What is the time of action for Nitroglycerin (NTG)?

Nitroglycerin Time of Action

Sublingual nitroglycerin has an onset of action within 1 to 3 minutes, with maximum vasodilatory effects occurring by 5 minutes, and effects persisting for at least 25 minutes. 1

Onset and Peak Effect by Route

Sublingual Administration

• Vasodilatory effects begin within 1 to 3 minutes after sublingual administration, with digital plethysmography demonstrating onset as early as 1 minute 1
• Maximum effect is reached by 5 minutes postdose, corresponding with peak plasma concentrations occurring at 6 to 7 minutes 1
• Duration of effect is 1 to 7 minutes for acute symptom relief, though hemodynamic effects persist for at least 25 minutes 2, 1
• Anti-anginal and anti-ischemic effects begin within 2 minutes of sublingual application in exercise-induced angina 3

Intravenous Administration

• Onset is immediate with IV administration, allowing for rapid titration 2
• Effects are dose-dependent and continuous during infusion 4
• Tolerance typically develops after 24 hours of continuous therapy, requiring dose adjustments 5, 4

Pharmacokinetic Profile

Absorption and Distribution

• Absolute bioavailability of sublingual nitroglycerin is approximately 40%, though this varies due to sublingual hydration and mucosal metabolism 1
• Peak plasma concentrations (Cmax) occur at 6 to 7 minutes after sublingual dosing 1
• Volume of distribution is 3.3 L/kg following IV administration 1

Metabolism and Elimination

• Elimination half-life is extremely short at 2 to 3 minutes (range 1.5 to 7.5 minutes), explaining the rapid offset of effects 1
• Clearance (13.6 L/min) greatly exceeds hepatic blood flow, indicating extensive extrahepatic metabolism 1
• Active metabolites (1,2- and 1,3-dinitroglycerin) have peak concentrations at approximately 15 minutes and elimination half-lives of 32 to 36 minutes, contributing to prolonged pharmacologic effects 1

Clinical Dosing Protocol

Acute Angina Management

• Standard dose is 0.3 to 0.6 mg sublingual, most commonly 0.4 mg 6
• May repeat every 5 minutes for up to 3 doses (total 15-minute period) 6
• If symptoms persist after 3 sublingual doses, transition to IV nitroglycerin 2, 6

Intravenous Titration

• Start at 10 mcg/min and increase by 10 mcg/min every 3 to 5 minutes until symptom relief or blood pressure response 2, 4
• At doses above 20 mcg/min, may increase increments to 20 mcg/min for more aggressive titration 4
• Common ceiling is 200 mcg/min, though doses up to 400 mcg/min have been used safely 5, 4

Important Clinical Caveats

Contraindications

• Absolutely contraindicated within 24 hours of sildenafil or 48 hours of tadalafil use due to risk of profound hypotension, MI, and death 2, 6
• **Avoid if systolic blood pressure <90 mmHg** or >30 mmHg below baseline 6, 5

Tolerance Development

• Tolerance develops within 7 to 8 hours with transdermal preparations 2
• Continuous IV infusion produces tolerance after 24 hours, requiring dose escalation or nitrate-free intervals 5, 4