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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
Kyle H. Kim ; Connor C. Kerndt ; Ghufran Adnan ; Derek J. Schaller .
Last Update: July 31, 2023 .
Nitroglycerin is a vasodilatory drug used primarily to provide relief from anginal chest pain. It is currently FDA approved for the acute relief of an attack or acute prophylaxis of angina pectoris secondary to coronary artery disease. Off-label, non-FDA-approved uses include treatment for hypertensive urgency/emergency, coronary artery spasm, angina secondary to cocaine use, congestive heart failure (CHF), and chronic anal fissures. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of nitroglycerin, so providers can direct patient therapy successfully in instances where nitroglycerin benefits patient care.
Identify the approved and off-label indications for using nitroglycerin. Summarize the mechanism of action of nitroglycerin. Outline nitroglycerin's adverse event profile.Describe interprofessional team strategies for improving care coordination and communication to properly use nitroglycerin to improve patient outcomes in the varied scenarios where it can be effective.
Nitroglycerin is a vasodilatory drug used primarily to provide relief from anginal chest pain. Nitroglycerin has been FDA approved since 2000 and was first sold as a brand-name agent. It is currently FDA approved for the acute relief of an attack or acute prophylaxis of angina pectoris secondary to coronary artery disease. Off-label, non-FDA-approved uses include treatment for hypertensive urgency/emergency, coronary artery spasm, angina secondary to cocaine use, congestive heart failure (CHF), and chronic anal fissures. Along with hydralazine as a combination therapy, it is also indicated in patients with heart failure with reduced ejection in whom ACE inhibitors are contraindicated. Nitroglycerin is occasionally given to reduce radial spasms during coronary angiography through the radial approach. Nitroglycerin was first used in 1879 as a treatment for angina and since it has been part of management to relieve anginal chest pain.[1]
Although nitroglycerin has a vasodilatory effect in both arteries and veins, the profound desired effects caused by nitroglycerin are primarily due to venodilation.[2] Venodilation causes pooling of blood within the venous system, reducing preload to the heart, which causes a decrease in cardiac work, reducing anginal symptoms secondary to demand ischemia. Arterial vasodilation will still occur and contribute to the relief of anginal symptoms.[3][4] Vasodilation of the coronary arteries will cause increased blood flow to the heart, increasing perfusion, but this effect remains minimal compared to the effects of venodilation.
As with other nitrates used to treat anginal chest pain, nitroglycerin converts to nitric oxide (NO) in the body. NO then activates the enzyme guanylyl cyclase, which converts guanosine triphosphate (GTP) to guanosine 3',5'-monophosphate (cGMP) in vascular smooth muscle and other tissues. cGMP then activates many protein kinase-dependent phosphorylations, which enhances the reuptake of calcium into the sarcoplasmic reticulum, increases extracellular calcium, and opens the calcium-gated potassium channel.[5][6] This ultimately results in the dephosphorylation of myosin light chains within smooth muscle fibers.[7] This activity causes the relaxation of smooth muscle within blood vessels, resulting in the desired vasodilatory effect.
Nitroglycerin is most commonly administered as a tablet that is absorbed sublingually. It is given in hospitals as well as prescribed for outpatient use. Patients may be prescribed nitroglycerin as prophylaxis for anginal chest pain prior to an event that may provoke anginal symptoms. They must be instructed to allow the nitroglycerin to dissolve in their mouth and allow their oral mucosa to absorb the drug. There currently are three doses available: 0.3 mg, 0.4 mg, and 0.6 mg. The dose is repeatable every 5 minutes until the achievement of relief. If anginal pain persists after three doses, prompt medical attention is required. After administration, the onset of vasodilatory effects occurs within 1 to 3 minutes, with a max effect occurring within 5 minutes. Nitroglycerin is primarily eliminated via metabolism in the liver and has a mean half-life of approximately 2 to 3 minutes.[8]
There are intravenous (IV) routes of administration for nitroglycerin used most commonly in emergency rooms and intensive care units (ICU). It is administered as a 5% dextrose in drip and is indicated when sublingual nitroglycerin has failed to provide symptomatic relief or if rapid and continued relief of symptoms is necessary. Intravenous nitroglycerin is frequently used to treat acute coronary syndromes, hypertensive emergency, and acute congestive heart failure (CHF) exacerbations.[9][10] When administered, its effect requires tight vitals monitoring, as discussed below. It should be kept in mind that continuous intravenous infusion of nitrates can lead to the development of tolerance. It is important to switch patients to oral form with intermittent dose and long nitrate-free intervals to avoid tolerance. Sometimes in a catheterization laboratory, nitroglycerin can be given intracoronary as a treatment for no-reflow.[11] Nitroglycerin provides rapid coronary vasodilation when given intracoronary.
Transdermal methods of nitroglycerin administration are also commonly administered in emergency rooms during acute angina attacks. It is a 2% ointment applied directly to the patient's skin and allowed to absorb. It is typically for patients that cannot tolerate the sublingual administration of nitroglycerin or have a previous adverse reaction to the sublingual tablet. Absorption takes about 5 to 10 minutes for full effect.[12][13] The ideal application is on a surface with minimal hair as hair can inhibit absorption, and care is necessary not to apply repeatedly to the same area if multiple doses are required. Repeated application of the ointment to the same area can cause skin irritation and dermatitis. Transdermal patches are also available at varying doses per hour (0.1 mg, 0.2 mg, 0.4 mg, and 0.6 mg), but these are rarely used and reserved for angina prophylaxis only. Similar application precautions as apply to the ointment also apply to the patches.
Nitroglycerin has many adverse effects of significance, most resulting from the vasodilatory effects of the medication.[14][15] These include:
