Nitroglycerin relaxes and widens blood vessels, allowing more blood to flow to the heart while reducing how hard the heart has to work. It’s best known as the small tablet you dissolve under your tongue during chest pain, but it also comes in patches, sprays, and ointments for different conditions. The drug works fast, often within minutes, and has been a cornerstone of heart treatment for over a century.
How Nitroglycerin Works in the Body
Once nitroglycerin enters your body, enzymes inside your cells convert it into nitric oxide, a molecule that signals blood vessel walls to relax. The key conversion happens inside mitochondria (the energy-producing structures in your cells), where an enzyme breaks nitroglycerin down into nitric oxide and related compounds.
That nitric oxide then triggers a chain reaction in the smooth muscle cells lining your blood vessels. It activates a chemical messenger that lowers calcium levels inside those muscle cells. Since calcium is what makes muscles contract, reducing it causes the vessel walls to loosen and widen. The result is vasodilation: your veins expand, less blood returns to the heart at once, and the heart doesn’t have to pump as forcefully. Your arteries also relax, lowering blood pressure and reducing the oxygen demand on your heart muscle.
This is why nitroglycerin relieves angina (chest pain from reduced blood flow to the heart). The heart was starving for oxygen, and nitroglycerin eases the workload while simultaneously opening up the coronary arteries that feed it.
How It’s Used for Chest Pain
Sublingual nitroglycerin, the type placed under your tongue or between your cheek and gum, is the classic form for acute angina. Tablets come in three strengths: 0.3 mg, 0.4 mg, and 0.6 mg. There’s also a spray version that delivers the drug directly onto or under the tongue.
At the first sign of chest pain, you dissolve one tablet under your tongue. You should feel relief within about five minutes. If the pain persists, you can take a second tablet after five minutes, and a third five minutes after that. The critical rule: no more than three doses in 15 minutes. If your pain doesn’t improve or gets worse after the first dose, call 911 immediately. Don’t wait to finish all three tablets before seeking help.
You can also use nitroglycerin preventively. Taking a tablet or using a spray 5 to 10 minutes before physical activity or a stressful situation can ward off an angina episode before it starts.
Other Forms and Uses
Beyond the sublingual tablet, nitroglycerin comes in several other forms designed for longer-lasting or different effects.
Transdermal patches deliver a steady, low dose through the skin over many hours. They’re used to prevent angina rather than treat an acute attack. One important limitation: your body develops tolerance to continuous nitroglycerin surprisingly fast, sometimes within 24 hours of wearing a patch nonstop. To counter this, patches are typically worn for about 12 hours and then removed for a 12-hour drug-free period. Some people experience a rebound effect during that off period, with worsening chest pain or reduced exercise tolerance, so the timing needs to be managed carefully with a doctor.
Nitroglycerin ointment applied rectally treats a completely different condition: chronic anal fissures, which are painful tears in the skin around the anus. The same vasodilating mechanism relaxes the muscles around the anal canal, reducing pressure in the area and allowing the fissure to heal. The ointment is typically applied every 12 hours.
Common Side Effects
The most frequent side effect is headache, and it’s not subtle. Because nitroglycerin dilates blood vessels throughout the body, including in the brain, it can cause significant head pain. In clinical studies using intravenous nitroglycerin, headaches occurred in the majority of participants. The vasodilatory effects in the brain typically peak and resolve within about 45 minutes, so headaches from sublingual tablets tend to be short-lived. Other common side effects include lightheadedness, a drop in blood pressure, rapid heartbeat, and nausea.
The lightheadedness happens because widening veins causes blood to pool in your lower body, temporarily reducing blood flow to your brain. Sitting or lying down when you take nitroglycerin helps prevent this.
The Dangerous Interaction With ED Medications
Nitroglycerin should never be combined with erectile dysfunction medications like sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra). Both drug types lower blood pressure through related pathways, and together they can cause a sudden, severe drop that becomes life-threatening.
Nitroglycerin boosts a chemical messenger that relaxes blood vessels. ED medications work by preventing that same messenger from being broken down. The combination floods the system, causing blood pressure to plummet. The American College of Cardiology recommends waiting at least one to two days after the last dose of an ED medication before taking any form of nitrate. This applies to all nitroglycerin forms, including long-acting nitrate pills and transdermal patches.
Storing Nitroglycerin Properly
Sublingual nitroglycerin tablets are notoriously fragile. The drug evaporates and degrades when exposed to heat, light, moisture, or even the wrong container material. Tablets stored in small, amber, tightly capped glass bottles in a refrigerator maintain their potency for about three to five months if the bottle is opened only about once a week. After five months, unused tablets should be thrown out.
Carrying tablets loose in a pill box is far worse. Tablets stored this way can lose their effectiveness within a single week. Cotton, plastic, or paper stuffed inside the bottle also accelerates degradation, as does opening the bottle frequently. If your nitroglycerin tablet doesn’t produce a slight tingling or burning sensation under your tongue, it may have lost potency and should be replaced. When you’re relying on this drug during a cardiac emergency, a stale tablet is the last thing you need.
Tolerance Over Time
With continuous or frequent use, your body becomes less responsive to nitroglycerin. This is called nitrate tolerance, and it can develop quickly. In studies of transdermal patches, measurable tolerance appeared within 24 hours of continuous wear. The enzyme responsible for converting nitroglycerin to nitric oxide becomes depleted with sustained exposure, reducing the drug’s effectiveness.
This is why long-acting nitroglycerin, whether patches or extended-release pills, requires a daily drug-free window. For sublingual tablets used only during acute chest pain episodes, tolerance is less of a concern because the exposure is brief and intermittent. But for anyone using nitroglycerin regularly, the balance between maintaining protection and preserving the drug’s effectiveness is an ongoing consideration.