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Hematopoietic Flashcards

1
Q

Oral Anticoagulants- Warfarin: Pharmacodynamics

A

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

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2
Q

Oral Anticoagulants: Factor Xa Inhibitors

A

Rivaroxabon (Xarelto)
Apixaban (Eliquis)
Endoxaban (Savaysa)
Betrixaban (Bevyxxa)

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3
Q

Parenteral Anticoagulants- Heparin, Low-Molecular-Weight Heparin, Fondaparinux (Arixta): Pharmacodynamics

A

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

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4
Q

Warfarin: Pharmacokinetics, Precautions, & Contraindications

A

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
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5
Q

Warfarin: ADRs & Drug Interactions

A

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
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6
Q

Warfarin: Clinical Use and Dosing

A

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

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7
Q

Warfarin: Monitoring

A
  • 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
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8
Q

Factor Xa Oral Anticoagulants: Use

A

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
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9
Q

Factor Xa Oral Anticoagulants: Drug Interactions

A
  • Betrixaban and P-gylcoprotein (P-gp) inhibitors
  • Apixaban and P-gp or CYP3A4 inhibitors
  • Rivaroxaban and P-gp/CYP3A4 inducers
  • Vorapaxar and CYP3A inhibitors
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10
Q

Factor Xa Inhibitors: ARDs and Clinical Dosing

A

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
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11
Q

Heparin: Pharmacokinetics, Precautions, and Contraindications

A

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
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12
Q

Heparin: ADRs & Drug Interactions

A

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
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13
Q

Heparin: Clinical Use and Dosing

A

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
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14
Q

Heparin: Monitoring & Patient Education

A

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
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15
Q

Antiplatelet Drugs: Examples & MOA

A

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
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16
Q

Antiplatelet Drugs- Aspirin: Pharmaockinetics

A

Well-absorbed when taken orally

Metabolized in liver

Renally excreted (pH affects excretion)

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17
Q

Antiplatelet Drugs- Ticlopidine: Pharmacokinetics

A

Rapidly absorbed after oral administration

Metabolized in liver

Half-life lengthens with repeated dosing

Decreased renal clearance with age

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18
Q

Antiplatelet Drugs- Clopidogrel: Pharmacokinetics

A

Prodrug: metabolized into active metabolite

Excreted in urine and feces

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19
Q

Antiplatelet Drugs- Vorapaxar

A

Metabolized by CYP3A4 and CYP2J2

Half-life is 8 days

20
Q

Antiplatelet Drugs- Aspirin: Precautions and Contraindications

A

Hypersensitivity

  • Cross-sensitivity with NSAIDs
  • Pregnancy category C (D in third trimester)
  • Reye’s syndrome in children
21
Q

Antiplatelet Drugs- Clopidogrel and Ticlopidine: Precautions & Contraindications

A

Avoid in patients with liver dysfunction

22
Q

Antiplatelet Drugs- Vorapaxar: Precautions and Contraindications

A

Black box warning not to use in patients with history of stroke or transient ischemic attack (TIA)

23
Q

Antiplatelet Drugs: ADRs

A
  • All: Bleeding
  • Aspirin: may cause GI bleeding, salicylism (tinnitus)
  • Ticlopidine: neutropenia
  • Dagigatran: dyspepsia and gastritis-like symptoms
24
Q

Antiplatelet Drugs: Interactions

A

Concurrent use of other antiplatelet, anticoagulant, or fibrinolytic drugs

Aspirin- herbals (gingko, garlic, ginseng); NSAIDs

Clopidogrel- PPIs; CYP2C19 inhibitors

Ticlopidine- antacids; digoxin; cimetidine

25
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
26
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
27
Antiplatelet Drugs- Ticlopidine: Clinical Use and Dosing
Prevents stones in patients intolerant of acetylsalicyclic acid: 250 mg twice daily
28
Antiplatelet Drugs- Vorapaxar: Clinical Use and Dosing
Combined with aspirin or clopidogrel to prevent thrombotic cardiovascular events
29
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
30
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
31
Hematopoietic Growth Factors: Pharmacokinetics
Well-absorbed subQ May be given IV Metabolism and excretion not well understood
32
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
33
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
34
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
35
Hematopoietic Growth Factors: Monitoring
Darbepoetin alfa: Hgb weekly Epoetin alfa: Hct twice weekly, BP Ferritin for both
36
Hematopoietic Growth Factors: Patient Education
``` Administration - Self administration of subQ medication - Use of iron supplements ADRs - HTN, allergic reactions ```
37
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
38
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
39
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
40
Iron Preparations: Monitoring
Reticulocyte count 7-10 days after starting therapy Hgb at 2 weeks, then based on individual risk
41
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
42
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
43
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
44
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
45
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

Pharmacology (25 decks)

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