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CA drugs -- site of action: 6-MP
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↓ purine synthesis
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CA drugs -- site of action: Cytarabine???
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???
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CA drugs -- site of action: Alkylating agents + cisplatin?
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DNA cross-linkage
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CA drugs -- site of action: Dactinomycin + Doxorubicin
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DNA intercalation
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CA dugs -- site of action: Bleomycin?
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strand breakage + DNA intercalation
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CA dugs -- site of action: Etoposide?
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strand breakage
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CA dugs -- site of action: steroids???
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???
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CA dugs -- site of action: Tamoxifen?
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???
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CA dugs -- site of action: Vinca alkaloids?
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inhibit microtubule formation
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CA drugs -- site of action: Paclitaxel?
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inhibits microtubule disassembly
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What CA drugs are cell cycle specific?
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-antimetabolites (MTX, 5-FU, 6-MP)
-etoposide -bleomycin -vinca alkaloids |
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What drugs are cell cycle nonspecific?
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-alkylating agents
-antibiotics: dactinomycin, doxorubicin, bleomycin |
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What CA drugs inhibit the cell cycle at M phase?
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-vinca alkaloids and toxols
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Where do antimetabolites (anti-CA drugs) inhibit the cell cycle?
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S phase: DNA synthesis
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Where does Etoposide inhibit the cell cycle?
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S phase (DNA synthesis) and G2 (synthesis of components needed for mitosis)
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Where does Bleomycin inhibit the cell cycle?
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G2: synthesis of components needed for mitosis
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What happens during G1 phase of cell cycle?
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synthesis of components needed for DNA synthesis
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What happens during S phase of cell cycle?
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DNA synthesis
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What happens during G2 phase of cell cycle?
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synthesis of components needed for mitosis
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MOA of Methotrexate?
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S-phase-specific antimetabolite.
Folic acid analog that inhibits dihydrofolate reductase, resulting in ↓ dTMP and therefore ↓ DNA and protein synthesis. |
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Clinical use of Methotrexate? (8)
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Leukemias
lymphomas choriocarcinoma sarcomas Abortion ectopic pregnancy rheumatoid arthritis psoriasis |
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Toxicity of Methotrexate?
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Myelosuppression, which is reversible with leucovorin (folinic acid) “rescue.”
Macrovesicular fatty change in the liver. |
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MOA of 5-fluorouracil (5-FU)?
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S-phase-specific antimetabolite.
Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase, resulting in ↓ dTMP and same effects as MTX. |
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Clinical use of 5-fluorouracil?
Synergisitic with what? |
Colon cancer and other solid tumors, basal cell carcinoma (topical).
Synergy with MTX. |
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Toxicity of 5-fluorouracil? (2)
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Myelosuppression, which is NOT reversible with leucovorin.
Photosensitivity. |
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What drug inhibits thymidylate synthase?
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5-FU
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What is the action of thymidylate synthase?
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converts dUMP --> dTMP
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What drug inhibits DHF reductase?
What does this enzyme do? |
MTX
DHF reductase converts DHF --> THF |
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MOA of 6-mercaptopurine (6-MP)?
What activates it? |
Blocks de novo purine synthesis.
Activated by HGPRTase. |
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Clinical use of 6-MP?
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-leukemias
-lymphomas (not CLL or Hodgkin's) |
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Toxicity of 6-MP?
What enzyme metabolizes it and, thus, what drug should it not be used with? |
-bone marrow
-GI -liver Metabolized by xanthine oxidase; thus ↑ toxicity with allopurinol. |
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MOA of Cytarabine (ara-C)?
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inhibits DNA polymerase
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Clinical use of Cytarabine?
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AML
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toxicity of Cytarabine?
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-leukopenia
-thrombocytopenia -megaloblastic anemia |
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MOA of Cyclophosphamide and Ifosfamide?
How are these drugs activated? |
Alkylating agents; covalently x-link (interstrand) DNA at guanine N-7.
Require bioactivation by liver. |
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Clinical uses of Cyclophosphamide and Ifosfamide?
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-Non-Hodgkin’s lymphoma
-breast carcinomas -ovarian carcinomas Also immunosuppressants. |
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Toxicity of Cyclophophamide and Ifosfamide?
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-myelosuppression
-hemorrhagic cystitis (can be partially prevented with mesna) |
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MOA of Nitrosoureas?
-what's required? -do they enter the CNS? |
Alkylate DNA.
Require bioactivation. Cross blood-brain barrier → CNS. |
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Clinical use of Nitrosoureas?
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brain tumors (including glioblastoma multiforme)
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Toxicity of Nitrosoureas?
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CNS toxicity (dizziness, ataxia)
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MOA of Cisplatin and Carboplatin?
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Act like alkylating agents.
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Clinical uses of Cisplatin and Carboplatin? (4)
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-Testicular CA
-Bladder CA -Ovary CA -Lung CA |
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Toxicity of Cisplatin and Carboplatin?
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Nephrotoxicity and acoustic nerve damage.
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MOA of Busulfan?
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alkylates DNA
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clinical use of Busulfan?
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CML
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toxicity of Busulfan?
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-pulmonary fibrosis
-hyperpigmentation |
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MOA of Doxorubicin (Adriamycin) and Daunorubicin?
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Generate free radicals and noncovalently intercalate in DNA (creating breaks in DNA strand to ↓ replication).
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Clinical use of Doxorubicin (Adriamycin) and Daunorubicin?
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Part of the ABVD combination regimen for Hodgkin’s and for myelomas, sarcomas, and solid tumors (breast, ovary, lung).
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Toxicity of Doxorubicin (Adriamycin) and Daunorubicin?
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-cardiotoxicity
-also myelosuppression and marked alopecia -toxic extravasation |
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MOA of Dactinomycin (actinomycin D)?
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intercalates in DNA
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Clinical use of Dactinomycin (actinomycin D)?
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-Wilm's tumor
-Ewing's sarcoma -Rhabdomyosarcoma |
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Toxicity of Dactinomycin (actinomycin D)?
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-myelosuppression
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mnemonic for Dactinomycin?
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ACTinomycin D is used for childhood tumors (b/c children ACT out)
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MOA of Bleomycin?
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Induces formation of free radicals, which cause breaks in DNA strands.
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Clinical use of Bleomycin?
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-testicular cancer
-lymphomas (part of ABVD regimen for Hodgkin's) |
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Toxicity of Bleomycin?
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-pulmonary fibrosis
-skin changes, but minimal myelosuppression |
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MOA of Etoposide (VP-16)?
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G2-phase-specific agent that inhibits topoisomerase II and ↑ DNA degradation.
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Clinical use of Etoposide (VP-16)? (3)
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Small cell carcinoma of the lung and prostate
Testicular carcinoma. |
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Toxicity of Etoposide (VP-16)?
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-Myelosuppression
-GI irritation -Alopecia. |
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MOA of Prednisone?
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May trigger apoptosis. May even work on nondividing cells.
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Clinical use of Prednisone?
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Most commonly used glucocorticoid in cancer chemotherapy.
Used in CLL, Hodgkin’s lymphomas (part of the MOPP regimen). Also an immunosuppressant used in autoimmune diseases. |
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Toxicity of Predisone? (9)
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Cushing-like symptoms
immunosuppression cataracts acne osteoporosis hypertension peptic ulcers hyperglycemia psychosis |
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MOA of Tamoxifen and Raloxifene?
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Estrogen receptor mixed agonist/antagonists (“SERMs”) that block the binding of estrogen to estrogen receptor–positive cells.
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Clinical uses of Tamoxifen and Raloxifen? (2)
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Breast cancer.
Also useful to prevent osteoporosis. |
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Toxicity of Tamoxifen and Raloxifen?
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-Tamoxifen may ↑ the risk of endometrial carcinoma via partial agonist effects
-“hot flashes.” |
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MOA of Trastuzamab (Herceptin)?
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Monoclonal antibody against HER-2 (erb-B2).
Helps kill breast cancer cells that overexpress HER-2, possibly through antibody-dependent cytotoxicity. |
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Clinical use?
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metastatic breast CA
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Clinical use of Trastuzamab (Herceptin)?
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metastatic breast CA
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Toxicity of Trastuzamab (Herceptin)?
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cardiotoxicity
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MOA of Imatinib (Gleevec)?
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myoclonal antibody against the Philadelphia chromosome brc-abl tyrosine kinase
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Clinical uses of Imatinib (Gleevec)? (2)
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-CML
-GI stromal tumors |
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Toxicity of Imatinib (Gleevec)?
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fluid retention
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MOA of Vincristine and Vinblastine?
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M-phase-specific alkaloids that bind to tubulin and block polymerization of microtubules so that mitotic spindle cannot form.
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Clinical use of Vincristine and Vinblastine? (3)
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Part of the MOPP (Oncovin [vincristine]) regimen for lymphoma, Wilms’ tumor,
choriocarcinoma. |
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Toxicity of Vincristine and Vinblastine?
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Vincristine––neurotoxicity (areflexia, peripheral neuritis), paralytic ileus.
VinBLASTine BLASTs Bone marrow (suppression). |
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MOA of Paclitaxel and other taxols?
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M-phase-specific agents that bind to tubulin and hyperstabilize polymerized
microtubules so that mitotic spindle cannot break down (anaphase cannot occur). |
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Clinical use of Paclitaxel and other taxols?
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ovarian and breast carcinomas
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Toxicity of Paclitaxel and other taxols? (2)
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-myelosuppression
-hypersensitivity |
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What drugs are Nitrosoureas? (4)
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Carmustine
Lomustine Semustine Streptozocin |