Nitroglycerin – Effects, Uses and Dosage

What is Nitroglycerin?

Nitroglycerin (Latin: Nitroglycerinum), also known as glyceryl trinitrate or GTN, is an organic nitrate and one of the oldest and most effective medications in cardiology. It is primarily used to treat and prevent angina pectoris – episodes of chest pain caused by reduced blood supply to the heart muscle. Nitroglycerin belongs to the class of nitrovasodilators and is included on the World Health Organization (WHO) Model List of Essential Medicines.

Mechanism of Action

Nitroglycerin is enzymatically converted in the body to nitric oxide (NO). Nitric oxide activates the enzyme guanylate cyclase, leading to increased intracellular levels of cGMP (cyclic guanosine monophosphate). This causes relaxation of smooth muscle cells in blood vessel walls, resulting in vasodilation (widening of blood vessels).

• Venous vasodilation: The primary effect – reduces cardiac preload and lowers the oxygen demand of the heart muscle.
• Arterial vasodilation: At higher doses – lowers blood pressure and reduces afterload.
• Coronary vasodilation: Widens coronary arteries and improves blood flow to ischemic areas of the heart.

Indications

Nitroglycerin is used in various clinical situations:

• Acute angina pectoris attacks (emergency relief)
• Prophylaxis of angina episodes before physical exertion
• Acute coronary syndrome and myocardial infarction (as adjunct therapy)
• Acute heart failure and pulmonary edema
• Hypertensive emergency (severely elevated blood pressure)
• Controlled blood pressure reduction during surgical procedures

Dosage Forms and Administration

Nitroglycerin is available in several forms, each suited to different clinical needs:

Sublingual (under the tongue)

The most common form for acute treatment. Tablets or spray are placed under the tongue. Onset of action within 1–3 minutes, duration approximately 20–30 minutes. Typical dose: 0.4 mg spray or 0.3–0.6 mg tablet. If symptoms persist, the dose may be repeated after 5 minutes (maximum 3 doses).

Transdermal Patches

Used for long-term prophylaxis. The patch delivers nitroglycerin continuously through the skin. To prevent nitrate tolerance, a nitrate-free interval of 8–12 hours per day is required.

Intravenous Infusion

Used in intensive care and emergency settings for precise blood pressure control or management of acute heart failure. Allows accurate dose titration.

Extended-Release Capsules and Tablets

Used for oral long-term prophylaxis with delayed drug release.

Side Effects

The most common side effects of nitroglycerin are related to its vasodilatory action:

• Headache (very common, affecting up to 50% of patients)
• Dizziness and orthostatic hypotension (drop in blood pressure upon standing)
• Skin flushing (flush)
• Nausea and vomiting
• Reflex tachycardia (increased heart rate in response to blood pressure drop)
• In case of overdose: severe hypotension, fainting, methemoglobinemia

Contraindications and Important Warnings

Nitroglycerin should not be used, or used only with caution, in the following situations:

• Concurrent use of PDE-5 inhibitors (e.g., sildenafil, tadalafil) – potentially life-threatening drop in blood pressure
• Severe low blood pressure (hypotension, systolic below 90 mmHg)
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Severe aortic valve stenosis or cardiac tamponade
• Elevated intracranial pressure or severe head trauma
• Known hypersensitivity to nitrates

Nitrate Tolerance

With continuous use and no nitrate-free intervals, the body develops nitrate tolerance: the cardiovascular response to the drug diminishes over time. To prevent this, a daily nitrate-free period is recommended during long-term therapy. Sublingual use for acute episodes is largely unaffected by this phenomenon.

References

1. World Health Organization (WHO) – Model List of Essential Medicines, 23rd Edition (2023). Available at: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02
2. Brunton LL, Knollmann BC (eds.) – Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition. McGraw-Hill Education, 2023.
3. Münzel T, Daiber A, Mülsch A – Explaining the phenomenon of nitrate tolerance. Circulation Research, 2005;97(7):618–628. PubMed PMID: 16195486.