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 is 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, and transdermal patches, nitroglycerin offers both immediate relief from acute angina attacks and prophylactic protection against anticipated episodes. Its rapid onset and well-established efficacy profile make it an indispensable tool in both outpatient and emergency cardiac care.

Features

• Active Pharmaceutical Ingredient: Glyceryl trinitrate.
• Pharmacological Class: Organic nitrate vasodilator.
• Available Formulations: Sublingual tablets, lingual spray, topical ointment, transdermal patches, and extended-release capsules.
• Mechanism of Action: Metabolized to release nitric oxide (NO), which activates guanylyl cyclase, increasing cyclic guanosine monophosphate (cGMP) leading to vasodilation.
• Onset of Action: Sublingual/Spray: 1 to 3 minutes; Ointment/Patch: 30 to 60 minutes.
• Duration of Action: Sublingual/Spray: 30 to 60 minutes; Ointment: 4 to 8 hours; Patch: 8 to 14 hours (depending on patch type and wear time).
• Prescription Status: Prescription-only medication in most jurisdictions.

Benefits

• Provides rapid relief from the pain and discomfort of acute angina pectoris attacks.
• Reduces cardiac workload by decreasing preload (venous dilation) and afterload (arterial dilation), improving the heart’s efficiency.
• Can be used prophylactically to prevent angina episodes triggered by physical exertion or emotional stress.
• Offers flexible administration routes to suit individual patient needs and lifestyles.
• Has a long history of clinical use with a well-understood safety and efficacy profile.
• Contributes to improved quality of life by allowing patients greater physical activity with reduced fear of an angina attack.

Common use

Nitroglycerin is primarily indicated for the treatment and prevention of angina pectoris due to coronary artery disease. Its use is categorized into two main approaches:

1. Acute Relief: Sublingual tablets or spray are used at the first sign of an angina attack to abort the episode.
2. Prophylaxis: Ointments, patches, or extended-release formulations are used on a scheduled basis to provide a sustained effect, preventing angina attacks that are predictable (e.g., with physical activity). It may also be used in hospital settings for the management of congestive heart failure and perioperative hypertension.

Dosage and direction

Dosage is highly individualized. Always follow the specific instructions provided by the prescribing physician.

• 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 completely. Do not swallow. Dose may be repeated every 5 minutes for a maximum of 3 tablets in 15 minutes. If pain persists after 3 doses, seek emergency medical attention immediately.
• Lingual Spray: Spray 1 or 2 doses onto or under the tongue. Do not inhale. Close mouth immediately after use. Do not rinse for 5-10 minutes. The same 15-minute/3-dose rule applies as with tablets.
• Ointment: Apply the prescribed amount (typically measured using the supplied paper applicator) to a clean, hairless area of skin (e.g., chest, arm, thigh). Do not rub in. Cover with plastic wrap. Rotate application sites to avoid skin irritation.
• Transdermal Patch: Apply one patch to a clean, dry, hairless area of skin. Press firmly in place. Adhere to a strict “patch-on” and “patch-off” schedule (e.g., on for 12-14 hours, off for 10-12 hours) to prevent tolerance. Rotate application sites.

Precautions

• Tolerance: Continuous exposure to nitrates can lead to tolerance, diminishing the drug’s hemodynamic and antianginal effects. A daily nitrate-free interval (e.g., 10-12 hours for patches) is mandatory to prevent this.
• Hypotension: Nitroglycerin can cause severe hypotension, especially upon initiation or dose increase. This risk is heightened in volume-depleted patients or those already taking other antihypertensive agents. Symptoms include dizziness, lightheadedness, and syncope, particularly upon standing (orthostatic hypotension).
• Headache: A common side effect, often throbbing, is a marker of vasodilation. It typically diminishes in frequency and severity with continued therapy. Use of analgesics like acetaminophen may be appropriate; consult a physician.
• Withdrawal: Abrupt discontinuation of chronic nitrate therapy can precipitate rebound angina or ischemia. Doses should be tapered under medical supervision.
• Specific Populations: Use with extreme caution in patients with hypotension, hypovolemia, inferior wall MI with right ventricular involvement, or increased intracranial pressure (e.g., after head trauma or cerebral hemorrhage).

Contraindications

• Known hypersensitivity to nitroglycerin, other nitrates, or any component of the formulation.
• Concurrent 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.
• Patients with severe anemia.
• Increased intracranial pressure.
• Circulatory failure and shock states.
• Conditions associated with hypoxemia (e.g., severe respiratory failure).
• Constructive pericarditis and cardiac tamponade.

Possible side effect

Common side effects are primarily related to vasodilation and are often dose-dependent:

• Headache (most common, may be severe)
• Dizziness, lightheadedness, vertigo
• Orthostatic hypotension
• Tachycardia or reflex tachycardia
• Flushing
• Nausea, vomiting Less common but serious side effects requiring medical attention:
• Severe or persistent hypotension
• Syncope (fainting)
• Worsening angina symptoms
• Methemoglobinemia (a rare blood disorder, more common with overdose)
• Dermatitis or skin irritation at application site (ointments/patches)

Drug interaction

Nitroglycerin has significant interactions with several drug classes:

• Phosphodiesterase-5 Inhibitors (e.g., Sildenafil, Tadalafil, Vardenafil): CONTRAINDICATED. Concomitant use can cause severe, potentially fatal hypotension.
• Other Vasodilators and Antihypertensives (e.g., beta-blockers, calcium channel blockers, ACE inhibitors, ARBs, alpha-blockers, other nitrates): Additive hypotensive effects. Blood pressure must be monitored closely.
• Alcohol: Potentiates the vasodilatory and hypotensive effects of nitroglycerin.
• Dihydroergotamine: May decrease the vasoconstrictive effect of dihydroergotamine.
• Heparin: Nitroglycerin may partially counteract the anticoagulant effect of heparin.

Missed dose

• For scheduled/prophylactic doses (ointment, 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 regular schedule. Do not double the dose.
• For acute/as-needed doses (sublingual, spray): This does not apply, as the medication is only taken during an angina attack. There is no schedule to miss.

Overdose

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

• Signs and Symptoms: Profound hypotension with violent throbbing headache, dizziness, visual disturbances, flushing, cold and clammy skin, nausea/vomiting, syncope, air hunger, dyspnea, slow pulse (bradycardia), heart palpitations, paralysis, coma, seizures, and cyanosis with methemoglobinemia.
• Management: Seek emergency medical attention immediately. Primary treatment involves placing the patient in a recumbent position (Trendelenburg position if necessary) and administering intravenous fluids to support blood pressure. If methemoglobinemia is present (evidenced by chocolate-brown colored blood and cyanosis unresponsive to oxygen), specific antidotes like methylene blue may be administered. Epinephrine is ineffective and potentially harmful for correcting hypotension.

Storage

• Store at room temperature (68°F to 77°F / 20°C to 25°C) away from light, moisture, and heat.
• Sublingual Tablets: EXTREMELY IMPORTANT: Keep tablets in their original glass container with the cotton wool removed. The container must be tightly closed immediately after each use. Tablets are highly volatile and lose potency rapidly if exposed to air, light, or plastic. Do not transfer to pill boxes or other containers.
• Spray: Do not puncture, burn, or expose the canister to high heat.
• Do not store in the bathroom or glove compartment of a car. Keep all medications out of the reach of children and pets.

Disclaimer

This information is for educational 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 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 errors or omissions or for any consequences from the application of this information.

Reviews

• “As a cardiologist with over 20 years of practice, nitroglycerin remains the gold standard for immediate relief of angina. Its rapid onset and predictable effect are unparalleled. Patient education on proper storage and the critical importance of the nitrate-free interval is paramount for long-term efficacy.” – Dr. A. Reynolds, MD, FACC
• “This medication has given me my life back. I keep the spray with me at all times. Knowing I can stop an attack within minutes allows me to garden and play with my grandchildren without constant fear. The headaches were intense at first but have lessened significantly.” – Patient, M, 68
• “The introduction of a transdermal patch regimen, with a strict off-period, has drastically reduced the frequency of my husband’s angina episodes. It requires discipline in application timing, but the improvement in his daily stability has been remarkable.” – Caregiver
• “From a clinical pharmacy perspective, the most critical counseling point is the absolute contraindication with ED medications like Viagra. This interaction can be fatal, and patient understanding is non-negotiable. Furthermore, reinforcing proper storage of sublingual tablets is essential to maintain drug potency.” – Clinical Pharmacist, BScPhm