What Are the Potential Risks and Benefits of Nitroglycerin?

Analysis by Dr. Joseph Mercola Fact Checked

what is nitroglycerin used for

Story at-a-glance -

  • Nitroglycerin works by relaxing the arteries, allowing greater blood flow to the heart and reducing the risk of heart attack. However, when used in continuous treatment it may lose effectiveness and increase the risk of greater damage to the heart during a heart attack
  • Nitroglycerine may also induce hypotension (low blood pressure) in those experiencing rapid heart rate
  • Nitroglycerin is a prodrug, metabolized in the body to nitric oxide, which triggers vasodilation; it may also increase vasodilation through regulation of organic nitrates or increasing the activity of histone acetylases
  • Nitroglycerin should be used responsibly to eliminate chest pain; it may be administered once every five minutes, but if no relief is experienced after three doses, seek immediate medical attention
  • Blocked arteries are a symptom of a greater systemic disease affected by smoking, obesity, diabetes, imbalanced cholesterol levels and high levels of iron

Cardiovascular disease is the leading cause of death in the U.S. and was responsible for 840,768 deaths in 2016.1 According to the American College of Cardiology,2 these numbers decreased by 18.6% between 2006 and 2016. However, the annual financial cost continues to be high, estimated at $351.2 billion in 2014-2015.

The World Health Organization3 estimates 17.9 million people die every year from cardiovascular disease and it is responsible for 31% of all deaths worldwide. Of these deaths, 85% are due to heart attacks and stroke.

The American Heart Association4 reports health behaviors affecting heart disease include tobacco use, physical inactivity, poor nutrition and excess weight. Other risk factors include high blood cholesterol, high blood pressure, metabolic syndrome and kidney disease.

Nitroglycerin is a medication prescribed for sudden chest pain, in the hope of alleviating a heart attack. Before discussing the risks and benefits of the medication, it's helpful to understand why it's prescribed and how it works.

How the Heart Works

Your heart is a muscular organ at the center of your circulatory system, which consists of a network of blood vessels carrying blood, nutrients and oxygen around your body5 This hard-working muscle beats 100,000 times each day, 35 million times every year and delivers 6 quarts of blood every minute throughout your body.6

In different terms, the heart pumps 2,000 gallons of blood every day or enough to fill more than three supertankers in your lifetime. Your heart is located under your rib cage toward the center of your chest and the size will vary depending upon your age and the condition of your heart. Normally an adult heart is the size of an average clenched adult fist.7

Your heart is divided into four chambers, two stacked on top of two more. There is a partition wall between the right and left side known as the septum. Each side is divided into an upper and lower chamber. The upper chamber on both sides is known as the atrium and the lower chamber is referred to as the ventricle.8

The right side of the heart, which includes the right atrium and right ventricle, pumps blood to the lungs, where the blood picks up oxygen and is then returned to the left side of the heart. The blood enters the left atrium, flows into the left ventricle and is then pumped out to the rest of the body.

To accomplish this work consistently, your heart muscle also requires blood, nutrients and oxygen, which are delivered through the coronary arteries. There are two main coronary arteries feeding the left and right side of the heart, which divide into two more arteries and continue to divide in order to feed the heart muscle.9

If you suffer from coronary artery disease, it may have serious implications to the delivery of oxygen and nutrients to the heart muscle. When the heart muscle loses oxygen supply while working it triggers pain, called angina.

If left unchecked it may lead to a heart attack and possibly death. The most common form of coronary artery disease is atherosclerosis, a buildup of plaque on the inner lining of the artery reducing the size of the area in the artery blood may move, essentially blocking blood flow.10

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Nitroglycerin Alleviates Angina by Relaxing Your Arteries

Nitroglycerin is the oldest and most commonly used short-acting agent to treat angina (chest pain). It may be prescribed to treat episodes of chest pain when you suffer coronary artery disease, or narrowing of the blood vessels supplying blood to the heart.11

In some cases, individuals may use nitroglycerin before undertaking activities they believe may trigger an episode of angina, in order to prevent it from occurring and potentially avert a heart attack.12

Nitroglycerin falls under a class of medication called vasodilators as they work by relaxing the blood vessels, reducing the workload on the heart, reducing the oxygen demand, and opening the coronary arteries to allow more oxygen delivery to the heart. Nitroglycerin was discovered more than 150 years ago and belongs to a group of drugs known as nitrates.13

Organic nitrates, such as nitroglycerin, may be rapidly absorbed into the body. The compound is a prodrug metabolized to produce an active metabolite, nitric oxide.14 Nitric oxide then triggers vasodilation through an effect on the vascular smooth muscle cells and impairs platelet activation.

Nitroglycerin may also trigger vasodilation by other indirect mechanisms, such as the regulation of organic nitrate-induced smooth muscle cell relaxation or the increase of the activity of histone acetylases.15

Life-Saving Drug Also Has Some Risk

As you might imagine, the release of nitric oxide in the body is not limited to the coronary arteries. Nitroglycerin is the first line treatment for angina or acute myocardial infarction as vasodilation reduces ischemic damage and increases blood flow to the myocardium.

However, as some use nitroglycerin preventatively, continuous delivery may result in an increased tolerance, which then limits the usefulness of the drug. Tolerance is due in part to inactivation of an enzyme — aldehyde dehydrogenase 2 (ALDH2) — responsible for converting nitroglycerin to nitric oxide.16

Additionally, sustained treatment may affect the myocardial cells’ ability to remain viable following ischemia and therefore result in a larger infarct size during a myocardial infarction, or heart attack. Scientists have found administration of alda-1, an activator of ALDH2, along with nitroglycerin improved metabolism and prevented induced cardiac dysfunction following infarction in an animal study.17

Although nitroglycerin is widely used, the American Heart Association finds tachycardia (rapid heart rate) is a contraindication for administration. Research published in Prehospital Emergency Care18 sought to understand whether nitroglycerin administered for chest pain was a predictor of low blood pressure (hypotension) in those suffering tachycardia, as there has been limited evidence.

They used a retrospective cohort study of patient care reports by Basic Life Support (BLS) providers in a Canadian EMS system over two years. Data showed patients experiencing hypotension before hospitalization while being treated by BLS providers was infrequent.

However, while the risk was low, those patients with tachycardia treated with nitroglycerin had a significant increase in the relative risk of hypotension. It occurred most frequently in those with lower blood pressure before nitroglycerin administration, which the researchers suggest may be included in guidelines for future use.19

Use Nitroglycerin Responsibly

Short-acting nitroglycerin may complement other antianginal therapy in those suffering refractory or recurrent angina, with or without myocardial revascularization. Researchers have found20 administration prophylactically increases walking time during treadmill testing and suppresses or delays ST-segment depression.

This increase in exercise tolerance improves quality of life. When someone experiences intense chest pain, it is crucial to resolve the symptom as quickly as possible. While nitroglycerin does not cure atherosclerosis or other coronary artery disease, it will restore oxygen to the myocardium and reduce the potential for a myocardial infarction and heart cell death.21

There are several formulations of nitroglycerin available in fast-acting forms.22 An aerosol spray or pump spray is a device used to spray fluid under the tongue as an individual experiences angina. Care should be taken the individual does not inhale the spray.

A sublingual packet contains 400 micrograms of powder, which should be dissolved under the tongue at the onset of angina. Tablets may be placed under the tongue or between the gum and cheek, and will dissolve and absorb through the tissues of the mouth. Those who have dry mouth may benefit from nitroglycerin spray instead.

None of these formulations should be swallowed or inhaled. Nitroglycerin will absorb quickly through mouth tissue and provide faster relief than being swallowed and absorbed in the gastrointestinal tract. Once administered, avoid any rinsing or spitting for at least five minutes to ensure all the medication is been absorbed.

Nitroglycerin may be taken at five-minute intervals; however, if no relief is experienced after three doses, seek immediate medical attention.23 Nitroglycerin patches provide continuous treatment, usually delivered at 0.8 mg per hour. The patches are used in 12 hour increments. Most use the patch during the day and remove it at night.

Nitroglycerin ointment is also available but should be applied using a dose measuring applicator and not with bare hands as this increases the amount of the medication absorbed. Although primarily used for angina, nitroglycerin also comes as a rectal ointment for the treatment of anal fissures.24 The drug increases blood flow to the area and speeds healing.

Blocked Arteries Are One Symptom of a Diffuse Systemic Disease

It is important to remember when atherosclerosis appears in the coronary arteries, it's likely also building in other areas of the body. Blockage in the coronary arteries is just one manifestation of a larger and more diffuse systemic disease process.

According to the American Heart Association,25 coronary heart disease develops as plaque blocks the coronary arteries and triggers ischemia. Traditional risk factors include high blood pressure, family history, diabetes and smoking. Being postmenopausal (for women) and obese may also be risk factors.

The risk factors for cardiovascular disease, affecting your coronary arteries, peripheral arteries and risk of stroke and heart attack, are the same.26 While many consider high cholesterol a culprit in cardiovascular disease, I believe the issue is not as simple as looking at one number in your cholesterol panel.

Instead, it is important to remember cholesterol is necessary for the production of hormones,27 vitamin D28 and the manufacture of cell membranes;29 75% of the cholesterol found in your body is made by your liver and 25% of it is found in your brain.30

Better indicators of heart disease are your high-density lipoprotein (HDL)-to-cholesterol ratio and your triglyceride-to-HDL ratio. To determine your HDL to cholesterol ratio, divide your HDL level by your total cholesterol. Ideally, the percentage should be 24% and above. Levels registering 10% and below indicate a significant heart disease risk.

Your triglyceride-to-HDL ratio is achieved by dividing your triglycerides by your HDL level and should ideally measure below 2. Additional factors that have a great influence on your cardiovascular health are your iron level, insulin resistance and chronic inflammation. High iron and insulin resistance both trigger chronic inflammatory processes in your body.

An excess amount of iron causes damage to mitochondria when the iron reacts with hydrogen peroxide, a normal part of energy production, forming hydroxyl free radicals. Elevated iron is also linked to dysfunctional glucose metabolism,31 raising your risk of diabetes at a magnitude similar to obesity.32

High iron levels raise your risk of metabolic syndrome,33 a condition associated with an increased risk of high blood pressure and heart disease.34 In other words, a high iron level increases your risk of mitochondrial dysfunction, obesity, diabetes and high blood pressure, all of which are linked to cardiovascular disease and coronary artery disease.

Unfortunately, high iron is a vastly overlooked factor in heart disease, which is why I recommend keeping an eye on your iron level by getting it measured annually. To learn more, see “Top 4 Reasons to Check Your Iron Level, Not Your Cholesterol.”