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
Antiplatelet Drugs- Vorapaxar
Metabolized by CYP3A4 and CYP2J2
Half-life is 8 days
Antiplatelet Drugs- Aspirin: Precautions and Contraindications
Hypersensitivity
- Cross-sensitivity with NSAIDs
- Pregnancy category C (D in third trimester)
- Reye’s syndrome in children
Antiplatelet Drugs- Clopidogrel and Ticlopidine: Precautions & Contraindications
Avoid in patients with liver dysfunction
Antiplatelet Drugs- Vorapaxar: Precautions and Contraindications
Black box warning not to use in patients with history of stroke or transient ischemic attack (TIA)
Antiplatelet Drugs: ADRs
- All: Bleeding
- Aspirin: may cause GI bleeding, salicylism (tinnitus)
- Ticlopidine: neutropenia
- Dagigatran: dyspepsia and gastritis-like symptoms
Antiplatelet Drugs: Interactions
Concurrent use of other antiplatelet, anticoagulant, or fibrinolytic drugs
Aspirin- herbals (gingko, garlic, ginseng); NSAIDs
Clopidogrel- PPIs; CYP2C19 inhibitors
Ticlopidine- antacids; digoxin; cimetidine
Antiplatelet Drugs- Aspirin: Clinical Use and Dosing
MI prevention: 75-162 mg daily
Persistent atrial fibrillation: 75 to 325 mg daily
Stroke or TIAs: 50 to 100 mg daily
Antiplatelet Drugs- Clopidogrel: Clinical Use and Dosing
MI prevention: 75 mg daily
ST-elevation acute coronary syndrome: 300 mg daily if younger than 75 years of age and 75 mg daily if older than 75 years of age
Antiplatelet Drugs- Ticlopidine: Clinical Use and Dosing
Prevents stones in patients intolerant of acetylsalicyclic acid: 250 mg twice daily
Antiplatelet Drugs- Vorapaxar: Clinical Use and Dosing
Combined with aspirin or clopidogrel to prevent thrombotic cardiovascular events
Antiplatelet Drugs: Patient Education
Administration
- Take aspirin with a full glass of water
- Aspirin must be stopped 7 days before surgery
- Clopidogrel should not be taken with PPIs (OTC Prilosec or Omeprazole)
ADRs
- Aspirin toxicity
- Bleeding
Hematopoietic Growth Factors: Examples, MOA, Use
Epoetin alfa (Epogen, EPO, procrit) and darbepoetin alfa (Aranesp)
- Stimulate erythropoiesis (RBC)
- Used for treatment of anemia caused by end-stage renal disease, AIDs, or chemotherapy
- Preoperatively to prepare for allogenic transfusions
Granulocyte colony-stimulating factor (filgrastim [Neuopgen], pegfilgrastim [Neulasta])
- Stimulates granulocyte formation
- Neutropenia caused by bone cancer and chemotherapy
Hematopoietic Growth Factors: Pharmacokinetics
Well-absorbed subQ
May be given IV
Metabolism and excretion not well understood
Hematopoietic Growth Factors: Precautions and Contraindications
Epoetin alfa and darbepoetin alfa
- HTN is only contraindication
- Increased risk of tumor growth
- Pregnancy category C
Filgrastim and pegfilgrastim
- Hypersensitivity to Escherichia coli
- Pregnancy Category C
Hematopoietic Growth Factors: ADRs
- All can produce bone pain
- Epoetin alfa and darbepoetin
- – Seizures
- – HTN
- – Decreased overall survival rate and/or tumor growth in patients with certain cancers
- Filgrastim and Pegfligrastim
- – Hypersensitivity
Hematopoietic Growth Factors: Drug Interactions, Clinical Use, Dosing
Few drug interactions
Clinical Use and Dosing
- Epoetin alfa to treat anemia
- – 50-150 U/kg 3x/week, depending on diagnosis
- – For allogenic transfusion: 300 U/kg/day given 10 days prior to surgery, day of surgery, and for 4 days after surgery
- Darbepoetin
- – 0.45 to 2.25 mcg/kg once weekly
Hematopoietic Growth Factors: Monitoring
Darbepoetin alfa: Hgb weekly
Epoetin alfa: Hct twice weekly, BP
Ferritin for both
Hematopoietic Growth Factors: Patient Education
Administration - Self administration of subQ medication - Use of iron supplements ADRs - HTN, allergic reactions
Iron Preparations: Pharmacokinetics
Build serum iron and iron storage in the body
Pharmacokinetics
- enhanced absorption if iron stores low
- ferrous form absorbed more readily
- food affects absorption
- eliminated via shedding of GI mucosal cells or via bleeding
Iron Preparations: Precautions, Contraindications, ADRs, Drug Interactions
Precautions and Contraindications
- Hemochromatosis and hemolytic anemia
ADRs
- GI symptoms (constipation, GI upset)
- Acute toxicity possible, especially in children
Drug Interactions
- chelation
- decreased absorption
Iron Preparation: Clinical Use and Dosing
Iron-deficiency anemia
- Treatment for 3-4 months after hgb/hct return to normal
- Adults: 150-300 mg elemental iron daily
- Premature infants: 2-4 mg/kg/day
- infants and young children: 4-6 mg/kg/day
Iron Preparations: Monitoring
Reticulocyte count 7-10 days after starting therapy
Hgb at 2 weeks, then based on individual risk
Iron Preparation: Patient Education
Prevention
- Adequate intake of iron in diet
Administration:
- Take on empty stomach, if tolerated
- Take with vitamin C to enhance absorption
- Avoid taking with dairy products, calcium, and antacids
ADRs
- Constipation
- Acute iron toxicity with overdose; keep away from children
Folic Acid: Deficiency Causes & Pharmacokinetics
Deficiency Causes:
poor intake, impaired absorption, increased demand, impaired utilization
Pharmacokinetics:
oral, IM, or subQ well absorbed; metabolized by liver; excreted in urine and feces
Folic Acid: Clinical Use & Deficiency Prevention
Anemia caused by folic acid deficiency
- Initial dose: 1 mg/day in adults and children
- Maintenance dose
- –infants 0.1 mg/day
- –pregnant or lactating women: 0.8 mg/day
Prevention of deficiency
- 0.4 mg/day prior to conception and during pregnancy
Vitamin B12: Etiology & Pharmacokinetics
Etiology
- poor intake (vegans, vegetarians); impaired absorption caused by lack of intrinsic factor, diseases of ilium, stasis (constipation); gastrectomy, bariatric surgery
Pharmacokinetics
- IM, subQ, or intranasal well absorbed
- Stored in liver and excreted in urine
Vitamin B12: Clinical Use
Prevention of Deficiency:
- Pregnancy: 2.2 mcg/day, lactation 2.6 mcg/day
- Infants: 0.3 to 0.5 mcg/day
- Children age 1-10 years: 0.7 to 1.4 mcg/day
Treatment of Deficiency:
- 1000 mcg oral cobalamin daily for 6-12 weeks
Pernicious anemia
- Initial dose 1,000 mcg/day IM or subQ for 7 days, then 100 to 1,000 mcg IM per week for a month
Maintenance
- 1,000 mcg IM monthly
- 500 mcg intranasal cyancobalamin weekly
- 1,000 mcg oral daily
