NR 566 - Final Exam Review Week 5 Review Chapter 18: Drugs Affecting the Hematopoietic System

1. Anticoagulants (Oral & Parenteral)

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Oral Anticoagulants

Warfarin (Coumadin):

• Inhibits synthesis of vitamin K-dependent clotting factors X, IX, VII, and II (prothrombin).

Pharmacokinetics:

• Well-absorbed when taken orally.
• Metabolized by CYP 1A2 and 2C9.
• Half-life of 3 to 4 days.

Precautions and contraindications:

• Pregnancy category X.
• Use cautiously in patients with fall risk, dementia, or uncontrolled hypertension.
• Avoid in hypermetabolic state.
• The major adverse drug reaction is bleeding (Antidote is vitamin K).
• Many drug interactions, including (but not limited to):
  • Antiplatelet drugs.
  • Thrombolytic drugs.
  • Oral contraceptives, carbamazepine, Vitamin K-containing foods, etc.

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/d if weight greater than 80 kg).
• Consider lower dose in the following situations:
  • Older than 75 years.
  • Multiple comorbid conditions.
  • Elevated liver enzymes.
  • Changing thyroid status.
• Dose to maintain international normalized ratio (INR) between 2 and 3.

Monitoring:

• INR daily until in therapeutic range for 2 consecutive days.
• Then two or three times weekly for 1 to 2 weeks.
• Then less frequently but at least every 6 weeks.

Rivaroxaban (Xarelto): Factor Xa inhibitor. Apixaban (Eliquis): Factor Xa inhibitor.

• Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation.
• Prophylaxis of DVT following knee replacement surgery.
• Treatment of DVT and PE.

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Parenteral Anticoagulants

Heparin:

• Binds with the antithrombin III.
• Inactivates factors IXa, Xa, XIIa, XIII.

Pharmacokinetics:

• Given IV or subcutaneously (SC).
• Extensively protein-bound.
• Metabolized by liver and renally eliminated.

Precautions and contraindications:

• Pregnancy category C.
• Avoid in advanced hepatic or renal disease.
• Avoid in bleeding disorders or active bleeding.

Adverse drug reactions (ADRs):

• May cause thrombocytopenia.
• Life-threatening bleeding.
• Pain at injection site (SC).
• Antidote is protamine sulfate.

Drug interactions:

• Cephalosporins and penicillins; Warfarin, antiplatelets and thrombolytics; Valproic acid.

Clinical use and dosing:

• Given 2 hours pre-operatively.
• Maintenance every 8 to 12 hours for 7 days after surgery.
• Heparin is processed into smaller molecules → low molecular-weight heparins (LMWH).
• Inactivates factor Xa.

Enoxaparin:

• DVT or PE.
• Given 2 hours before surgery.

Fondaparinux: Selective inhibitor of antithrombin III and factor Xa inhibitor.

• DVT.
• Hip fracture surgery or knee replacement.

Dalteparin:

• Prevention of DVT after abdominal surgery or hip replacement.

Monitoring for Anticoagulants:

• Activated partial thromboplastin time.
• Platelet and hematocrit (Hct) every 2 to 3 days initially.

Patient Education for Anticoagulants:

• Administration.
• Warfarin dosing may vary day to day.