Nitrates are a class of cardiovascular medications that relax and widen blood vessels. They’re primarily prescribed to treat angina, the chest pain that occurs when your heart muscle doesn’t get enough blood flow. The most well-known nitrate is nitroglycerin, but several other formulations exist in both fast-acting and long-acting versions.
How Nitrate Drugs Work
All nitrate medications share the same basic mechanism: once inside your body, they release nitric oxide, a molecule that causes the smooth muscle in your blood vessel walls to relax. This widens your arteries and veins, which does two things. It lowers the amount of blood returning to the heart (reducing the heart’s workload), and it improves blood flow through the coronary arteries that feed the heart muscle itself. The result is rapid relief from angina pain.
What makes nitrates unique is that this conversion to nitric oxide happens through an enzyme-driven process specific to vascular tissue. In other words, nitrates are “targeted” to blood vessels, which is why they’re so effective for heart-related chest pain.
Short-Acting Nitrates
Short-acting nitrates are designed for immediate relief during an angina episode or for prevention just before physical activity you know triggers symptoms.
- Nitroglycerin sublingual tablets (Nitrostat): Small tablets placed under the tongue that dissolve within seconds. These are the classic “heart pills” many people associate with angina.
- Nitroglycerin sublingual spray (Nitrolingual): A pump spray applied under the tongue, used the same way as the tablets for rapid symptom relief.
- Nitroglycerin intravenous: Used in hospital settings for acute chest pain or heart emergencies where doctors need precise control over dosing.
These formulations work within one to three minutes and typically last 20 to 30 minutes. Many people with known angina carry sublingual nitroglycerin tablets or spray with them at all times.
Long-Acting Nitrates
Long-acting nitrates are taken on a daily schedule to prevent angina episodes from occurring in the first place rather than treating them once they start.
- Isosorbide mononitrate standard-release tablets (Monoket, Ismo): Taken twice daily, spaced 6 to 8 hours apart, with a gap overnight to prevent tolerance.
- Isosorbide mononitrate extended-release tablets (Imdur): Taken once daily, starting at 30 or 60 mg and sometimes increased to 120 mg. In rare cases, doses up to 240 mg are used.
- Isosorbide dinitrate (Isordil): An older formulation that your body converts into isosorbide mononitrate. Less commonly prescribed today.
- Nitroglycerin patches (Nitro-Dur, Minitran): Transdermal patches worn on the skin that deliver a steady dose over 12 to 14 hours, then removed overnight.
- Nitroglycerin ointment (Nitro-Bid): A topical paste applied to the skin, though this is less commonly used now that patches are available.
The Tolerance Problem
One quirk of nitrate medications is that your body adapts to them quickly if exposure is continuous. This phenomenon, called nitrate tolerance, means the drug gradually stops working as well. To prevent this, all long-acting nitrate regimens include a daily “nitrate-free interval” of at least 12 hours. That’s why isosorbide mononitrate tablets are taken with an asymmetric schedule (morning and afternoon, but not at bedtime), and nitroglycerin patches are removed at night. This daily break gives your blood vessels time to reset their sensitivity to the drug.
Common Side Effects
Because nitrates widen blood vessels throughout the body, not just in the heart, their side effects are predictable. Headaches are the most frequent complaint, and they’re actually a sign the medication is working as intended. For many people, these headaches ease over the first few days of treatment.
Dizziness and lightheadedness are also common, especially when standing up quickly from a sitting or lying position. This happens because the widened blood vessels temporarily lower your blood pressure, and gravity pulls blood away from your brain. Getting up slowly helps. Flushing, or a warm redness in the face and neck, can also occur.
The Critical Interaction With ED Medications
The most important drug interaction to know about is between nitrates and erectile dysfunction medications like sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). Both drug classes widen blood vessels, but they do it through connected pathways. Nitrates boost the production of a signaling molecule that relaxes blood vessels, while PDE5 inhibitors block the enzyme that breaks that same molecule down. Together, the effect multiplies rather than simply adding up, and blood pressure can drop to dangerously low levels.
The timing matters: sildenafil and vardenafil remain active for about 24 hours, while tadalafil stays in the body for up to 36 hours. You cannot safely take any nitrate during those windows. This interaction applies to all nitrate formulations, including sublingual tablets, sprays, patches, and long-acting pills.
Who Should Not Take Nitrates
Beyond the ED medication interaction, nitrates are contraindicated in several specific situations. People with hypertrophic cardiomyopathy, a condition where the heart muscle is abnormally thick, may find that nitrates actually worsen their angina. Nitrates are also contraindicated in constrictive pericarditis and pericardial tamponade, conditions where the sac around the heart is compressed, because the heart in these cases depends on a full volume of returning blood to function, and nitrates reduce that volume.
Patients in circulatory shock or with very low blood pressure should not receive nitrates, since further blood pressure drops could be life-threatening. Severe anemia and increased pressure inside the skull are also contraindications listed by the FDA.
Nitrates vs. Nitrites: A Common Confusion
People sometimes confuse prescription nitrate drugs with alkyl nitrites, commonly known as “poppers.” These are chemically and medically distinct. Prescription nitrates are non-volatile compounds taken as pills, sprays, or patches for heart disease. Alkyl nitrites are volatile liquids inhaled recreationally for a brief rush of euphoria and muscle relaxation. Both release nitric oxide in the body and cause blood vessel dilation, but nitrites produce a short-lived high that prescription nitrates do not, for reasons that remain unclear. Alkyl nitrites are not licensed as medicines and carry their own set of health risks, including dangerous drops in blood pressure and potential eye damage.
Amyl nitrite was actually the original angina treatment, first used in 1867, but it was quickly replaced by nitroglycerin because it was easier to use and lasted longer. A topical nitroglycerin preparation is also used today for a completely different purpose: treating anal fissures, where its ability to relax smooth muscle helps the tissue heal.
Where Nitrates Fit in Heart Treatment
In the most recent 2025 guidelines from the American College of Cardiology and American Heart Association, nitrates remain a standard option for managing chest pain in acute coronary syndromes. They’re effective for symptom relief, though the guidelines note they haven’t been shown to improve long-term outcomes like survival. When chest pain continues despite nitrate therapy, that’s a signal to pursue more aggressive treatment such as opening the blocked artery directly. Nitrates are a tool for comfort and symptom control, not a substitute for addressing the underlying blockage.