What is the protocol for trialing nitrates (nitroglycerin) in patients with angina?

Protocol for Trialing Nitrates in Angina

For acute anginal attacks, administer sublingual nitroglycerin 0.3-0.6 mg at the first sign of chest pain, repeating every 5 minutes for up to 3 doses (15 minutes total); if pain persists or differs from typical angina after 3 tablets, seek immediate medical attention as this may represent myocardial infarction. 1

Acute Angina Management

Sublingual Nitroglycerin Protocol

• Dissolve one tablet (0.3-0.6 mg) under the tongue at the first sign of anginal pain 1
• Patient should sit down during administration to prevent falls from lightheadedness or hypotension 1
• Repeat dosing every 5 minutes if pain persists, up to a maximum of 3 tablets in 15 minutes 1
• Alternative: NTG spray 0.4 mg as needed, with similar efficacy to sublingual tablets 2, 3
• Onset of action: 1-7 minutes 2

Critical Safety Checkpoints Before Administration

• Contraindicated if systolic blood pressure <90 mmHg or ≥30 mmHg below baseline 2
• Absolute contraindication: sildenafil use within 24 hours, tadalafil within 48 hours (risk of profound hypotension, MI, or death) 2
• Avoid in marked bradycardia or tachycardia 2
• Use caution in volume-depleted or already hypotensive patients 1

Prophylactic Use

• Administer 5-10 minutes before activities known to precipitate angina 1
• This "situational prophylaxis" is highly effective for preventing predictable anginal episodes 2

Intravenous Nitroglycerin for Refractory Angina

Initiation Protocol

For patients with ongoing ischemic symptoms unresponsive to sublingual NTG and beta-blockers, start IV nitroglycerin at 10 mcg/min via continuous infusion through non-absorbing tubing. 2, 3

Titration Algorithm

• Increase by 10 mcg/min every 3-5 minutes until symptom relief or blood pressure response 2
• If no response at 20 mcg/min, use larger increments (10 mcg/min, then 20 mcg/min) 2
• Stop dose escalation once symptoms resolve—no need to continue titrating for blood pressure effect alone 2
• If symptoms persist, continue increasing until blood pressure response observed, then reduce increment size and lengthen intervals 2

Blood Pressure Targets During Titration

• Do not reduce systolic BP below 110 mmHg in normotensive patients 2
• In hypertensive patients, do not reduce mean arterial pressure >25% from baseline 2
• Typical ceiling dose: 200 mcg/min (though doses up to 300-400 mcg/min are safe) 2

Long-Acting Nitrate Therapy

Formulations and Dosing

Long-acting nitrates are acceptable for patients requiring chronic antianginal therapy without ongoing refractory symptoms, but MUST include a daily nitrate-free interval of 10-12 hours to prevent tolerance. 2, 3, 4

• Isosorbide dinitrate (ISDN): 5-80 mg, 2-3 times daily (duration up to 8 hours) 2
• Isosorbide mononitrate (ISMN): 20 mg twice daily with asymmetric dosing (duration 12-24 hours) 2, 4
• ISMN extended-release: 60-240 mg once daily in morning 2, 4
• Transdermal NTG: 0.2-0.8 mg/hour applied for 12-14 hours, then removed for 10-12 hours overnight 2, 4

Critical Tolerance Prevention Strategy

• Tolerance develops after 24 hours of continuous therapy with any formulation 2, 4
• The nitrate-free interval (10-12 hours daily) is mandatory to maintain efficacy 3, 4
• Continuous 24-hour nitrate coverage is NOT achievable without tolerance 2, 5
• Provide sublingual NTG for breakthrough angina during nitrate-free intervals 4

Transitioning from IV to Oral Nitrates

Conversion Protocol

When patients have been free of ischemic symptoms for 12-24 hours on IV NTG, attempt dose reduction and conversion to oral or topical nitrates. 2

• Do not continue IV NTG in patients who remain symptom-free 2
• Use gradual dose reduction—abrupt cessation can cause rebound ischemic ECG changes 2, 4
• Convert within 24 hours in stabilized patients to non-tolerance-producing oral regimens 2

Managing Tolerance During IV Therapy

• If ischemia recurs during continuous IV NTG (>24 hours), increase dose to restore responsiveness 2
• After symptom control, attempt to add a nitrate-free interval even with IV therapy 2, 4

Common Pitfalls and How to Avoid Them

Recognizing Treatment Failure

• If pain persists after 3 sublingual tablets (15 minutes) or differs from typical angina, this represents potential MI—activate emergency protocols immediately 1
• Short-acting nitrate consumption serves as a useful measure of treatment efficacy with other antianginal drugs 2

Side Effects Management

• Headache is dose-dependent and common; may indicate drug activity 2, 1
• Hypotension may be accompanied by paradoxical bradycardia and increased angina 1
• Excessive dosing can cause postural hypotension with reflexogenic tachycardia leading to "paradoxical" angina 2

Storage and Potency

• Keep sublingual NTG in original glass container, tightly capped after each use to prevent potency loss 1
• The burning/tingling sensation under the tongue is NOT a reliable indicator of tablet potency 1

Special Populations

• Nitrate therapy may aggravate angina in hypertrophic cardiomyopathy 1
• No dosage adjustment required in renal failure 1

Drug Interactions

• Tricyclic antidepressants and anticholinergics cause dry mouth, impairing sublingual dissolution—consider chewing gum or artificial saliva 1
• Aspirin may enhance vasodilatory effects 1
• Alcohol potentiates hypotensive effects 1