Anti-Coagulants Flashcards
Unfractionated Heparin (High molecular weight)
MOA: Decreases activity of clotting factors thrombin and X
Increases activity of antithrombin III
INDICATIONS: Short term immediate anticoagulation (Pulmonary embolism, acute venous thrombosis, surgical prophylaxis)
SIDE EFFECTS: Heparin induced thrombocytopenia, increased risk of bleeding, osteoporosis
MONITORING: aPTT, antifactor Xa plasma levels, activated clotting time when at high doses
Low Molecular Weight Heparin
Endoxaparin
Dalteparin
MOA: Similar mechanism but does not directly interact with thrombin
INDICATIONS: SubQ only, all three can be used for acute DVT prophylaxis during surgery, can be used for unstable angina with aspirin, renal hemodialysis
BOXED WARNING***: Epidural/spinal hematomas can occur while undergoing neuraxial anesthesia or spinal puncture. Can result in paralysis.
Risk of bleeding is lower using these, lower risk for osteoporosis (use in elderly), fewer side effects
Tinzaparin
Low molecular weight heparin
INDICATION: Treatment of acute DVT when given with warfarin
Synthetic Pentasaccharide
Fondaparinux (ARIXTRA)
MOA: Synthetic molecule similar to LMWH that inhibits factor X
INDICATIONS: No HIT risk, used for acute prophylaxis of blood clots, given daily and has the longest half life (17-21 hours), SubQ bioavailabiilty is 100%
SIDE EFFECTS: Major bleeding and thrombocytopenia in 2-3%
BLACK BOX WARNING**: Similar to LMWH (spinal hematomas), should not be used if CrCl < 30ml/min
Direct thrombin inhibitors
Argatroban
Bivalirudin (ANGIOMAX)
Lepirudin
Desrudin
Argatroban
Dabigatran
MOA: Inhibit thrombin in circulation and already attached to a clot
INDICATIONS: Usually a second line medication for pulmonary embolism, DVT, atrial fibrillation to prevent strokes, replacement of heparin especially in patients that have history of HIT
Used in combination with aspirin and clopidogrel to prevent clot formation in patients undergoing coronary artery surgery
SIDE EFFECTS: Increase bleeding, dyspepsia and gastritis, hypersensitivity to lepidurin and bivalirudin, do not discontinue abrudtly
REVERSAL: Idarucizumab
Argatroban
MOA: Direct thrombin inhibitor, univalent DTI
Continuous IV infusion with a half life of 45min
MONITORING: aPTT 1.5-3X
IINDICATION: Treatment for HTI
CONTRAINDICATION: Metabolized by hepatic CYPs and is excreted in bile, so caution in liver insuffeciency
Prolongs INR
Bivalirudin (ANGIOMAX)
MOA: Direct thrombin inhibitor, Bivalent and is reversible
Half-life of 25 min and degraded by the kidney by pepsidases
INDICATION: IV infusion used as alternative to heparin in patients undergoing a PCI (angioplasty with stent)
Warfarin
- *MOA**: Inhibits vitamin K epoxide reductase comlex 1 depleting vitamin K that interferes with vitamin-K dependent factors II, VII, IX and X
- Anticoagulant effect observed after clotting factors are eliminated (48-72 hours)
- *INDICATIONS**: Prophylaxis of DVT and pulmonary embolism, stroke for patient with afib
- Must be monitored every 1-4 weeks by INR (Want it between 2-3) - 60% success is good!
CLEARANCE: A lot of variability of warfarin clearance genotypes (CYP2C9), lower clearance means smaller dose required
SIDE EFFECTS: Almost every drug out there interacts with it, bleeding, skin necrosis, protein C depletion, Warfarin purple toe syndrome
Warfarin reversal?
Vitamin K
- *MOA:** Can limit the amount of bleeding caused by Warfarin, competitively acts, oral formulations work better but take longer
- Can use IV vitamin K, FFP, PCC, or recombinant factor VIIa
Dabigatran (oral)
MOA: Direct thrombin (IIa) inhibitor, only per mouth in class of direct thrombin inhibitors
INDICATION: Prophylaxis of DVT and pulmonary embolism, especially in patients with history of HIT, prevention of stroke with afib
REVERSAL: Idarucizumab can inhibit in case of uncontrolled bleeding
CLEARANCE: 80% renally cleared and requires acidic environment for absorption
What are the only oral anticoagulants?
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
Factor Xa inhibitors (oral)?
Rivaroxaban
Apixaban
Edoxaban
BOXED WARNING***: Discontinuing increases risk of thrombotic events. Increased rate of stroke have been observed in clinical trials. Consider coverage with another anticoagulant if need to discontinue
Rivaroxaban
MOA: Factor Xa inhibitor that has a 39% better bioavailability with food, so eat when you take it!
Eliminated by the liver (CYP3A4)
What are the parenteral anticoagulants?
Unfractionated Heparin
Low Molecular Weight Heparins
Synthetic Pentasaccharides
Direct Thrombin Inhibitors
INDICATIONS: Prophylaxis of DVT and pulmonary embolism, initial management of ACS
