II. History

  1. Albert Nobel stabilized Nitroglycerin for dynamite
    1. Some postulate that he died of Nitroglycerin toxicity

III. Medications

  1. Short Acting Nitroglycerin (Sublingual Nitroglycerin)
    1. Peak Levels: 1-2 minutes
    2. Duration: 30 to 60 minutes
  2. Long Acting Nitroglycerin (Isosorbide Dinitrate)
    1. Onset: 5 minutes for sublingual (30 minutes oral)
    2. Duration: 1 to 4 hours for sublingual (4-6 hours for oral, 8 hours for sustained release)
  3. Intravenous Nitroglycerin
    1. Onset in 2 minutes
    2. Duration 3 to 5 minutes
  4. Transdermal Nitroglycerin
    1. Peak levels: 30 to 60 minutes
    2. Duration: 12-14 hours per day (until patch removed)
  5. Nitroglycerin Paste (Ointment)
    1. Onset: 1 hour
    2. Duration: 2 to 12 hours

V. Contraindications

  1. Aortic Stenosis
  2. Pulmonary Hypertension
  3. Hypotension
    1. Avoid when systolic Blood Pressure <90 to 100 mmHg or more than 30 mmHg below baseline
    2. Hypotension due to nitrates is typically transient after single doses and responds to small fluid boluses
  4. Phosphodiesterase Inhibitor (e.g. Sildenafil, Tadalafil, Vardenafil)
  5. Guanylate Cyclase Simulator (Riociguat)
  6. Restrictive Cardiomyopathy (or Pericardial Tamponade, constrictive Pericarditis)
  7. Right sided Myocardial Infarction (subtype of inferior Myocardial Infarction)
    1. Caution in inferior STEMI with ST Elevation in V1 and ST depression in V2
    2. Hypertensive patients with MI, regardless of distribution, are unlikely to have adverse effects with Nitroglycerin
    3. Little evidence to support a broad avoidance of nitrates in inferior MI in normotensive or hypertensive patients
      1. Wilkinson-stokes (2023) Emerg Med J 40(2): 108-13 [PubMed]

VI. Mechanism

  1. Relaxes vascular Smooth Muscle
  2. Venous Dilation (more than Nitroprusside)
    1. Inhibits venous return (Preload)
      1. Decreases intra-myocardial wall tension
      2. Decreases intraventricular work
    2. Reduces left ventricular filling pressure
      1. Decreases myocardial oxygen demand
      2. Reduces Myocardial Ischemia
    3. Cardiac Output
      1. Increased in Congestive Heart Failure
      2. Decreased or normal if no Heart Failure
  3. Arterial Dilation (less than Nitroprusside)
    1. Relieves Angina
    2. Dilates large coronary arteries
    3. Antagonizes vasospasm
    4. Increases coronary collateral Blood Flow
      1. Increases perfusion to ischemic Myocardium
    5. Decreases Systemic Vascular Resistance
  4. Esophageal Spasm also responds to nitrates
    1. Pain relief with Nitroglycerin is not always Angina

VII. Drug Interactions

  1. Phosphodiesterase Inhibitors (e.g. Sildenafil, Tadalafil, Vardenafil)
    1. Profound hypotensive reaction
    2. Do not use with Nitroglycerin!
    3. Nitrates may be used >24 hours after Sildenafil or vardenafil or >48 hours after Tadalafil
  2. Guanylate Cyclase Simulator (Riociguat)
  3. Tissue Plasminogen Activator (Alteplase, tPA)
    1. IV Nitroglycerin may reduce plasma concentrations
  4. Heparin
    1. IV Nitroglycerin may reduce Anticoagulant response

VIII. Adverse Effects

  1. Headache
  2. Methemoglobinemia
  3. Hypoxemia (Ventilation-perfusion mismatch)
  4. Hypotension
    1. Risk Factors
      1. Aortic Stenosis
      2. Pulmonary Hypertension
      3. Hypovolemia
      4. PDE5 Inhibitor (e.g. Sildenafil)
      5. Right-sided Myocardial Infarction
    2. Prevention
      1. Administer Intravenous Fluid bolus
      2. Reduce Nitrate dose
      3. Consider Atropine if Bradycardia present
  5. Rebound Tachycardia
  6. Peripheral Edema

IX. Safety

  1. Pregnancy Category C
  2. Unknown safety in Lactation

X. References

  1. Orman and Mattu in Herbert (2017) EM:Rap 17(7): 6-7
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 70-1

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Cost: Medications

nitroglycerin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
NITROGLYCERIN 0.1 MG/HR PATCH Generic $0.48 each
NITROGLYCERIN 0.2 MG/HR PATCH Generic $0.54 each
NITROGLYCERIN 0.3 MG TABLET SL Generic $0.14 each
NITROGLYCERIN 0.4 MG TABLET SL Generic $0.13 each
NITROGLYCERIN 0.4 MG/HR PATCH Generic $0.68 each
NITROGLYCERIN 0.6 MG TABLET SL Generic $0.21 each
NITROGLYCERIN 0.6 MG/HR PATCH Generic $0.78 each
NITROGLYCERIN 400 MCG SPRAY Generic $17.06 per gram