Hematopoietic Flashcards
Oral Anticoagulants- Warfarin: Pharmacodynamics
Inhibits synthesis of vitamin K-dependent clotting factors X, IX, VII, II (prothrombin)
Oral Anticoagulants: Factor Xa Inhibitors
Rivaroxabon (Xarelto)
Apixaban (Eliquis)
Endoxaban (Savaysa)
Betrixaban (Bevyxxa)
Parenteral Anticoagulants- Heparin, Low-Molecular-Weight Heparin, Fondaparinux (Arixta): Pharmacodynamics
Heparin-
- Binds with antithrombin III
- Inactivates factors IXa, Xa, XIIa, XIII
LMWH
- Regular heparin is processed into smaller molecules
- Enoxaparin (Lovenox), dalteparin (Fragmin)
- Inactivates factor Xa
Fondaparinux (Arixta)
- Selective inhibitor of antithrombin III and factor Xa inhibitor
Warfarin: Pharmacokinetics, Precautions, & Contraindications
Pharmacokinetics
- well absorbed when taken orally; metabolized by CYP1A2 and 2C9; half-life of 3-4 days
Precautions and Contraindications
- Pregnancy Category X
- Use cautiously in patients with fall risk, dementia, or uncontrolled HTN
- Avoid in hypermetabolic state
Warfarin: ADRs & Drug Interactions
ADRs
- Bleeding: antidote is vitamin K
- Allergic reactions
Drug Interactions
- Many drug-drug interactions
- Antiplatelet drugs
- Thrombolytic drugs
Anticoagulant effect may be decreased by:
- Oral contraceptives, carbamazepine, etc.
- Vitamin K-containing foods
Warfarin: Clinical Use and Dosing
Drug of choice for deep vein thrombosis (DVT) and pulmonary embolism (PE)
Start at 5 mg per day (7.5 mg/day if weight is greater than 80 kg)
Consider lower dose if:
- Older than 75 years; multiple comorbid conditions; elevated liver enzymes; changing thyroid status
Dose to maintain international normalized ratio (INR) between 2 & 3
Warfarin: Monitoring
- INR daily until in therapeutic range for 2 consecutive days
- Then two or three times weekly for 1-2 weeks
- Then less frequently but at least every 6 weeks
Factor Xa Oral Anticoagulants: Use
Rivarobaxan, endoxaban, betrixaban, apixaban
- Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation
- Prophylaxis of DVT following knee replacement surgery
- Treatment of DVT and PE
Factor Xa Oral Anticoagulants: Drug Interactions
- Betrixaban and P-gylcoprotein (P-gp) inhibitors
- Apixaban and P-gp or CYP3A4 inhibitors
- Rivaroxaban and P-gp/CYP3A4 inducers
- Vorapaxar and CYP3A inhibitors
Factor Xa Inhibitors: ARDs and Clinical Dosing
ADRs
- Vorapaxar
- – GI bleed
- – Anemia
Clinical Use and Dosing
- American College of Clinical Pharmacy (ACCP) guidelines for DVT or PE after initial stabilization
- – 3 months of dibigatron, rivaroxaban, apixaban, or endoxaban for 3 months
- – Warfarin is second line
Heparin: Pharmacokinetics, Precautions, and Contraindications
Pharmacokinetics:
- Given IV or SubQ
- Extensively protein bound
- Metabolized by liver and eliminated by kidneys
Precautions and Contraindications
- Pregnancy category C
- Avoid in advanced hepatic or renal disease
- Avoid in bleeding disorders or active bleeding
Heparin: ADRs & Drug Interactions
ADRs
- May cause thrombocytopenia
- Life-threatening bleeding
- Pain at injection site (SubQ)
- Antidote is protamine sulfate
Drug Interactions
- Cephalosporins and penicillins
- Warfarin, antiplatelets, and thrombolytics
- Valproic acid
Heparin: Clinical Use and Dosing
Heparin
- Given 2 hours pre-operatively
- Maintenance every 8-12 hours for 7 days after surgery
LMWH
- Enoxaparin
- – DVT or PE
- – Given 2 hours before surgery
- Fondaparinux
- – DVT
- – Hip fx surgery or knee placement
- Dalteparin
- – Prevention of DVT after abdominal surgery or hip replacement
Heparin: Monitoring & Patient Education
Monitoring:
- Activated partial thromboplastin time (aPTT)
- Platelet and hematocrit (HCT) every 2-3 days initially
Patient Education
- Administration
- – Warfarin dosing may vary day to day
- – SubQ administration instruction for LMWH at home
- ADRs
- – Risk for bleeding
- – Vitamin K-containing foods
Antiplatelet Drugs: Examples & MOA
Aspirin
- Inhibits cyclooxygenase
- Interferes with platelet aggregation
Ticlopidine and Clopidogrel
- Reduces platelet aggregation by inhibiting adenosine diphosphate pathway
Vorapaxar
- Protease-activated receptor-1 antagonist
- Inhibits thrombin-induced and thrombin receptor agonist peptide-induced platelet aggregation
- Taken with aspirin or clopidogrel thrombin receptor agonist peptide induced platelet aggregation
Antiplatelet Drugs- Aspirin: Pharmaockinetics
Well-absorbed when taken orally
Metabolized in liver
Renally excreted (pH affects excretion)
Antiplatelet Drugs- Ticlopidine: Pharmacokinetics
Rapidly absorbed after oral administration
Metabolized in liver
Half-life lengthens with repeated dosing
Decreased renal clearance with age
Antiplatelet Drugs- Clopidogrel: Pharmacokinetics
Prodrug: metabolized into active metabolite
Excreted in urine and feces