Nitroglycerin is a cornerstone medication in the management of angina pectoris, a condition characterized by chest pain due to myocardial ischemia. As an organic nitrate vasodilator, its primary mechanism of action involves the relaxation of vascular smooth muscle, leading to a reduction in cardiac preload and afterload. This decreases myocardial oxygen demand while simultaneously improving coronary blood flow to ischemic regions of the heart. Available in multiple formulations—including sublingual tablets, sprays, ointments, and transdermal patches—nitroglycerin offers flexibility in administration tailored to both acute symptomatic relief and prophylactic use. Its rapid onset of action, particularly in sublingual forms, makes it an indispensable agent for patients experiencing acute anginal attacks, providing prompt symptom alleviation and improving functional capacity.

Features

• Active pharmaceutical ingredient: Glyceryl trinitrate.
• Available formulations: Sublingual tablets, lingual spray, topical ointment, transdermal patches, and extended-release capsules.
• Rapid onset of action: Sublingual forms typically provide relief within 1 to 3 minutes.
• Multiple administration routes allow for tailored therapeutic regimens (acute vs. prophylactic).
• Chemical stability is maintained in original, light-resistant containers.

Benefits

• Provides rapid symptomatic relief from acute anginal attacks, reducing chest pain and associated anxiety.
• Decreases myocardial oxygen demand through venodilation and arterial vasodilation, improving the heart’s efficiency.
• Can be used prophylactically to prevent angina episodes triggered by predictable exertion or stress.
• Enhances coronary blood flow by dilating epicardial coronary arteries and collateral vessels.
• Offers formulation flexibility to suit individual patient needs, lifestyles, and clinical scenarios.
• Well-established efficacy and safety profile backed by decades of clinical use and research.

Common use

Nitroglycerin is primarily indicated for the treatment and prevention of angina pectoris. Its use is central to the management of both stable effort-induced angina and unstable angina. In acute settings, the sublingual tablet or spray is used to abort an ongoing anginal attack. For prophylactic purposes, patients may use it shortly before engaging in activities known to precipitate angina (e.g., physical exertion, sexual activity). Topical ointments and transdermal patches are utilized for longer-term prophylaxis in patients with frequent angina episodes, providing a sustained vasodilatory effect. Off-label, it is sometimes used in acute care settings for the management of hypertensive emergencies, acute coronary syndromes under careful monitoring, and even in cases of acute pulmonary edema due to its potent preload-reducing effects.

Dosage and direction

Dosage is highly formulation-dependent and must be individualized based on patient response, tolerance, and clinical indication.

• Sublingual Tablets: At the first sign of an anginal attack, place one tablet (typically 0.3 mg or 0.4 mg) under the tongue or in the buccal pouch. Allow it to dissolve completely without swallowing. Dose may be repeated every 5 minutes for a maximum of 3 tablets within a 15-minute period. If pain persists after 3 doses, seek emergency medical attention immediately.
• Lingual Spray: Spray 1 or 2 metered doses (0.4 mg each) onto or under the tongue. Do not inhale the spray. Close mouth immediately after administration. Do not rinse mouth for 5-10 minutes. The same repeating protocol as for tablets applies.
• Topical Ointment (2%): Apply a measured dose (using the supplied paper applicator) to a clean, dry, hairless area of skin. The initial dose is typically 1/2 inch (15 mg), titrated upward as needed. The usual dosage range is 1/2 to 2 inches (15 to 60 mg) every 8 hours. Rotate application sites to prevent skin irritation. Do not apply to distal extremities.
• Transdermal Patches: Apply one patch to a clean, dry, hairless area of the torso or upper arm. The initial dose is often 0.2 mg/hr. Patches are typically worn for 12-14 hours and removed for a 10-12 hour nitrate-free interval each day to prevent tolerance.
• General Direction: Always sit down before taking a dose due to the risk of hypotension and dizziness. Do not chew or swallow sublingual forms.

Precautions

• Tolerance: Continuous exposure to nitrates can lead to the rapid development of pharmacological tolerance, diminishing the anti-anginal and hemodynamic effects. A daily nitrate-free interval of 10-12 hours is mandatory for patients on long-acting formulations (patches, ointments) to maintain efficacy.
• Hypotension: Nitroglycerin can cause severe hypotension, manifesting as dizziness, lightheadedness, or syncope, especially upon initiation or dose escalation. This risk is potentiated by alcohol, other vasodilators, and volume depletion.
• Headache: A pronounced, throbbing headache is a very common side effect due to cerebral vasodilation. It often diminishes in intensity with continued therapy. Use of analgesics like acetaminophen may be appropriate; consult a physician.
• Paradoxical Bradycardia and Angina: Excessive hypotension may provoke a reflex tachycardia. Conversely, in rare cases, severe hypotension can lead to bradycardia and worsened angina.
• Conditional Use: Use with extreme caution, if at all, in patients with inferior wall MI who may be dependent on preload, or in those with suspected right ventricular infarction. Caution is also advised in patients with increased intracranial pressure, low systolic blood pressure (<90 mmHg), or severe anemia.
• Storage: Protect from light, moisture, and heat. Sublingual tablets lose potency rapidly once the bottle is opened; they should be replaced every 3-6 months or as specified by the manufacturer.

Contraindications

• Concomitant use with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) or soluble guanylate cyclase (sGC) stimulators (e.g., riociguat). This combination can cause profound, life-threatening hypotension.
• Known hypersensitivity or idiosyncratic reaction to nitroglycerin, other nitrates, or nitrites.
• Severe anemia.
• Increased intracranial pressure (e.g., following head trauma, cerebral hemorrhage).
• Circulatory failure and shock states, including cardiogenic shock.
• Marked hypotension (systolic blood pressure <90 mmHg).
• Constructive pericarditis and cardiac tamponade.

Possible side effect

The most common side effects are directly related to its vasodilatory pharmacology.

• Very Common (>10%): Headache (often dose-related and persistent), dizziness, lightheadedness, orthostatic hypotension, flushing.
• Common (1-10%): Tachycardia, palpitations, nausea, vomiting, weakness, syncope (fainting).
• Uncommon (0.1-1%): Dermatitis or contact sensitization with topical forms, dry mouth, rash, pruritus at application site (patches/ointment).
• Rare (<0.1%): Methemoglobinemia (especially with high doses or overdose), blurred vision, diaphoresis (excessive sweating), severe hypotension leading to cardiovascular collapse, paradoxical angina pectoris, exfoliative dermatitis.

Drug interaction

Nitroglycerin has significant and potentially dangerous interactions with several drug classes.

• Phosphodiesterase-5 Inhibitors (e.g., Sildenafil, Tadalafil, Vardenafil): CONTRAINDICATED. Concomitant use can cause severe, potentially fatal hypotension. A minimum separation of 24 hours (48 hours for tadalafil) is required.
• Other Vasodilators (e.g., other nitrates, calcium channel blockers, ACE inhibitors, ARBs, alpha-blockers): Additive hypotensive effects. Blood pressure must be monitored closely.
• Antihypertensive Agents: Enhanced blood pressure-lowering effect.
• Alcohol: Potentiates vasodilation and hypotension.
• Dihydroergotamine: Nitroglycerin may increase the bioavailability of dihydroergotamine, increasing the risk of ergotism.
• Heparin: There is some evidence that IV nitroglycerin may partially counteract the anticoagulant effect of heparin, requiring more frequent monitoring of activated partial thromboplastin time (aPTT).
• Aspirin: Coadministration may increase nitroglycerin serum concentrations.

Missed dose

The protocol for a missed dose depends entirely on the formulation.

• Sublingual Tablets/Spray (PRN for acute attacks): This is an “as-needed” medication. There is no scheduled dose to miss. Use it at the onset of angina symptoms.
• Scheduled Dosing (Ointment, Patches): If a dose is missed and it is almost time for the next scheduled dose, skip the missed dose and resume the usual dosing schedule. Do not double the dose to make up for the missed one. Applying extra ointment or an extra patch can lead to dangerous hypotension and overdose. Adhere strictly to the prescribed nitrate-free interval for patches.

Overdose

Nitroglycerin overdose is a medical emergency characterized by severe, life-threatening hypotension and its sequelae.

• Signs and Symptoms: Profound hypotension with weak, thready pulse; syncope; persistent, throbbing headache; dizziness; palpitations; visual disturbances; flushing; diaphoresis (cold sweat); nausea and vomiting; cyanosis with methemoglobinemia (chocolate-brown colored blood, hypoxia that does not respond to oxygen administration); syncope; seizures; coma; cardiovascular collapse; and death.
• Management: Immediately remove any topical formulations. Place the patient in a supine position with legs elevated to maximize venous return. Administer IV fluids for volume expansion. In cases of severe hypotension, alpha-adrenergic agonists (e.g., phenylephrine) may be required. Avoid epinephrine and other mixed alpha-beta agonists, as beta-2 mediated vasodilation could worsen hypotension. For methemoglobinemia (>30% or symptomatic), the antidote is methylene blue, administered slowly IV at 1-2 mg/kg over 5 minutes. Provide standard supportive care, including oxygen and hemodynamic monitoring.

Storage

Proper storage is critical to maintain the drug’s chemical stability and potency.

• Store at controlled room temperature (20°-25°C or 68°-77°F). Avoid excessive heat and moisture.
• Sublingual Tablets: Keep in the original glass bottle with the metal cap screwed on tightly. The bottle must be light-resistant. Do not transfer tablets to other containers (e.g., pill organizers). Replace the supply every 3-6 months after opening, as the drug volatilizes and loses potency.
• Lingual Spray: Does not require refrigeration. Protect from light.
• Ointment and Patches: Store at room temperature. Keep the tube of ointment tightly closed.

Disclaimer

This information is for educational and informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting, stopping, or changing any medication regimen. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content provided reflects historical and general medical knowledge and may not encompass the latest research or be applicable to your specific individual health situation.

Reviews

• “As a cardiologist with over 30 years of practice, nitroglycerin remains the gold standard for immediate relief of anginal pain. Its rapid action is unparalleled. The key is proper patient education on administration and the critical importance of the nitrate-free interval to prevent tolerance.” – Dr. A. Reynolds, MD, FACC
• “Managing my stable angina would be impossible without nitroglycerin spray. It’s discreet, acts within a minute, and gives me the confidence to engage in daily activities. The headaches were intense at first but have lessened over time.” – Verified Patient
• “From a clinical pharmacy perspective, the most crucial counseling points for nitroglycerin are the absolute contraindication with PDE-5 inhibitors and the proper storage of sublingual tablets. Patient understanding of these two factors is paramount for safety.” – Clinical Pharmacist, Major Hospital System
• “The development of transdermal patches was a significant advancement for prophylaxis. It allows for consistent control of angina symptoms, though the requirement for a daily drug holiday can be confusing for some patients and requires clear communication.” – Cardiac Nurse Practitioner