II. Indications

  1. Hypertensive Emergency
    1. Nicardipine is now preferred instead for Hypertensive Emergency
    2. Reduces Blood Pressure rapidly
    3. However difficult to titrate due to a wide variation in bloold pressure variation
    4. Well tolerated
    5. Easily reversed by discontinuing infusion
  2. Congestive Heart Failure with pulmonary congestion
    1. Refractory to Diuretics
    2. Often used in combination with Dopamine
      1. Similar net effect to Dobutamine
    3. Nitroglycerin is preferred in Coronary Artery Disease

III. Mechanism

  1. Converted to Nitrous Oxide which stimulates cGMP
    1. cGMP stimulates dephosphorylation of myosin, resulting in arteriole Smooth Muscle relaxation
  2. Potent peripheral vasodilation
    1. Effects arterial and venous Smooth Muscle
  3. Reduces arterial Blood Pressure
    1. Reduces peripheral arterial resistance
    2. Increases venous capacitance
  4. Decreases Preload
    1. Risk of reflex Tachycardia

IV. Metabolism

  1. Red Blood Cells metabolize to Hydrocyanic acid and Liver converts to thiocyanate
    1. Onset within 2 minutes
    2. Thiocyanate effect wanes rapidly on stopping infusion
  2. Metabolites include Cyanide and Thiocyanate, risk accumulation
    1. Hepatic dysfunction
    2. High doses (esp. >3 to 10 mcg/kg/min)
    3. Prolonged infusions (>3 to 7 days)
  3. Renal Excretion

V. Pharmacokinetics

  1. Very short Half-Life
    1. Effects are seen almost immediately on infusion
    2. Effects cease as soon as infusion is stopped

VI. Dosing

  1. Preparation
    1. Reconstitute 50-100 mg powder in 2-3 ml D5W
    2. Dilute with 250 ml D5W or Normal Saline
    3. Final Concentration: 200-400 mcg/ml
  2. Additional Measures
    1. Wrap solution immediately in aluminum foil
      1. Prevents deterioration under light exposure
    2. Use solution immediately after making it
    3. Discard solution if becomes highly colored
      1. Solution with faint brown tint is still usable
  3. Hypertensive Emergency
    1. Start 0.1 to 0.3 mcg/kg/min (e.g. 6 ml/hour in a 70 kg adult)
    2. Titrate 0.5 to 8.0 ug/kg/min
      1. Carefully monitor hemodynamic parameters
    3. Maximum: 10 mcg/kg/min
      1. Discontinue if inadequate response after 10 minutes
    4. Use lower doses in elderly

VII. Precautions

  1. Small changes in infusion rate result in large changes in Blood Pressure
  2. Significant Hypotension may precipitate secondary events
    1. Myocardial Ischemia or Myocardial Infarction
    2. Cerebral Vascular accident
  3. Avoid Nitroprusside in Coronary Artery Disease
    1. Use Nitroglycerin instead
  4. Thiocyanate Intoxication (cyanide Poisoning)
    1. Rarely seen unless:
      1. Nitroprusside doses over 3 mcg/kg/min (esp. >10 mcg/kg/min)
      2. Prolonged Nitroprusside infusion over 2-3 days
      3. Renal Failure
    2. Monitor blood thiocyanate level
      1. Levels below 10 mg/100 ml are safe
    3. Signs of thiocyanate Intoxication
      1. Tinnitus
      2. Blurred Vision
      3. Altered Level of Consciousness
      4. Nausea
      5. Abdominal Pain
      6. Hyperreflexia
      7. Seizure Disorder

IX. References

  1. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 66-7
  2. Hamilton (2020) Tarascon Pocket Pharmacopoeia

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