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 venous and arterial dilation. This reduces cardiac preload and afterload, thereby decreasing myocardial oxygen demand and improving coronary blood flow to ischemic areas. Available in sublingual tablets, sprays, ointments, transdermal patches, and extended-release capsules, nitroglycerin offers versatile administration routes tailored to both acute attack treatment and prophylactic use. Its rapid onset of action, particularly in sublingual forms, makes it an essential first-line agent for patients with known or suspected coronary artery disease.

Features

• Active pharmaceutical ingredient: Nitroglycerin (Glyceryl trinitrate).
• Available formulations: Sublingual tablets, lingual aerosol spray, topical ointment, transdermal patches, and extended-release oral capsules.
• Rapid onset of action: Sublingual forms typically provide relief within 1 to 3 minutes.
• Multiple strengths: Commonly available as 0.3 mg, 0.4 mg, and 0.6 mg sublingual tablets; 0.4 mg per metered spray; 2% ointment; and patches releasing 0.1 mg/hr to 0.8 mg/hr.
• Stable, light-resistant packaging to protect the drug from degradation.

Benefits

• Provides rapid relief from acute angina pectoris attacks.
• Reduces the frequency and severity of angina episodes when used prophylactically.
• Decreases cardiac workload by lowering preload and afterload, improving myocardial oxygen supply-demand balance.
• Can be used to manage symptoms of congestive heart failure and control blood pressure perioperatively.
• Offers flexible administration methods to suit individual patient needs and lifestyles.
• Empowers patients with a fast-acting, self-administered treatment option, increasing independence and quality of life.

Common use

Nitroglycerin is primarily indicated for the acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease. It is used to manage the pain and discomfort associated with myocardial ischemia. The sublingual tablet and spray formulations are first-line treatments for terminating an acute anginal episode. The ointment and transdermal patch formulations are used for the longer-term, prophylactic prevention of angina attacks. Additionally, intravenous nitroglycerin is used in hospital settings for the management of congestive heart failure, the treatment of hypertensive crises, and to induce controlled hypotension during surgery.

Dosage and direction

Dosage is highly individualized based on the formulation, patient response, and the presence of adverse effects like headache or hypotension. It is crucial to follow the specific prescribing information for each product.

• Sublingual Tablets: At the first sign of an attack, place 1 tablet under the tongue or in the buccal pouch and allow it to dissolve. Dose may be repeated approximately every 5 minutes until pain is relieved. If pain persists after a total of 3 tablets in a 15-minute period, seek emergency medical attention immediately. For prophylaxis, use 5 to 10 minutes before engaging in activities known to cause an attack.
• Lingual Spray: At the first sign of an attack, spray 1 or 2 metered doses onto or under the tongue. Do not inhale the spray. Close mouth immediately after administration. Dose may be repeated every 3 to 5 minutes as needed, up to 3 doses within 15 minutes.
• Ointment: Apply a measured dose (using the supplied applicator paper) to a clean, hairless area of skin (e.g., chest, arm). Do not rub in. Cover with plastic wrap if desired. Rotate application sites to avoid skin irritation. Typically applied every 3 to 8 hours, with a daily 10-12 hour nitrate-free interval to prevent tolerance.
• Transdermal Patch: Apply one patch to a clean, dry, hairless area of skin. Do not apply to distal extremities. Press firmly in place. Rotate application sites. Patches are typically worn for 12-14 hours and removed for 10-12 hours each day to provide a nitrate-free interval and prevent tolerance.

Precautions

• Tolerance: Continuous, 24-hour exposure to nitrates can lead to tolerance (diminished therapeutic effect). A daily nitrate-free interval of 10-12 hours is mandatory for transdermal and ointment formulations.
• Hypotension: Nitroglycerin can cause severe hypotension, especially upon initiation of therapy or after a dose increase. Symptoms include dizziness, lightheadedness, and fainting. This risk is increased in volume-depleted patients or those already taking other antihypertensive agents.
• Headache: A common, often severe, throbbing headache is a frequent side effect, usually diminishing in intensity and frequency with continued therapy. Acetaminophen may be used for management.
• Paradoxical Bradycardia and Angina: Excessive hypotension may lead to a reflex tachycardia. In rare cases, especially with inferior wall MI, it may cause a paradoxical bradycardia and increased angina.
• Use in Specific Populations: Use with caution in patients with hypotension, hypovolemia, inferior wall MI with right ventricular involvement, increased intracranial pressure, or severe anemia. Safety and efficacy in children have not been established.

Contraindications

• Known hypersensitivity to nitroglycerin, other nitrates, or any component of the formulation.
• Concomitant use with phosphodiesterase type 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.
• Patients with severe anemia.
• Increased intracranial pressure (e.g., following head trauma or cerebral hemorrhage).
• Circulatory failure and shock states.
• Constrictive pericarditis and cardiac tamponade.
• Nitrate therapy is contraindicated in patients with known inadequate cerebral circulation.

Possible side effect

The most common side effect is headache, which may be severe. Other frequently reported side effects include:

• Hypotension (dizziness, lightheadedness, syncope)
• Reflex tachycardia
• Flushing
• Nausea and vomiting
• Weakness
• Dermatitis and skin irritation (with topical formulations)
• Less common but serious side effects requiring medical attention:
  • Severe or persistent hypotension
  • Worsening angina symptoms
  • Methemoglobinemia (symptoms include cyanosis, dyspnea, fatigue; risk is higher with overdose)
  • Allergic reactions (rash, itching, swelling)

Drug interaction

• Phosphodiesterase-5 (PDE-5) Inhibitors (e.g., Sildenafil, Tadalafil, Vardenafil): Absolute Contraindication. Concomitant use can cause severe, potentially fatal hypotension. A minimum separation of 24 hours (48 hours for tadalafil) is required.
• Soluble Guanylate Cyclase (sGC) Stimulators (e.g., Riociguat): Absolute Contraindication. Risk of symptomatic hypotension.
• Antihypertensive Agents (e.g., Beta-blockers, ACE inhibitors, Calcium channel blockers, Diuretics): Additive hypotensive effects. Blood pressure must be monitored closely.
• Alcohol: Potentiates the vasodilatory and hypotensive effects of nitroglycerin.
• Dihydroergotamine: Nitroglycerin may potentiate the vasoconstrictive effects of dihydroergotamine, increasing the risk of ergotism.
• Aspirin: Coadministration may increase nitroglycerin plasma concentrations.
• Heparin: Intravenous nitroglycerin has been reported to reduce the anticoagulant effect of heparin. Monitor activated partial thromboplastin time (aPTT).

Missed dose

This applies primarily to scheduled prophylactic formulations (ointment, patches).

• Ointment/Transdermal Patch: Apply the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and resume the usual dosing schedule. Do not apply extra ointment or a second patch to make up for a missed dose, as this increases the risk of hypotension and overdose.

Overdose

Nitroglycerin overdose is characterized by severe hypotension, throbbing headache, vertigo, palpitations, visual disturbances, flushing, perspiration, nausea and vomiting, syncope, methemoglobinemia (with cyanosis, dyspnea, and anxiety), and even death.

• Treatment: Management is primarily supportive. Place the patient in a recumbent position with legs elevated to maximize venous return. Administer intravenous fluids for volume expansion. If methemoglobinemia is present and symptomatic (e.g., cyanosis unresponsive to oxygen), methylene blue 1-2 mg/kg IV is the specific antidote. Alpha-adrenergic agonists (e.g., phenylephrine) may be considered for refractory hypotension, but epinephrine is not recommended as it may exacerbate ischemia. Remove any topical product from the skin.

Storage

• Sublingual Tablets: Store in the original glass container. Keep tightly closed. Protect from light, moisture, and heat. Do not store in bathroom or kitchen. Do not transfer to other containers (e.g., cotton-stoppered bottles or plastic pill organizers), as this leads to rapid loss of potency. Replace supply every 6 months after opening the bottle.
• Lingual Spray: Store at room temperature. Do not expose to extreme heat or open flame.
• Ointment & Patches: Store at room temperature. Keep ointment tube tightly closed.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It 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 medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision and are not liable for any damages or negative consequences from any treatment, action, application, or preparation, to any person reading or following the information in this document.

Reviews

• “As a cardiologist with over 20 years of experience, nitroglycerin remains an indispensable tool in our arsenal. Its rapid action in aborting acute angina attacks is unmatched. Patient education on proper use and the critical nitrate-free interval for prophylactic forms is paramount for long-term efficacy.” – Dr. A. Sharma, MD, FACC
• “This medication has given me my life back. Knowing I have the spray in my pocket allows me to garden and walk my dog without the constant fear of crippling chest pain. The headaches were intense at first but have lessened significantly.” – Verified Patient
• “From a clinical pharmacy perspective, the drug interaction with PDE-5 inhibitors is the most critical counseling point. Ensuring patients understand this absolute contraindication is a matter of patient safety and can be life-saving.” – Clinical Pharmacist, BCOP
• “The development of tolerance with continuous use is a significant pharmacological consideration that all prescribers must be aware of. Adherence to a dosing schedule that incorporates a nitrate-free period is non-negotiable for maintaining therapeutic benefit.” – Professor of Pharmacology