Drugs for Blood Clotting Disorders

• What is thrombosis?

  Pathogenic state of inappropriate haemostasis
• Name one condition associated with thrombosis.

  Atrial fibrillation
• What is a thrombus?

  A blood clot formed in vivo
• What is the structure of a thrombus?

  White head and red tail
• What are the two main types of thrombus?

  1. Arterial thrombus
  2. Venous thrombus
• What characterizes an arterial thrombus?

  Large head formed from platelets
• What primarily triggers arterial thrombosis?

  Rupture of an atherosclerotic plaque
• How is arterial thrombus mainly treated?

  With antiplatelet drugs
• What is a venous thrombus composed of?

  A fibrin web with red blood cells
• What is the primary cause of venous thrombus formation?

  Activation of the clotting system
• How are venous thromboembolic disorders primarily treated?

  With anticoagulant drugs
• What are the three classes of drugs developed for blood clotting disorders?

  Anticoagulants, antiplatelet agents, thrombolytics

  
• What do anticoagulants do?

  Modify blood clotting mechanisms
• What is the role of antiplatelet agents?

  Inhibit platelet aggregation
• What do thrombolytic agents do?

  Break down fibrin

  
• What is the action of heparin?

  Activates antithrombin III

  
• How does heparin affect antithrombin III?

  Increases its activity by ~1000x
• What is the pharmacodynamics of low molecular weight heparins (LMWH)?

  Inactivate factor Xa via antithrombin III

  
• What is the route of administration for heparin?

  IV or subcutaneously
• What is the half-life of heparin?

  Shorter than LMWH
• What are the side effects of heparin?

  Bleeding and hypersensitivity
• How is heparin overdose treated?

  With IV protamine
• What is warfarin's mechanism of action?

  Inhibits vitamin K-dependent clotting factors

  
• What is the lag period for warfarin's effect?

  1-2 days
• What are the side effects of warfarin?

  Bleeding and skin necrosis
• How is warfarin overdose treated?

  With vitamin K or FFP

  
• What is the clinical use of warfarin?

  Prevent venous thrombosis and pulmonary embolus
• What is the purpose of warfarin in patients with atrial fibrillation?

  Prevent arterial thromboemboli
• What is the primary side effect of warfarin?

  Bleeding and skin necrosis
• What type of molecule is warfarin?

  Small, lipid-soluble molecule
• How is warfarin absorbed in the body?

  Rapidly and almost totally from the GIT
• When do warfarin levels peak in the blood after administration?

  0.5-4 hours
• What is the volume of distribution for warfarin?

  Low volume of distribution
• What percentage of warfarin is plasma protein bound?

  ~99%
• How is warfarin metabolized in the body?

  By CYP450 enzymes in the liver
• What is the half-life of warfarin?

  15-80 hours
• What is the typical dose range for warfarin?

  2-112 mg/week
• What are the clinical uses of warfarin?

  • Prevent progression of venous thrombosis
  • Prevent pulmonary embolus
  • Prevent arterial thromboemboli in atrial fibrillation
  • Recommended anticoagulation duration for calf vein thrombosis: 6 weeks
  • Recommended duration for DVT or PE: 3 months
• What is the initial anticoagulation treatment usually started with?

  Heparin and an oral anticoagulant
• How is the effect of heparin monitored?

  By activated partial thromboplastin time (APTT)