How do I prepare nitroglycerin, what are the appropriate doses for each route of administration, and what are its clinical indications?

Nitroglycerin Preparation, Dosing, and Indications

Preparation and Administration Routes

Nitroglycerin requires no preparation for sublingual or spray formulations—these are ready-to-use; intravenous nitroglycerin must be administered through non-absorbing tubing via continuous infusion pump. 1

Sublingual/Spray (Immediate Use)

• Sublingual tablets: Available in 0.3 mg, 0.4 mg, and 0.6 mg strengths—no preparation needed, place directly under tongue 1, 2
• Sublingual spray: 0.4 mg per actuation—spray directly under tongue, no preparation required 1
• Onset of action: 1-7 minutes with effects persisting at least 25 minutes 1, 2, 3

Intravenous (Requires Setup)

• Must use non-absorbing tubing to prevent drug loss through standard IV tubing 1
• Prepare as continuous infusion with concentration appropriate for infusion pump 1
• Immediate onset allowing rapid titration 3

Transdermal (Apply to Skin)

• Patches: 0.2-0.8 mg/hour—apply to clean, dry, hairless skin 1
• Must remove after 12 hours daily to prevent tolerance, then reapply new patch after 12-hour nitrate-free interval 1, 3, 4
• Onset 8-12 hours, tolerance develops within 7-8 hours of continuous use 1, 3

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Dosing by Route and Clinical Scenario

Acute Angina (Sublingual/Spray)

Standard dose is 0.4 mg sublingual, repeated every 5 minutes up to 3 doses maximum. 1, 2

• First dose: 0.3-0.6 mg (most commonly 0.4 mg) sublingual 1, 2
• Repeat dosing: May repeat every 5 minutes for maximum of 3 doses 1, 2
• Call 9-1-1 if: Pain unimproved or worsening after first dose at 5 minutes 1
• Maximum single dose: Up to 1.5 mg 1, 2

Persistent Angina/ACS (Intravenous)

Start IV nitroglycerin at 10 mcg/min and increase by 10 mcg/min every 3-5 minutes until symptom relief or blood pressure response. 1, 3

• Initial rate: 10 mcg/min via continuous infusion 1, 3
• Titration protocol: Increase by 10 mcg/min every 3-5 minutes 1, 3
• If no response at 20 mcg/min: Use 10 mcg/min increments, then advance to 20 mcg/min increments 1
• Practical ceiling: 200 mcg/min commonly used, though doses up to 300-400 mcg/min are safe 1, 5
• Tolerance: Develops after 7-8 hours of continuous infusion, may require dose escalation 1, 3, 5

Chronic Stable Angina Prevention (Oral/Transdermal)

• Isosorbide mononitrate: 20 mg twice daily with dosing interval to provide nitrate-free period 1, 5
• Isosorbide dinitrate: 5-80 mg 2-3 times daily 1, 5
• Transdermal patch: 0.2-0.8 mg/hour applied for 12 hours, then removed for 12 hours 1, 5

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Clinical Indications

Primary Indications

Nitroglycerin is indicated for acute angina relief, unstable angina/NSTEMI with ongoing ischemia, and acute decompensated heart failure with hypertension. 1

• Acute anginal episodes: Sublingual/spray for immediate symptom relief 1, 2
• Unstable angina/NSTEMI: IV therapy when symptoms persist after 3 sublingual doses 1, 2, 3
• ACS with hypertension: IV nitroglycerin for blood pressure control and ischemia relief 1, 5
• Acute pulmonary edema (SCAPE): High-dose IV nitroglycerin (up to 200-400 mcg/min) for afterload reduction 5
• Chronic stable angina prophylaxis: Long-acting oral nitrates or transdermal patches with nitrate-free intervals 1, 4

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Critical Contraindications and Safety Parameters

Absolute Contraindications

Never administer nitroglycerin within 24 hours of sildenafil/vardenafil or 48 hours of tadalafil—this combination causes profound hypotension, MI, and death. 1, 2, 3

• Phosphodiesterase-5 inhibitors: Contraindicated within 12 hours of avanafil, 24 hours of sildenafil/vardenafil, 48 hours of tadalafil 1, 3
• Hypotension: Avoid if systolic BP <90 mmHg 1, 2
• Excessive BP drop: Do not use if systolic BP >30 mmHg below baseline 1, 3
• Right ventricular infarction: Contraindicated due to preload dependence 1, 5

Blood Pressure Targets During IV Therapy

• Normotensive patients: Do not reduce systolic BP below 110 mmHg 1, 5
• Hypertensive patients: Do not reduce mean arterial pressure >25% below baseline 5
• Monitor continuously during IV infusion and dose adjustments 5

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Common Pitfalls and How to Avoid Them

Tolerance Development

Continuous nitroglycerin exposure for >24 hours causes tolerance—prevent this by providing 10-12 hour nitrate-free intervals daily. 1, 3, 4, 6

• Remove transdermal patches after 12 hours, reapply after 12-hour break 1, 5, 4
• For IV therapy >24 hours, expect tolerance and need for dose escalation 3, 5
• Transition to intermittent oral/transdermal therapy once stable 5, 6

Rebound Ischemia with Abrupt Discontinuation

Never stop IV nitroglycerin abruptly—taper by 5-10 mcg/min every 3-5 minutes while monitoring for ECG changes. 5

• Ensure patient symptom-free for 12-24 hours before tapering 5
• Start oral/transdermal nitrate 1-2 hours before discontinuing IV to ensure therapeutic overlap 5
• Watch for worsening ischemic ECG changes during taper 5

Drug Interaction Catastrophe

Always ask about erectile dysfunction medications before giving any nitrate—the combination is lethal. 1, 3

• Document PDE5 inhibitor use and timing in every chest pain patient 1
• Wait full 24-48 hours (drug-dependent) before administering nitrates 1, 3
• Educate patients never to combine these medications 1, 3

Hypotension in Right Ventricular Infarction

Suspect RV infarction in inferior MI—nitrates cause catastrophic hypotension in these preload-dependent patients. 1, 5

• Obtain right-sided ECG leads (V4R) in all inferior STEMIs before giving nitrates 5
• Avoid nitrates if ST elevation in V4R or clinical signs of RV involvement 5