Anticoagulation 2 Flashcards
Warfarin
Anticoagulation VitK Antagonists (VKAs) MOA 1) Inhibition of vitamin-k dependent coagulation proteins (II, VII, IX, X) 2) Inhibition of endogenous anticoagulants: (Protein C and S) • No direct effect on previously circulating clotting factors or previously formed thrombus (ie, Doesn’t dissolve clots) LAB MONITORING • Time to achieve pharmacologic effect: Dependent on elimination half-lives of coagulation proteins ─ VII = 6 hours (To depletion) ─ IX = 24 hours ─ X = 36 hours ─ II = 48-72 hours ─ Protein C = 9 hours ─ Protein S = 60 hours • ACRONYM = SNOT ADE • Hemorrhage ─ Risk greater if INR > 4 for long periods, or INRs are variable • *“purple toe syndrome” (Rare) • *warfarin-induced skin necrosis (Rare) • Alopecia WARFARIN REVERSAL • Serious bleeding; ANY INR. ─ Rapid reversal of INR = mandatory: IV Vit K • Administration of Vitamin K:
Enoxaparin
Anticoagulation
• Low Molecular Weight Heparin (LMWH) (injectable)
INDICATIONS
• ACS
─ Unstable angina
─ Non-ST-segment elevation myocardial infarction (NSTEMI)
─ ST-segment elevation myocardial infarction (STEMI)
• DVT prophylaxis
• DVT/PE treatment
- *pregnancy
MOA
• Enh Antithrombin-III (which lyses Thrombin and Factor Xa) → Thus, inhibits rate of Clotting Proteases
• Elimination = renal.
LAB MONITORING
• Platelets
• CrCL
• Anti-Xa activity in: Renal Failure, Hx Bleeding, Morbid Obese, Low Body Weight, Pregnancy
─ WARNING: Not every PT requires therapeutic monitoring!
ADE
• Hematologic
─ Major Hemorrhage, but less Risk than Unfrac Hep.
─ Thrombocytopenia
• Local: Injection site reactions
BLACK BOX WARNING
• Risk of spinal or epidural hematoma and paralysis in recent or anticipated epidural or spinal anesthesia
• Hemodialysis (Relative C/I)
─ UFH safer to use in these PTs
LMWH REVERSAL
• Protamine sulfate
─ Only 60-75% neutralization with LMWH
─ not recommended if last LMWH injection was given > 12 hours prior
─ A/E:
a) Rapid infusion = Hypotension;
b) Hypersensitivity Reaction if: Received Insulin containing Protamine, or Prev Protamine Therapy
─ C/I: Hypersens reaction to fish
Rivaroxaban, Apixaban, Edoxaban
Anticoagulation
Factor Xa Inhibitors
“-xabans”
INDICATIONS
• Prevention of stroke or systemic embolization in PTs with nonvalvular atrial fibrillation
• DVT prophylaxis
• DVT/PE treatment
MOA
• Selective inhibition of active site of factor Xa, Free & Bound
─ not require Antithrombin III for activity (Thus, “Direct”)
─ Inactivation of factor X → factor Xa via the intrinsic and extrinsic pathways
• Orally bioavailable (vs Unfrac Heparan)
LAB MONITORING
• CrCL
• LFTs
• Anti-Xa activity
ADE
• Hemorrhage
BLACK BOX WARNING
• Risk of spinal or epidural hematoma and paralysis in PTs with recent or anticipated epidural or spinal anesthesia
• Premature discontinuation of any anticoagulant ↑Risk of thrombotic events
• *CrCL >95ml/min reduces efficacy of edoxaban
DRUG INTERACTIONS
• Strong inhibitors of CYP3A4 (↑s effectiveness):
─ Azole antifungals
─ HIV protease inhibitors
• Strong inhibitors of P-glycoprotein
─ Amiodarone
─ Verapamil
• Strong inducers of CYP3A4 (↓s effectiveness)
─ Rifampin
─ Carbamazepine
Argatroban, Bivalirudin, Dabigatran
Anticoagulation
Direct Thrombin Inhibitors
Indications
• Prevention of stroke and systemic embolism in PTs with non-valvular atrial fibrillation
• Tx of VTE in PTs who have been treated with a parenteral anticoagulant for 5-10 days
• Reduction in risk of recurrent VTE in PTs who have been previously treated
MOA
1) Inhibits thrombin, both free & clot-bound
2) Inhibits thrombin-induced platelet aggregation
ADE
• Cardiovascular effects
─ ACS
─ AMI
• *Gastrointestinal Effects
─ *Esophagitis
─ dyspepsia
─ *GERD
• Hemorrhage
─ *GI BLEED
DRUG INTERACTIONS
• Strong inhibitors of P-glycoprotein (Prevents pumping drug into Intestine = High Conc in Blood)
─ *Amiodarone
─ *Verapamil
─ ketoconazole
─ clopidogrel
REVERSAL
• *idarucizumab
─ Human mAb fragment (Fab)
─ Binds to dabigatran with greater affinity than that which dabigatran binds to thrombin (“Decoy Drug”)
─ Neutralizes dabigatran anticoagulant effects
