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108 Cards in this Set
- Front
- Back
What is the mechanism of Heparin?
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Catalyzes the activation of AT3 which decreases Fx 2 and Xa
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Half life of Heparin:
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SHORT
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What is heparin used for clinically?
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IMMEDIATE anticoagulation for
-PE -Stroke -Angina -MI -DVT |
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When can heparin be used/why?
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Pregnancy - does not cross placenta
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How is Heparin therapy monitored?
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PTT
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3 toxic side effects of heparin:
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-Bleeding
-Thrombocytopenia (HIT) -Drug interactions |
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Antidote for rapid reversal of Heparin; mechanism?
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Protamine sulfate - pos charged molecule; binds highly neg charged Heparin
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What is a LMWH?
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Enoxaparin, Daltaparin
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How do the LMWH's act differently from Heparin?
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More action on Xa than Thrombin; better bioavailability and 2-4 times longer half life
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How can LMWH's be administered?
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Subcutaneously instead of only IV
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What is the good thing about better bioavailability and half life of LMWH's?
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Don't require lab monitoring with PTT
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What is Warfarin's clinical use?
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CHRONIC longterm anticoagulation
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When CAN'T Warfarin be used?
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Pregnancy - teratotenic
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Site of action of
-Heparin -Warfarin |
Heparin - blood
Warfarin - Liver |
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Onset of action of:
-Heparin -Warfarin |
Heparin - seconds
Warfarin - takes several days until the pre-existing clotting fxs are removed - half lives limit |
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4 Thrombolytic agents
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Streptokinase
Urokinase tPA APSAC |
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Mechanism of thrombolytics:
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Help convert Plasminogen to Plasmin to cleave Fibrin clots
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2 clinical uses of thrombolytic agents:
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-Early MI
-Early ischemic stroke |
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Toxicity of Thrombolytics:
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Bleeding
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What is the antidote for Thrombolytic TOXICITY?
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Aminocaproic acid - fibrinolysis inhibitor
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What is the rec on platelets for
-collagen -vWF -Fibrinogen -TxA2/ADP/5-HT |
Collagen is GP1a
vWF is GP1b Fibrinogen is GP2b3a Txa2/ADP/5HT all bind GP's |
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What 2 drugs inhibit platelet synthesis of thromboxane?
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Aspirin
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What drug blocks GP2b/3a to prevent Fibrinogen crosslinking the platelet plug?
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Abciximab
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What drugs irreversibly block ADP receptors on platelets?
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Clopidogrel and Ticlopidine
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What effect does blocking ADP receptors on Platelets have?
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It inhibits the expression of GP2b/3a hence no fibrinogen crosslinking!
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What are 2 clinical uses of Ticlopidine and Clopidogrel?
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Acute coronary syndorme
Cardiac stenting |
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What toxic side effect does Ticlopidine have?
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Neutropenia
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What are the 3 antimetabolite cancer drugs?
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-Methotrexate
-5-Fluorouracil -6-Mercaptopurine |
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How do MTX and 5-FU work?
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Synergistically
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What cell cycle phase are MTX and 5-FU both specific for?
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S-phase - DNA synthesis
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What is the mechanism of MTX?
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-Folate analog
-Inhibits Di-HF reductase, inhibits dTMP synth, DNA synth, and protein synthesis |
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What 4 cancers is MTX used for?
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-Lymphomas
-Leukemias -Choriocarcinoma -Sarcomas |
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What are 4 other clinical uses of Methotrexate?
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PEAR
-Psoriasis -Ectopic pregnancy -Abortion -Rheumatoid arthritis |
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What are 2 toxic side effects of MTX and how is one treated?
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-Macrovesicular Fatty Liver
-Myelosuppression - rescued with Leucovorin |
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What is the mechanism of 5-FU?
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-Pyrimidine analog; bioactivated to 5F-Dump; covalently complexes Folate which inhibits Thymidylate Synthase.
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And what is the effect of inhibiting thymidylate synthease?
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Inhibits dTMP synth, DNA, and protein synthesis.
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And what does giving MTX and 5-FU together allow for?
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Synergistic inhibition of the same biochemical pathway
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What are 3 cancers that 5-Fluorouracil is used for?
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-Colon cancers
-Other solid tumors -Cream for Basal cell carcinoma |
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What are 2 side effects of 5-Fluorouracil?
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-Photosensitivity
-Irreversible myelosuppression |
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What has to be given to 'rescue' the myelosuppression due to 5-FU?
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Thymidine
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What is the other antimetabolite?
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6-Mercaptopurine
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How is 6-MP activated and what is its effect?
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-Activated by HGPRTase
-Blocks de Novo Purine synthesis |
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What cancers can/can't 6-MP be used for treating?
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CAN treat Leukemia/Lymphoma
CAN'T treat CLL/Hodgkin lymphoma |
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What are 3 tissues that 6-MP has toxic effects on?
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-Bone marrow
-GI tract -Liver |
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What metabolizes 6-MP to its inactive form?
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Xanthine oxidase
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So what can prevent 6-MP metabolism?
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Allopurinol - careful!
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Drug for treating AML:
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Cytarabine; ara-C
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What is the mechanism of Cytarabine?
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INhibits DNA polymerase
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What are 3 toxic side effects of Cytarabine?
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-Leukopenia
-Thrombocytopenia -Megaloblastic anemia |
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What type of agents are Cyclophosphamide and Ifosfamide?
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Alkylating agents
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What is the mechanism of Cyclophosphamide and Ifosfamide? How are they activated?
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-X-link DNA (interstrand) at Guanine-7 - activated by liver bioactivation
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What are the 4 clinical uses of Cyclophosphamide and Ifosfamide?
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-NHL
-Breast cancer -Ovarian cancer -Immunosuppressant |
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What are 2 toxic side effects of Cyclophosphamide and Ifosfamide?
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-Myelosuppression
-Hemorrhagic cystitis |
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How can the Hemorrhagic cystitis caused by Cyclophosph and Ifosfamide be prevented?
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With MESNA
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What are the Nitrosoureas? 4
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-Carmustine
-Lomustine -Semustine -Streptozocin |
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What is the mechanism of the Nitrosoureas? What are they especially useful for?
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-Alkylate DNA
-Cross the BBB - so treat BRAIN TUMORS! |
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What brain tumor do the nitrosoureas like Carmustine especially treat?
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Glioblastoma multiforme
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What are the main toxic side effects of the Nitrosoureas?
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CNS - toxicity and Ataxia
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How do Cisplatin and Carboplatin work?
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LIKE alkylating agents
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What are the 4 cancers treated by Cisplatin and Carboplatin?
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OBLT
-Ovarian -Breast -Lung -Testicular |
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What are 2 toxic side effects of Cisplatin and Carboplatin?
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-Nephrotoxicity
-Acoustic nerve damage |
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What drug is used for treating CML?
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Busulfan
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What is the mechanism of Bulsulfan?
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Alkylates DNA
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What are 2 toxic side effects of Busulfan?
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-Pigmentation
-PULMONARY FIBROSIS |
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So what are the 4 alkylating agents?
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-Cyclophosphamide/Ifosfamide
-Nitrosoureas (Carmustine) -Cisplatin/Carboplatin -Busulfan |
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What is Doxorubicin aka?
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Adriamycin
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What is the mechanism of Doxorubicin and Daunorubicin? (3 steps)
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-Generate FREE RADICALS
-INTERCALATE DNA -CREATE BREAKS in DNA strand to inhibit replication |
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What is Adriamycin used for?
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-ABVD regimen - Hodgkin lymphoma
-Sarcomas -Myelomas -Other solid tumors (brst/ovary) |
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What are 3 toxic side effects of Adriamycin/doxorubicin/daunorubicin?
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-CARDIOtoxicity
-Marked Alopecia -Myelosuppression |
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What intercalator just intercalates and doesn't cause strand breaks?
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Dactinomycin
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What is Dactinomycin used for clinically?
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CHILDHOOD tumors
-Wilms tumor -Ewing's sarcoma -Rhabdomyosarcoma |
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What is the toxic side effect Dactinomycin can have?
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Myelosuppression
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What drug is the B in the ABVD regimen for Hodgkin lymphoma?
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Bleomycin
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What is Bleomycin's mechanism?
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Induces formation of free radicals - causes DNA strand breaks!
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What are 2 uses of Bleomycin then?
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-Hodgkin lymphoma
-Testicular cancer |
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What are 2 toxic effects of Bleomycin?
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-PULMONARY FIBROSIS (bab)
-Skin changes |
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What does Bleomycin cause MINIMALLY?
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Myelosuppression
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What cell cycle phase is Bleomycin specific for?
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G2
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What drug works on S and G2?
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Etoposide
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What is Etoposide's mechanism?
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-Inhibits Topoisomerase II
-Increases DNA degradation |
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What are 3 cancers Etoposide is used for?
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-SCC of lung
-SCC of prostate -Testicular cancer |
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SE's of Etoposide?
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Normal
-GI upset, myelosuppress, alopecia |
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What is the most commonly used Glucocorticoid in cancer therapy?
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PREDNISONE
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What is Prednisone's mechanism?
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Triggers Apoptosis
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What are 2 cancers Prednisone is used for treating?
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-CLL
-Hodgkin's lymphoma |
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What are 9 side effects of Prednisone?
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COACHH PIP
-Cushing's syndrome -Osteoporosis, Acne, Cataracts -Hypertension/Hyperglycemia -Peptic ulcers, Immunosuppress, Psychosis |
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What are the main drugs for treating Estrogen receptor pos breast cancer?
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Tamoxifen/Raloxifene
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How do Tamoxifen and Raloxifene work on the breast? Bone?
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Breast = Est antagonist
Bone = Est agonist! |
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So what are the 2 useful effects of Tamox/Raloxifene?
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-Slow Br cancer growth
-Slow osteoporosis! |
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What are 2 toxic side effects of Tamoxifen specifically?
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-Hot flashes
-May increase risk of endometrial carcinoma - agonist properties in the uterus |
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Why doesn't Raloxifene have this risk?
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It's an antagonist in the uterus
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What is Herceptin and what is it aka?
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Trastuzumab - anti Her-2 (erb-B2)
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What is Trastuzumab used for?
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HER-2 expressive Breast cancer
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What is a possible side effect of Trastuzumab?
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Cardiotoxicity
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What is Imatinib aka?
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Gleevac!
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What is Gleevac used for?
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Inhibition of the Ph' chromosome brc-abl fusion protein tyrosine kinase product
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So what 2 cancers are treated with Gleevac?
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-CML
-GI stromal tumors |
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What is a toxic side effect of Gleevac?
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Fluid retention
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What are the 'Vinca alkaloids'?
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Vincristine and Vinblastine
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What is the mechanism of Vincristine/blastine; what cell cycle phase are they specific for?
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-Bind tubulin, block MT polymerization - mitotic spindle can't form!
-M-phase specific! Mitotic |
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What are 3 clinical uses of Vincristine/blastine?
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-Wilm's tumor
-Lymphoma -Choriocarcinoma |
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What are 2 side effects of:
-Vincristine -Vinblastine |
Cristine = Neurotoxic/Paralytic ileus
Blastine = Bone marrow suppression |
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What is Paclitaxel?
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A Taxol!
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What is the mechanism of Paclitaxel and other Taxols?
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Bind tubulin and HYPERSTABILIZE polymerized MT's so the mitotic spindle can't BREAK DOWN!
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What cell cycle phase are the taxols specific for?
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M-phase - prevent progression to anaphase
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What are 2 cancers for which the Taxols/Paclitaxel are used?
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-Breast
-Ovarian |
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What are 2 side effects of the Taxols?
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-Myelosuppresion
-Hypersensitivity |
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What are the drugs that act on MIcrotubules?
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Maybe Taxes on Grease Vindicate Coalworkers!
-Mabendazole -Taxols (Paclitaxel) -Griseofulvin -Vincristine/blastine -Colchicine |