questions 9

Anticoagulants

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Topic updated on 11/12/17 9:15am

Overview

  • Anticoagulants decrease the formation of fibrin clots
    • heparin
    • warfarin (coumadin)
    • bivalirudin
Heparin
  • Mechanism
    • catalyzes the binding of antithrombin III to multiple clotting factors  
    • inactivates several factors
      • IIa (thrombin)
      • Xa
      • IXa
      • XIa
      • XIIa
  • Clinical use
    • immediate anticoagulation
      • pulmonary embolism
      • acute coronary syndrome
      • stroke
      • MI
      • DVT
      • DIC
    • during pregnancy
      • does not cross placenta
  • Toxicity
    • bleeding
    • osteoporosis
    • heparin-induced thrombocytopenia (HIT)
      • heparin binds to platelet factor IV
      • antibodies bind to and activate platelets
      • leads to hypercoagulable state and thrombocytopenia
    • hypersensitivity
  • Pharmacology
    • IV delivery only for therapeutic anticoagulation
    • short half-life (2h)
    • large, water-soluble polysaccharide
    • low-molecular-weight heparins (e.g. enoxaparin) have advantages of
      • longer half-lives (2-4x)
      • less thrombocytopenia
      • enhanced activity against factor Xa
      • administered subcutaneously without laboratory (PTT) monitoring
      • not easily reversible
  • Monitoring
    • partial thromboplastin time (PTT)
  • Antagonist
    • protamine sulfate 
      • positively charged to bind negatively charged heparin
Warfarin (Coumadin)
  • Mechanism
    • ↓ hepatic synthesis of vitamin K-dependent clotting factors
      • prevents the reduction of vitamin K, a necessary step in the synthesis of clotting factors
        • vitamin K epoxide reductase is inhibited
        • γ-carboxylation of clotting factors cannot occur 
      • affected clotting factors include
        • II
        • VII
        • IX
        • X
        • protein C
        • protein S
    • no effect on clotting factors already present
    • affects the extrinsic pathway
  • Clinical use
    • chronic anticoagulation
      • DVT prophylaxis
      • post-STEMI
      • heart valve damage
      • atrial arrhythmias
  • Toxicity
    • transient hypercoagulability
      • transient protein C deficiency when beginning warfarin treatment
        • due to short half life of protein C
      • can lead to skin necrosis and dermal vascular thrombosis
      • give heparin as you begin warfarin treatment
    • bleeding
    • teratogenic
      • bone dysmorphogenesis
      • not used in pregnancy
    • drug interactions
      • P450 metabolism 
        • inducers → ↓ PT
          • increase in P450 degrades more warfarin and levels fall
          • mnemonics
            • Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs
              • Chronic
              • Alcohol
              • St. John’s wort
              • Phenytoin
              • Phenobarbital
              • Nevirapine
              • Rifampin
              • Griseofulvin
              • Carbamazepine
        • inhibitors → ↑ PT
          • decrease in P450 degrades less warfarin and levels rise
          • mnemonics
            • AAA RACKS In GQ Magazine
              • Acute Alcohol Abuse
              • Ritonavir
              • Amiodarone
              • Cimetidine/Ciprofloxacin
              • Ketoconazole
              • Sulfonamides
              • Isoniazid
              • Grapefruit juice
              • Quinidine
              • Macrolides
      • ASA, sulfonamides, and phenytoin
        • displace warfarin from plasma proteins, leading to increased free fraction → ↑ PT
      • cholestyramine
        • ↓ oral absorption
          • due to low pKa
  • Pharmacology
    • oral
    • long half life (>30 hr)
    • small, lipid-soluble
  • Monitoring
    • prothrombin time (PT)
    • INR
      • (tested PT / reference PT)^(calibration value)
  • Antagonist 
    • vitamin K (slow onset)
    • fresh frozen plasma (fast onset) 
Lepirudin and Bivalirudin
  • Mechanism
    • direct inhibtors of thrombin (IIa)
  • Clinical use
    • alternative to heparin
      • e.g. during HIT
    • unstable angina during percutaneous transluminal coronary angioplasty


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Qbank (3 Questions)

TAG
(M1.HE.18) A 58-year-old Caucasian male with a history of peripheral vascular disease is admitted to the hospital with a painful, pulseless foot. He is prescribed antiplatelet and anticoagulant drugs. Which of the following matches a drug with its correct characteristic?
Topic Review Topic

1. Warfarin: directly inhibits thrombin
2. Heparin: activates antithrombin 3
3. Aspirin: reversibly inhibits COX-1
4. Clopidogrel: antagonizes ADP receptors on endothelial cells
5. Prasugrel: reduced risk of bleeding compared to other drugs in its class

PREFERRED RESPONSE ▶
TAG
(M1.HE.28) A 66-year-old male with a history of deep venous thrombosis is admitted to the hospital with shortness of breath and pleuritic chest pain. He is treated with an anticoagulant, but he develops significant hematochezia. His BP is now 105/60 and HR is 117; both were within normal limits on admission. The effects of the anticoagulant are virtually completely reversed with the administration of protamine. Which of the following was the anticoagulant most likely administered to this patient? Topic Review Topic

1. Warfarin
2. Enoxaparin
3. Heparin
4. Bivalirudin
5. Dabigatran

PREFERRED RESPONSE ▶
TAG
(M1.HE.60) A 48-year-old woman is admitted to the hospital and requires anticoagulation. She is administered a drug that binds tightly to antithrombin III. Which of the following drugs was administered? Topic Review Topic

1. Aspirin
2. Warfarin
3. Dabigatran
4. Rivaroxaban
5. Enoxaparin

PREFERRED RESPONSE ▶
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