pharm heme module

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dtminhthu
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70175
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pharm heme module
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2011-03-04 12:21:43
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pharm heme module
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  1. Integrin complex on platelets that serotonin, TXA2, and ADP bind to to activate platelet
    GPIIb/GPIIIa
  2. Collagen binds to _____ to activate platelet
    GP 1a
  3. Platelet turnover in ____ days
    7-10
  4. Irreversible acetylation blockage
    Aspirin
  5. COX 1
    PGE2 (GI cytoprotection), TXA2 synthesis
  6. COX 2
    • synthesis of prostacyclin, PGE2 for inflammed tissue, no TXA2 synthesis.
    • Blockade leads to hypertension and thrombosis
  7. effect of low dose aspirin
    • Low-dose (81-325 mg/day) is more effective in preventing platelet initiated coagulation than higher doses
    • Decrease TXA2 and preserve ProstacyclinPlatelets cannot make more COX enzyme and are permanently inactive - no TXA2
  8. Aspirin side effects
    tinnitus, hearing loss, GI upset, bleeding defect
  9. Celecoxib (Celebrex)
    NSAID w/ more action at COX 2 blocker. Less GI bleed
  10. Inhibits thromboxane synthesis. Also prevents bronchoconstriction and vasoconstriction.
    Side effects: Vasodilation, hypotension, bleeding
    Dipyridamole
  11. ADP receptor (P2Y) blockers for anti clotting
    • Clopidogrel
    • Ticlopidine
    • Prasugrel
  12. Prodrug. Irreversible blockade of ADP receptor on platelets. Fibrinogen binding (platelet to platelet binding) is decreased by preventing glycoprotein IIb/IIIa expression on platelet surface.
    Clopidogrel
  13. Toxicity: GI upset, bleeding, rarely leucopenia
    Reduced effectiveness in patients with low CYP2C19 function
    Clopidogrel
  14. same MOA as Clopidogrel but may cause neutropenia/agranulocytosis, thrombotic thrombocytopenic purpura (TTP) and aplastic anemia
    Ticlopidine
  15. MOA of Ticlopidine
    Irreversible thromboxane synthesis inhibitor. Also prevents bronchoconstriction & vasoconstriction
  16. should be reserved for patients who are intolerant or allergic to aspirin
    It should be used when aspirin alone fails
    Adjunctive therapy with aspirin to reduce stent thrombosis
    Clopidogrel and Ticlopidine
  17. Risk of bleeding, Renal or hepatic impairment, Geriatric patients (increased sensitivity), Neutropenia, Thrombocytopenia, Thrombotic Thrombocytopenic Purpura (TTP)
    Ticlopidine
  18. Prodrug. Metabolized to active form via esterase, CYP3A4 and CYP2C19. Better metabolic activation than clopidogrel. More potent, faster acting, better consistency in platelet inhibition over time than clopidogrel
    Prasugrel
  19. Bleeding. Various cardiovascular. Various GI. Headache, dizziness, fatigue
    Discontinue at least 7 days prior to surgery
    Prasugrel
  20. Glycoprotein IIb/IIIa Inhibitors
    • Abciximab
    • Eptifibatide
    • Tirofiban
  21. Made from an immunoglobulin that binds platelet glycoprotein IIb/IIIa receptors. Abciximab has high affinity for the GP IIb/IIIa receptor, inhibits it. May last 24-48 hours. Used iv, in hospital, for angioplasty and stent placement to avoid ischemic events
    Abciximab
  22. incr risk of bleeding, esp GI hemorrhage. Can induce thrombocytopenia and may require platelet transfusion. Platelet counts can drop from 250,000-400,000 to zero
    Abciximab
  23. Reversibly binds to platelet surface glycoprotein IIb/IIIa. Short half life. Eptifibatide is always used together with aspirin or clopidogrel and heparin. Made from a protein found in snake venom.
    Eptifibatide
  24. Severe bleeding. Hypotension, heart failure, ventricular and atrial fibrillation. Anaphylaxis. Injectable, always used in hospital due to serious indications and side effects
    Eptifibatide
  25. Synthetic, glycoprotein IIb/IIIa inhibitor. Modified venom of the saw-scaled viper Echis carinatus, anticoagulant. IV. Rapid onset, short duration of action, reversed in 4-8 hours. Combined with heparin and aspirin. Used for unstable angina, myocardial infarction, coronary angioplasty
    Tirofiban
  26. Tirofiban Toxicity
    severe bleeding, Thrombocytopenia and thrombotic thrombocytopenic purpura
  27. Inactivate clotting factors
    Heparin
  28. iv anticoagulant. t1/2 1.5 hrs. High MW, powerful anticoagulant. Negatively charged, polar, will not easily cross membranes.. Short acting
    heparin
  29. Low molecular weight heparin. long acting
    • Enoxaparin
    • Dalteparin
    • Tinzaparin
  30. Synthetic heparin pentasaccharide binds specifically to the heparin binding site on Antithrombin III. Approved for DVT following hip and knee.
    Fondaparinux (Another Heparin)
  31. Heparin binds ____
    Antithrombin III
  32. Reverse heparin toxicity with...
    protamine sulfate
  33. benefit to lower molecular weight heparin
    less likely for thrombocytopenia, long acting
  34. Measure impact of Heparin in clotting
    • Partial Thromboplastin Time (PTT)
    • Activated Partial Thromboplastin Time (aPTT)
    • Partial refers to action of activator which depends on intrinsic activation, also.
  35. Oral anticoagulant. Blocks the synthesis of clotting factors. Benefit is delayed 1-3 days due to existing clotting factors in circulation with long t1/2
    Warfarin
  36. Blocks vit K epoxide reductase
    warfarin
  37. reversing warfarin toxicity
    replace vit K, clotting factor II and X
  38. Used to measure action of Warfarin. Blood is activated with prothrombin, Clotting Factor II. Clotting time is measured
    PT test / INR
  39. These drugs are derivatives or similar to Hirudin. Lepirudin is recombinant hirudin. Bivalirudin, Argatroban
    direct thrombin inhibitors. No thrombocytopenia
  40. Factor IIa
    thrombin
  41. source of Hirudin
    leech
  42. same action as streptokinase
    urokinase
  43. binds and activates plasminogen to produce plasmin (peptidase) action: destruction of fibrin
    Infused iv to increase survival during acute myocardial infarction
    streptokinase
  44. combination of plasminogen and streptokinase
    Anistreplase
  45. recombinant tissue Plasminogen Activators (tPA)
    Altelase, Duteplase and Reteplase
  46. reversing too much fibrinolysis
    Use Tranexamic acid or Aminocaproic acid to stop plasmin.
  47. for pregnant women, give ______ instead of warfarin
    heparin. warfarin may induce loss of pregnancy
  48. Iron form orally absorbed vs IV/IM
    Fe 2+ for oral. Fe 3+ for IV/IM only
  49. IV and IM iron toxicity
    Iron Dextran can cause vasodilation (headache, dizziness, flushing), fever, joint and muscle pain, urticaria and possibly anaphylaxis and death. The dextran is the hypersensitivity culprit.
  50. Iron-sucrose and Iron sodium gluconate
    IV/IM iron that is safer and less likely to cause anaphylaxis
  51. Oral iron therapy
    • 200-400 mg for 3-6 mo. All 2+ salts are useful Ferrous sulfate
    • Ferrous gluconate
    • Ferrous fumarate
  52. Nausea and GI distress, Abdominal Pain
    Black stool. Necrotizing gastroenteritis, bloody diarrhea, shock, lethargy, dyspnea, acidosis, coma, death.
    Acute iron toxicity
  53. treatment for acute iron toxicity
    Not activated charcoal (doesn’t bind iron), but whole bowel irrigation to purge pills and intravenous deferoxamine, a strong iron chelator.
  54. very effective in chelating ferric (3+) iron. Usually well tolerated by humans. It may scavenge iron from normal tissues.
    Injectable Deferoxamine
  55. Med that causes bone marrow toxicity. Anemia, neutropenia and sometimes as thrombocytopenia. Thymidine analog NRTI
    Zidovudine
  56. rHuEpo, Epoetin alfa
    Darbopoetin alfa, glycosylated long-acting
    Hematopoiesis - Erythropoietin
  57. filgrastim: daily injection
    Peg-filgrastim: covalent conjugation of filgrastim and polyethylene glycol. This preparation is long acting and can be injected once per chemo dose cycle.
    granulocyte colony stimulating factor
  58. Toxicity of G-CSF
    • Bone pain during the period of filgrastim or pegfilgrastim use.
    • Splenic rupture is possible, rare and serious.
  59. Has same effects as G-CSF on neutrophil proliferation and action. Additionally, it stimulates other cell lines to include red cells and platelets. Acts with Interleukin-2 to stimulate T-cell proliferation. Proinflammatory. Less effective than G-CSF in mobilizing peripheral blood stem cells.
    GM-CSF (granulocyte-monocyte). Sargramostin
  60. Toxicity of GM-CSF
    Fever, Malaise, Arthralgias and myalgias, Capillary leak syndrome, Peripheral edema, Pleural effusions, Pericardial effusions, Allergy is possible
  61. meds that can cause thrombocytopenia
    Heparin, quinidine, quinine, sulfa-containing antibiotics, some oral diabetes drugs, gold salts and rifampin
  62. Thrombopoietin synthesized in...
    human liver
  63. Oprelvekin
    • Transfusion may be adverse and ineffective. Oprelvekin (Interleukin 11) stimulates proliferation of platelets.
    • Adverse effects headache, dizzy, dyspnea (fluid), and arrhythmias.
  64. effect of phenytoin
    Blocks Dietary Folate absorption – Less N6-Methyl-THF
  65. low levels of Methionine in pregnancy can lead to ...
    neural tube defects
  66. Other effects of low Methionine
    • paresthesias and weakness relative to peripheral nerves, spasticity, ataxia and CNS dysfunctions.
    • Swelling neurodegeneration
  67. S-adenosyl-L-methionine effects
    Antidepressant. High homocysteine is same as low Methionine
  68. Injectable VitB12
    • Cyanocobalamin
    • Hydroxocobalamin is preferred
  69. Dose of folic acid needed
    1mg/d
  70. Sideroblastic anemia inducers
    • Toxins :(lead or zinc)
    • Drugs: INH, chloramphenicol, VitaminB6, or copper deficiency
  71. Drugs not to use for G6PD deficiency
    quinolones (anti-malarials, quinidine), sulfa antibiotics, and nitrofurantoin

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