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  1. Indications
    1. Ventricular arrhythmias
      1. Stable Wide Complex Tachycardia
      2. Stable Ventricular Tachycardia
      3. Pulseless Ventricular Tachycardia
      4. Pulseless Ventricular Fibrillation
    2. Supraventricular arrhythmias
      1. Supraventricular Tachycardia
      2. Ventricular rate control
        1. Rapid atrial arrhythmias (Atrial Fibrillation)
        2. Accessory pathway (Wolff-Parkinson-White Syndrome)
      3. Atrial Fibrillation Cardioversion
        1. Time to Cardioversion: 8-24 hours
        2. Conversion Rate: 43-68%
        3. Chronic Efficacy: 55-65%
  2. Mechanism
    1. Class IA Antiarrhythmic
      1. High affinity for inactive sodium channels
      2. Most effective in tissue with long action potentials
    2. Class II Antiarrhythmic
      1. Non-competitive Beta-Blocker
    3. Class III Antiarrhythmic
      1. Prolongs refractory period via action potential
    4. Class IV Antiarrhythmic
      1. Weak Calcium Channel Blocker
  3. Pharmacokinetics
    1. Half life: 13 to 103 days
    2. Effective plasma concentration: 1-2 ug/ml
  4. Effects
    1. General cardiac effects
      1. Inhibits abnormal automaticity
      2. Increases refractory period in all conduction system
      3. Anti-Anginal effects
    2. Atrial effects
      1. Slows sinus node rate
      2. Slows atrioventricular node conduction
    3. Ventricular effects
      1. Prolongs QT Interval
      2. Prolongs QRS Duration slightly
    4. Non-cardiac effects
      1. Peripheral vascular dilatation
  5. Adverse Effects
    1. Cardiac Adverse Effects
      1. Symptomatic Bradycardia
      2. Heart Block
      3. Hypotension (Pressure support often required)
      4. Congestive Heart Failure exacerbation
      5. Proarrhthmia effect (2-5%)
    2. Eye
      1. Optic Neuritis
      2. Corneal deposits (90%)
        1. Yellow-brown microcrystal deposits in Cornea
        2. Deposits appear within weeks of treatment
        3. May interfere with vision in 10% of cases
          1. Halos in peripheral visual fields (night-time)
          2. Visual Acuity rarely decreased
    3. Skin Deposits
      1. Photodermatitis (25%)
      2. Grayish-blue Skin Discoloration (5-9%)
    4. Neurologic adverse effects
      1. Paresthesias
      2. Tremor
      3. Ataxia
      4. Headache
    5. Endocrine adverse effects
      1. Hypothyroidism (6%)
      2. Hyperthyroidism (2%)
    6. Gastrointestinal adverse effects
      1. Constipation (20%)
      2. Hepatocellular necrosis
    7. Pulmonary adverse effects
      1. Pneumonitis
      2. Pulmonary fibrosis (up to 17%)
  6. Drug Interactions
    1. Decreased Heart Rate and AV Node Conduction
      1. Beta Blockers
      2. Calcium Channel Blockers
    2. QT Prolongation with proarrhythmia risk
      1. Fluoroquinolones
    3. Reduces clearance of other drugs
      1. Warfarin (Coumadin)
      2. Theophylline
      3. Quinidine
      4. Procainamide
      5. Flecainide
      6. Digoxin (Levels may be increased by 70%)
      7. Simvastatin (risk of Myopathy if dose >20 mg/day)
      8. Sildenafil (Viagra)
      9. Cyclosporine
  7. Dosing: Adult
    1. Life-threatening arrhythmia (Wide Complex Tachycardia)
      1. Intravenous Dosing
        1. Load: 150 mg over 10 minutes
          1. May be repeated in 10 to 30 minutes
        2. Maintenance
          1. First: 1 mg/min for 6 hours
          2. Next: 0.5 mg/min for 18 hours
          3. Last: Reduce IV dose and convert to oral dosing
      2. Oral Dosing
        1. Load: 800 to 1600 mg PO per day in divided dosing
          1. Continue daily until total of 10 grams given
        2. Maintenance: 200-400 mg PO qd
      3. Maximum: 2 grams per day total
    2. Pulseless arrhythmia (e.g. Ventricular Fibrillation)
      1. Load: 300 mg in 20-30 ml Saline rapid IV infusion
      2. Maintenance and maximum dose as above
    3. Atrial Fibrillation
      1. Load: 600 to 800 mg PO per day in divided dosing
        1. Continue daily until total of 10 grams given
      2. Maintenance: 200 mg PO qd
  8. Dosing: Child (Life-threatening arrhythmia)
    1. Dose: 5 mg/kg IV or IO
    2. Administer over 20 to 60 minutes (unless pulseless)
  9. Monitoring
    1. Baseline labs
      1. Chest XRay
      2. Thyroid Stimulating Hormone (TSH)
      3. Aspartate Aminotransferase (AST)
      4. Alanine Aminotransferase (ALT)
      5. Prothrombin Time with INR
      6. Pulmonary Function Tests (including DLCO)
      7. Consider ophthalmologic baseline exam
      8. Serum Digoxin level (as needed)
    2. Initial Monitoring
      1. Closely monitor heart rhythm in first week of therapy
      2. Prothrombin Time with INR if on Warfarin
    3. Repeat Lab testing every 6 months
      1. Chest XRay
      2. Thyroid Stimulating Hormone (TSH)
      3. Aspartate Aminotransferase (AST)
      4. Alanine Aminotransferase (ALT)
      5. Serum Digoxin level (as needed)
    4. Additional monitoring
      1. Chest XRay and Pulmonary Function Tests
        1. Indicated for suspected pneumonitis
  10. References
    1. Katzung (1989) Pharmacology, Lange, p. 176
    2. (2000) Circulation 102(suppl I):86
    3. Siddoway (2003) Am Fam Physician 68:2189

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