Learning Objectives (Midterm)

Learning Objectives (Midterm) - A nticoagulants: - Heparin...

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Anticoagulants: - Heparin o UFH MOA: binds AT, induces conformational change to bind (and inhibit ) thrombin and Xa by 1000-fold Neutralizes IXa , XIa , XIIa (little against VIIa) Indications: DVT, PE, MI, cerebrovascular accident (CVA) or stroke Note: no fibrinolytic activity, no lysis of established thrombi Key ADEs: HIT Monitoring: aPTT, PT, ACT Reversal: Protamine o LMWH MOA: same as UFH but less ability to bind thrombin (IIa) Indications: Tx DVT, prevent DVT/PE Advantages: more predictable dose response, longer duration of action Note: routine monitoring with aPTT not useful - Fondaparinux o MOA: Xa-inhibitor via accelerated ATIII neutralization of thrombin, Xa overall result = inhibition of prothrombin thrombin conversion o Indications: prophylactic DVT, PE following THA o No reversals - Direct Thrombin Inhibitors (lepirudin, bivalrudin, argatroban) o MOA: direct thrombin inhibition (can inhibit both fibrin-bound and circulating thrombin; c.f. heparin which can only inhibit o Indications: HIT - Warfarin 1
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o MOA: inhibit Vit K e poxide reductas e activity (dec Vit K factors II, VII, IX, X, C, S) o Measure: PTT, INR (most sens to VII) o No drug excreted unchang ed in urine o (Complex patients) 4 D’s: diet, dos e, drugs, diseas e o Risk of loading dose: m ay lead to warfarin induced necrosis if already Factor C d eficient o Alcohol Chronic: induce P450 less warfarin av ailable (ne ed to inc dos e) Acute: substantial inc in PT/INR excessive anticoagulation – high risk of hemorrhage - New Drugs o Dabigatran (DTI) o Rivaroxaban (direct Xa inhibitor) Erythropoietin Therapy: 1. Describe the mechanism by which erythropoietin regulates gene expression. Production inversely related to tissue oxygenation (i.e. low O 2 = high EPO) Uses Jak-Stat pathway to maintain and expand terminal maturation of erythroid progenitor cells – prevent apoptosis Cause premature release of marrow reticulocytes 2. Discuss the structural features of erythropoietin. 64 kDa glycoprotein, 165 AA, 40% carbo Made mostly in kidney 3. Describe the factors that control erythropoietin production. Ex: Absence of O 2 Bind HIF-alpha, which will bind HIF-beta to induce gene transcription (inc EPO) 2
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Ex 2: O 2 present HIF-alpha is proteolytically destroyed via ubiquitin tagging 4. Describe the clinical applications for ESA therapy. Anemia correction in dialysis patients Avoidance of transfusions Reversal of Fe overload Reduction in LVH, LVMI Improve QoL Chemo-induced Anemia Black Box Warning: Avoid in pts with Hgb >10g/dL Only given to pts with anemia due to chemo Not given for intent-to-cure (where prolonged survival anticipated) Antineoplastic Agents: 1. Discuss the etiology of cancer. 2.
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Learning Objectives (Midterm) - A nticoagulants: - Heparin...

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