Pharmacology Quick Reference: Anticoagulants, Anemia, and Antiarrhythmics

Posted on Feb 14, 2025 in Pharmacy

Anticoagulants

Unfractionated Heparin (UFH)

  • Mechanism: Antithrombin III, Xa/IIa
  • Dosage:
    • Loading dose & continuous infusion: 80 units/kg load, 18 units/kg/h infusion
    • Prophylaxis: 5000 units subcutaneously
  • Contraindications: HIT (Heparin-Induced Thrombocytopenia), hypersensitivity, thrombocytopenia, active bleeding or risk of bleeding
  • Monitoring: aPTT (activated Partial Thromboplastin Time), baseline and every 6 hours until 2x therapeutic level; goal 1.5-2.5x baseline
  • Reversal Agent: Protamine sulfate

Low Molecular Weight Heparin (LMWH)

  • Mechanism: Antithrombin III, Xa
  • Examples: Enoxaparin, dalteparin, tinzaparin
  • Administration: Subcutaneously
  • Considerations: Renal dose adjustments and limits
  • Side Effects: Bleeding, injection site pain, low incidence of HIT
  • Monitoring: Generally not required (except in renal impairment, obesity, pregnancy, pediatrics, where Anti-Xa levels may be used)
  • Reversal Agent: Protamine sulfate

Pentasaccharides

  • Mechanism: Antithrombin III, Xa
  • Example: Fondaparinux
  • Administration: Once subcutaneously
  • Considerations: Renal dose adjustments; contraindicated in CrCl < 30 mL/min, caution if 30-50 mL/min, hypersensitivity, thrombocytopenia
  • Reversal Agent: None
  • Monitoring: CBC (Complete Blood Count), platelets, serum creatinine (SCr), blood in stool; Anti-Xa levels if CrCl > 30 mL/min

Direct Thrombin Inhibitors

  • Mechanism: Bind to thrombin site
  • Examples:
    • Argatroban: Use with hepatic dysfunction; monitor aPTT 2 hours after dose; approved for HIT
    • Bivalirudin: Use with renal impairment/proteolytic cleavage; caution in renal impairment

NOAC (Novel Oral Anticoagulants) – Direct Thrombin Inhibitor

  • Mechanism: Bind to thrombin site
  • Example: Dabigatran
  • Administration: After 5-10 days of parenteral anticoagulation, start < 3 hours prior to next dose of parenteral anticoagulant
  • Contraindications: CrCl < 30 mL/min
  • Reversal Agent: Idarucizumab

Vitamin K Antagonist

  • Example: Warfarin
  • Mechanism: Affects factors II, VII, IX, and protein C

Factor Xa Inhibitors

  • Examples: Rivaroxaban, apixaban, edoxaban
  • Administration: Take rivaroxaban with food
  • Considerations:
    • If co-administered with CYP3A4 inhibitors, reduce or avoid apixaban use
    • Contraindicated in renal impairment (CrCl < 30 mL/min for rivaroxaban), hepatic impairment or CYP interactions (apixaban), hepatic impairment (edoxaban)
    • Take edoxaban after 5-10 days of initial parenteral anticoagulation
  • Reversal Agent: Andexanet alfa (for apixaban and rivaroxaban)

Thrombolytics

  • Examples: Alteplase, tenecteplase, reteplase
  • Contraindications: Active bleeding, history of CVA (Cerebrovascular Accident), uncontrolled hypertension, recent intracranial/spine surgery/trauma, not for submassive PE (Pulmonary Embolism) with minor RV (Right Ventricular) dysfunction, minor myocardial necrosis, no clinical worsening, or low-risk PE

Venous Thromboembolism (VTE)

Post-Hemorrhage Management

  • Cause: Blood loss, RBC and hemoglobin decrease from hemodilution
  • Volume Loss:
    • 10-15% total volume loss = vascular instability
    • >30% total volume loss = hypotension & tachycardia
    • >40% loss = hypovolemia, altered mental status (AMS), hypotension, tachycardia
  • Treatment: Restore volume, transfuse, treat shock

Anemia

Sickle Cell Anemia

  • Genetics: Autosomal recessive = abnormal hemoglobin in RBCs
  • Risks: Chronic hemolytic anemia, stroke, heart/renal failure, infection, blocked microvasculature
  • Treatment:
    • Hydroxyurea: Reduces crisis, increases RBC hemoglobin F level & H2O content, alters adhesion of RBC to endothelium
      • Dose: 15mg/kg/day x 12 weeks until marrow suppression, max 35mg/kg/day
      • Side Effects: Myelosuppression, hyperpigmentation, alopecia, cancer risk, photophobia
    • Pain Management: ASA (Aspirin), NSAIDs (caution renal/peptic ulcer), opioids (watch sedation & respiratory depression, N/V/itching)

Iron Deficiency Anemia

  • Characteristics: Microcytic
  • Causes: Dietary deficiency, decreased absorption, increased requirements (menstruation, lactation), blood loss
  • Normal Iron: 3-4g
  • Diagnosis: Glossal pain, smooth tongue, pica, pagophagia
  • Labs: Low serum Fe, ferritin, transferrin saturation, MCV
  • Treatment:
    • Diet: Red meat, fish, poultry
    • Pharmacological: Iron supplements (elemental iron), IV for severe deficiency or PO intolerance
      • Ferrous fumarate 33% elemental
      • Ferrous gluconate 11.6%
      • Ferrous sulfate 20%
      • Ferrous sulfate anhydrous 30%
      • Dose: 2-3mg/kg 2-3 divided doses daily
      • Side Effects: Discolored stool, constipation/diarrhea, nausea/vomiting, GI upset
      • Other Forms: Slow release, sustained release
      • IV Iron:
        • Dextran 200-500mg 1x, 0.5mL test dose before therapy
        • Gluconate 125mg daily x 8 days
        • Sucrose 200mg daily x 5 in 14-day period
        • Carboxymaltose >50 kg patient: 750mg on day 1; repeat after at least 7 days
        • Ferumoxytol 510mg on day 1, repeat within 3-8 days
Response Time: Hemoglobin increase within 1 week, treat at least 3-6 months, 1-year treatment, increase ferritin to 50ng/mL, increase iron to 50ng/mL Decreased PO Iron Absorption: Antacids (Al, Ca, Mg products), PPIs, H2 agonists; tetracycline, fluoroquinolones (separate administration at least 2 hours)

Anemia of Chronic Kidney Disease (CKD)

  • Definition: Kidney damage or GFR < 60 mL/min/1.73 m2 for > 3 months
  • Mechanism: Reduced erythropoietin (EPO) production
  • Treatment:
    • Treat underlying cause
    • Erythropoiesis-Stimulating Agents (ESA): Check iron status for adequate stores, start therapy when hemoglobin < 10g/dL, hold if > 12g/dL
      • Epoetin alfa 50-100 units/kg subcutaneously/IV x3/week
      • Darbepoetin alfa 0.45mcg/kg x1 per week or 0.75mcg/kg once every 2 weeks
      • Side Effects: Hypertension, Nausea/Headache/fever, bone pain, fatigue

Vitamin B12 Deficiency

  • Characteristics: ↓ Vitamin B12, ↑ MCV > 100, ↑ methylmalonic acid, ↑ homocysteine, Schilling Test
  • Treatment:
    • Diet: 2.4mcg daily
    • Pharmacological: 1000-2000mcg PO daily x 1-2 weeks, maintain 1000mcg daily
    • Malabsorption Deficiencies: 100mcg IM/SubQ daily x 7 days, taper as directed, maintain 100mcg IM/SubQ monthly

Folate Deficiency

  • Minimum Daily Requirement: 50-100mcg
  • Non-Pregnant: 400mcg
  • Pregnant: 600mcg
  • Lactating: 500mcg
  • Pharmacological: 1mg PO daily, highest OTC 800mcg

Aplastic Anemia

  • Definition: Bone marrow doesn’t make blood cells = pancytopenia with hypocellular marrow
  • Treatment: Infusion, antibiotics, stem cell transplant & immunosuppression

Anemia Definition

  • Male < 13g/dL
  • Female < 12g/dL

Antiarrhythmics

Class I: Na+ Channel Blockers (DO NOT USE IN HEART FAILURE)

Ia. Block Na+ and K+ channels

  • Quinidine: Side effects include hearing/vision changes, hypotension, reflex tachycardia, torsades; use for atrial & ventricular arrhythmias
  • Procainamide: Side effects include lupus-like symptoms, hypotension, torsades; use for ventricular arrhythmias, metabolized in liver to NAPA (prolongs AP, acts as Class III)
  • Disopyramide: Side effects include anticholinergic effects, torsades; use for atrial arrhythmias

Ib. Shorten AP (QRS interval) – Not for atrial arrhythmias

  • Lidocaine (parenteral): Side effects include hypotension, drowsiness, seizures; decreases depolarization of ventricles, no effect on PR interval, QT prolongation
  • Mexiletine (PO): Side effects include high CNS, GI, hematologic effects; rarely used

Ic. Reduce phase 0 upstroke velocity

  • Flecainide: Side effects include dizziness, blurred vision, torsades
  • Propafenone: Side effects include dizziness, blurred vision, bronchospasm, torsades
  • Uses: Supraventricular arrhythmia
  • Contraindications: Structural heart disease

Class II: Beta-Blockers

  • Depress SA node, slow AV node conduction velocity, decrease contractility
  • Side Effects: Bronchospasm, depression, fatigue, impotence, bradycardia, hypotension, heart block
  • Use: Atrial and ventricular arrhythmias

Class III: K+ Channel Blockers

  • Prolong AP by lengthening repolarization
  • Amiodarone (PO and parenteral, antiarrhythmic of choice): Side effects include photosensitivity, corneal microdeposits, hypo/hyperthyroidism, hepatotoxicity, pneumonitis, N/V, constipation; use for ventricular arrhythmias, AFib; preferred agent in structural heart disease, CYP450 substrate & inhibitor (decrease warfarin & digoxin 50%), long half-life 26-107 days, give loading dose
  • Sotalol (PO): Side effects include bronchospasm, depression, fatigue, impotence, bradycardia, hypotension, heart block, torsades, especially with renal dysfunction, reduced EF, structural heart disease; use: non-selective (low doses), non-selective & K+ blocker (high doses), not to convert AFib, contraindication: heart failure
  • Dofetilide (PO, certified Rx): Side effects include headache, dizziness, chest pain, torsades; potent/pure K+ channel blocker, use for AFib/Flutter, ventricular arrhythmia, heart failure; drug interactions: azoles, macrolides, protease inhibitors, drugs that prolong QT; renal dose, contraindicated CrCl < 20, hemodynamic/EKG monitoring for 72 hours
  • Dronedarone (PO): Similar to amiodarone, not as effective, no thyroid side effects, less ocular/derm toxicity; only use for non-permanent AFib, CYP3A4 inhibitor, interacts with drugs that prolong QT; BBW: permanent AFib, heart failure, cause liver failure
  • Ibutilide (parenteral): Side effects include torsades, increased in patients with low EF or abnormal electrolytes, not for maintenance, emergency only, cardiovert AFib/Flutter

Class IV: Ca Channel Blockers

  • Negative chronotropes, dromotropes, inotropes
  • Diltiazem & Verapamil: Side effects include constipation (verapamil), bradycardia, hypotension (common), heart block, peripheral edema; contraindication: heart failure, doesn’t cardiovert

Miscellaneous Antiarrhythmics

  • Adenosine: Blocks conduction through AV node, interrupts reentry through AV node, causes asystole; side effects include chest pain, flushing, SOB; cardioversion of SVT, short half-life & duration of action
  • Digoxin: Increases vagal tone, decreases SA node, reduces impulse through AV node, side effects include GI upset, visual disturbances, heart block, headache; use for AFib, heart failure (rate control), renal dose
  • Magnesium: Decreases membrane excitability; use for torsades – 2nd line after cardioversion

Anticoagulants (as Antiarrhythmics)

  • Warfarin: Prevents Vitamin K synthesis; side effects include bleeding; use for AFib/Flutter, onset of action delayed 5-7 days, bridge, MUST monitor INR
  • NOACs: Side effects include bleeding
    • Dabigatran: Direct thrombin inhibitor; use for AFib, DVT/PE treatment, renal dose, interacts with P-glycoprotein, has antidote
    • Rivaroxaban & Apixaban: Direct Xa inhibitors, use for AFib, DVT/PE (treatment and prophylaxis), renal dose, drug interactions with P-Glycoprotein, CYP3A4