What is the recommended dosing for Nitroglycerin (NTG) in the management of angina pectoris?

Nitroglycerin Dosing for Angina Pectoris

Sublingual Nitroglycerin for Acute Anginal Attacks

For acute angina relief, administer 0.3-0.6 mg sublingual nitroglycerin (or 0.4 mg spray) at the first sign of chest discomfort, repeating every 5 minutes for up to 3 doses maximum; if pain persists after the first dose at 5 minutes, the patient must call 9-1-1 immediately before taking additional doses. 1, 2, 3, 4

Acute Dosing Protocol

• Initial dose: Place one 0.3-0.6 mg sublingual tablet (or 0.4 mg spray) under the tongue at symptom onset while sitting or lying down to prevent orthostatic hypotension 1, 2, 4

• Repeat dosing: If symptoms persist, repeat the same dose every 5 minutes 1, 2, 3, 4

• Maximum acute dosing: Up to 3 doses (total 0.9-1.8 mg for tablets or 1.2 mg for spray) over 15 minutes 1, 2, 3, 4

• Emergency threshold: If chest pain is unimproved or worsening after 5 minutes (after the first dose), call 9-1-1 immediately—this indicates possible myocardial infarction requiring emergency evaluation 2, 3, 4

Prophylactic Use Before Exertion

• Timing: Administer one dose 5-10 minutes before activities known to trigger angina 2, 3, 4

• Dose: Same as acute dosing (0.3-0.6 mg sublingual or 0.4 mg spray) 1, 2

Intravenous Nitroglycerin for Refractory Angina

For hospitalized patients with angina unrelieved by 3 sublingual doses, initiate IV nitroglycerin at 5-10 mcg/min via non-PVC tubing, titrating by 10 mcg/min every 3-5 minutes until symptom relief or blood pressure response, with a practical ceiling of 200 mcg/min. 1, 5, 3

IV Titration Protocol

• Starting rate: 5-10 mcg/min via continuous infusion using non-absorbing (non-PVC) tubing to prevent drug adsorption 1, 5, 3

• Initial titration (first 20 minutes): Increase by 10 mcg/min every 3-5 minutes 1, 3

• If no response at 20 mcg/min: Increase increments to 10 mcg/min, then 20 mcg/min as needed 1

• Practical ceiling: 200 mcg/min is commonly used, though prolonged infusions at 300-400 mcg/min for 2-4 weeks have been safely administered without methemoglobin accumulation 1, 3

• Endpoint: Titrate until symptom relief or blood pressure response; if ischemia resolves, no need to continue increasing dose for blood pressure effect alone 1

Long-Acting Nitrate Formulations for Chronic Management

For chronic angina prophylaxis, prescribe long-acting nitrates with mandatory 10-12 hour nitrate-free intervals to prevent tolerance, using either isosorbide mononitrate 60-240 mg once daily (slow-release) or transdermal nitroglycerin 0.2-0.8 mg/hour applied for 12-14 hours then removed. 1, 3

Oral Long-Acting Nitrates

• Isosorbide mononitrate standard: 20 mg twice daily with doses separated by 12-24 hours 1, 3

• Isosorbide mononitrate slow-release: 60-240 mg once daily in the morning 1, 3

• Isosorbide dinitrate standard: 5-80 mg two or three times daily 1, 3

• Isosorbide dinitrate slow-release: 40 mg once or twice daily 1, 3

Transdermal Nitroglycerin

• Dose: 0.2-0.8 mg/hour patch 1, 3

• Application schedule: Apply for 12-14 hours during waking hours, then remove for 10-12 hours overnight to prevent tolerance 1, 3

• Duration of effect: 8-12 hours during intermittent therapy; tolerance develops within 7-8 hours with continuous 24-hour application 1, 6

Critical Safety Contraindications

Nitroglycerin is absolutely contraindicated within 24 hours of sildenafil use or 48 hours of tadalafil use due to risk of life-threatening hypotension, myocardial infarction, and death from synergistic vasodilation via phosphodiesterase inhibition. 1, 2, 4

Absolute Contraindications

• Phosphodiesterase-5 inhibitors: No nitrates within 24 hours of sildenafil or 48 hours of tadalafil; vardenafil timing not established but generally safe after 24 hours 1, 2

• Hypotension: Avoid if systolic blood pressure <90 mmHg or >30 mmHg below baseline 2, 4

• Right ventricular infarction: Nitrates can cause severe hypotension by reducing preload in RV-dependent patients 1

Relative Contraindications and Warnings

• Hypertrophic cardiomyopathy: Nitrates may worsen outflow obstruction and angina 4

• Volume depletion: Use cautiously as hypotension may be accompanied by paradoxical bradycardia and increased angina 4

Common Pitfalls and How to Avoid Them

Tolerance Development

• Mechanism: Continuous nitrate exposure for >10-12 hours daily leads to rapid tolerance, blunting antianginal effects 1, 7, 6

• Prevention: Incorporate mandatory 10-12 hour nitrate-free intervals, typically overnight 1, 3, 7

• Clinical impact: Intermittent dosing maintains efficacy after 1 week, while continuous 24-hour therapy loses effectiveness 6

Rebound Angina During Nitrate-Free Intervals

• Risk: Some patients experience increased anginal frequency during nitrate-free periods, particularly with patch therapy 1, 7

• Management: Schedule nitrate-free intervals during sleep when angina is less likely; consider adding other antianginal agents (beta-blockers, calcium channel blockers) for continuous coverage 1

• Unstable angina exception: Avoid intermittent dosing in acute unstable angina—use continuous IV nitroglycerin with dose escalation to override tolerance 1, 3, 7

Excessive Dosing Complications

• Headache: Severe headaches indicate excessive dosing; reduce dose but recognize headaches may also indicate drug activity 4

• Hypotension with reflex tachycardia: Overdosing causes postural hypotension and paradoxical angina from reflex sympathetic activation 3, 4

• Prevention: Use smallest effective dose; patients should sit or lie down during administration 4

Storage and Potency

• Critical: Keep sublingual tablets in original glass container, tightly capped after each use to prevent potency loss 4

• Unreliable indicator: Burning or tingling sensation under the tongue does not reliably indicate tablet potency 4