What are the side effects of nitroglycerin?

Side Effects of Nitroglycerin

The most common side effects of nitroglycerin include headache, orthostatic hypotension, dizziness, and flushing, with headache being reported in up to 82% of patients in clinical trials. 1

Common Side Effects

• Headache: The most frequent side effect, often dose-related and reported by up to 82% of patients. Approximately 10% of patients cannot tolerate nitroglycerin due to disabling headaches, though in many patients, headaches are mild to moderate and either resolve or diminish with continued therapy. 1

• Cardiovascular effects:

  • Hypotension (particularly orthostatic/postural) 2
  • Reflex tachycardia 2
  • Flushing 2, 3
  • Palpitations (unusual awareness of heartbeat) 3

• Neurological effects:

  • Dizziness 3
  • Vertigo (balance disorder) 3
  • Weakness 3
  • Fainting, especially when standing up quickly 2, 3

• Gastrointestinal effects:

  • Nausea and vomiting 3

• Other effects:

  • Sweating 3
  • Pallor 3
  • Skin reactions (which may occasionally be severe) 3

Serious Side Effects

• Severe hypotension: The most serious potential complication, which may result in reflex tachycardia and worsening myocardial ischemia. 2

• Aggravated hypoxemia: Nitroglycerin may worsen hypoxemia by increasing ventilation-perfusion mismatch. 2

• Methemoglobinemia: Rarely reported with organic nitrates. Presents as chocolate-brown blood and signs of impaired oxygen delivery despite adequate cardiac output. 3

• Coronary steal: In rare instances, nitroglycerin can cause coronary steal phenomenon and myocardial ischemia. 1

• Nitrate tolerance: Attenuation or loss of the anti-ischemic effect during continuous nitrate medication. 2

• Nitrate rebound: Patients may experience nocturnal anginal episodes during intermittent therapy with nitroglycerin patches. 1

Special Precautions and Contraindications

• Patients with right ventricular infarction: Nitroglycerin should be used with extreme caution or avoided in these patients as they are especially dependent on adequate right ventricular preload to maintain cardiac output and can experience profound hypotension during nitrate administration. 2

• Inferior wall myocardial infarction: Requires careful titration of nitroglycerin due to frequent association with right ventricular infarction. 2

• Phosphodiesterase inhibitors: Nitroglycerin is contraindicated in patients who have recently taken medications for erectile dysfunction:

  • Within 24 hours of sildenafil or vardenafil
  • Within 48 hours of tadalafil 2, 3

• Other contraindications:

  • Recent heart attack 3
  • Severe anemia 2, 3
  • Increased intracranial pressure 2, 3
  • Guanylate cyclase stimulators (e.g., riociguat) 3
  • History of syncope after nitroglycerin administration 1

Risk Factors for Adverse Events

• Age: Increasing age is associated with higher odds of adverse events (OR = 1.02). 4

• Initial vital signs: Higher heart rate (OR = 1.03) and lower systolic blood pressure are associated with increased risk of adverse events. 4

• IV access: Having IV access prior to nitroglycerin administration is associated with fewer adverse events (OR = 0.92). 4

Management of Side Effects

• For hypotension:

  • Discontinue the drug
  • Elevate legs
  • Administer rapid fluid
  • Consider atropine for associated bradycardia 2

• For methemoglobinemia:

  • Intravenous administration of methylene blue (1-2 mg/kg body weight) may be required 3

• For headache:

  • Often resolves or diminishes with continued therapy
  • May require dose adjustment or analgesics 1

• To prevent tolerance:

  • Provide a "nitrate-free interval" each day (typically 10-12 hours)
  • For transdermal patches, remove during part of the day or at night 2

Monitoring Recommendations

• Blood pressure: Regular monitoring is essential, especially when initiating therapy or adjusting doses 2

• Heart rate: Monitor for significant changes, particularly tachycardia or bradycardia 2

• Mental status: Watch for changes that could indicate severe hypotension 4

• Symptoms of overdose: Be alert for persistent throbbing headache, confusion, visual disturbances, dyspnea, diaphoresis, and other signs of excessive vasodilation 3

Remember that adverse events following nitroglycerin administration are relatively rare, especially in patients with systolic blood pressure >110 mmHg and heart rate <100 beats per minute 4. Using the smallest effective dose can help minimize side effects while maintaining therapeutic benefit 2.