Nitrates are medications that have been used in the treatment of heart conditions for more than 100 years. They are commonly used in the prevention and relief of a type of chest pain, pressure or discomfort called angina. Angina occurs when the heart muscle isn't receiving enough oxygen, usually as a result of coronary artery disease. Nitrates may also be prescribed during a heart attack, in the management of heart failure, or after a catheter-based procedure such as angioplasty and/or stenting. One of the main ways nitrates work is by dilating blood vessels, thus increasing the amount of blood that can flow through the vessel.
There are special precautions that must be taken when storing and using nitrates, and people must follow all of their physician’s orders carefully. People using nitrates for a long period of time are urged not to stop taking them abruptly because this action could cause withdrawal symptoms. Pregnant women are generally advised to avoid taking nitrates.
About nitrates
Nitrates are medications that have been used in the treatment of heart conditions for more than 100 years. They are commonly prescribed to prevent and relieve angina – a type of chest pain, pressure or discomfort that is the main symptom of coronary artery disease. Nitrates prevent and relieve angina by addressing its cause: a lack of oxygen-rich blood to the heart (cardiac ischemia).
Nitrates are the most commonly prescribed vasodilators, or medications that widen the blood vessels. They work by converting into nitric oxide inside the body. Nitric oxide relaxes smooth muscles, most notably the muscles of the heart and blood vessels. As a result, stress on the wall of arteries is reduced, which reduces the heart's need for blood while increasing the flow of blood to the heart. However, depending on the dose, nitrates may not reduce blood pressure because they operate through a different mechanism. At higher doses, however, blood pressure may drop.
Nitrates can be taken in many forms, including:
Intravenous injections, the fastest strategy for relieving angina.
Oral sprays or tablets that dissolve under the tongue (sublingual), dissolve on the side of the mouth or are chewable. These are designed to relieve an angina attack as it is happening. In the past, patients may have been advised that all nitrates in these forms will produce a tingling or burning sensation in the mouth indicating that the drug is active. This is no longer true for most nitrates, and the absence of tingling does not mean that the drug is not working. Patients should wait at least five minutes to see if chest pain diminishes before taking a second dose of the medication. No more than a total of three doses at five minutes apart should be taken during a given period of time.
In the past, patients have been advised to take all three doses before contacting emergency medical services if chest pains do not resolve. In 2004, however, the American Heart Association updated its guidelines to recommend contacting emergency help if the chest pain does not resolve within five minutes of the first dose. This recommendation may be changed by individual physicians who are familiar with the particulars of each patient.
Tablets or time-release capsules. Designed for long-term use in the prevention of angina attacks, tablets or time-release capsules require a longer period of time before taking effect than the strategies listed above.
Ointments or skin patches. Designed for long–term use to prevent angina attacks.
Nitrates may also be prescribed in the following situations:
During a heart attack, an event that can result in permanent heart damage or death. It is also known as a myocardial infarction, because part of the heart muscle (myocardium) may die (infarction). A heart attack occurs when one of the coronary arteries becomes severely or totally blocked, usually by a blood clot. The leading cause of coronary artery disease is atherosclerosis, or "hardening of the arteries."
In the management of heart failure, a serious condition in which the heart is not pumping well enough to meet the body’s demand for oxygen. By opening (dilating) the blood vessels, nitrates reduce the pressure in the veins and make it easier for the heart to pump blood. In this situation, nitrates are usually administered intravenously in a hospital setting.
After stenting. Stenting is the procedure by which a small, metal mesh tube (stent) is inserted into an artery, often immediately after an angioplasty, to hold it open. Nitrates may reduce the incidence of myocardial necrosis (tissue death within the heart caused by a lack of oxygen) following this procedure.
In the management of pulmonary hypertension. This condition occurs when the blood pressure in the lungs becomes elevated, often as a result of cardiac disease.
Patients should not take nitrates within 24 hours after they have taken a medication to increase their sexual potency (e.g., Viagra). People should also avoid nitrates if they have been diagnosed with low blood pressure (hypotension). Before using nitrates, patients should inform their physician if they have had allergic or other types of reactions to nitrates or nitrites.
Other medical conditions may affect the use of nitrates. According to the National Institutes of Health, a physician should be informed of any other disorders, especially:
Recent heart attack. Nitrates can worsen problems associated with a heart attack by lowering blood pressure.
Hypertrophic cardiomyopathy. In this condition, nitrates may decrease the heart's effectiveness.
Pericarditis.
Recent stroke or head injury. Nitrates can worsen these conditions by increasing pressure in the brain.
Severe anemia.
Glaucoma.
Kidney or liver disease.
Overactive thyroid gland (hyperthyroidism).
Potential side effects with nitrates
Common side effects of nitrates include:
Headache. Could be severe, but usually fades rapidly. May be caused by an increased blood flow in the blood vessels of the head.
Low blood pressure (hypotension).
Dizziness or lightheadedness, especially when getting up after sitting or lying down.
Drowsiness, weakness or fatigue.
Fainting (syncope).
Flushed face and neck.
Exercise, exposure to heat, prolonged standing and dehydration can intensify the adverse effects of nitrates.
Drug or other interactions with nitrates
Patients should consult their physician before taking any other medication (either prescription or over-the-counter), nutritional supplements or herbal extracts. Of particular concern to patients taking nitrates are:
Heart medications. These include other vasodilators, antihypertensives (drugs that treat high blood pressure) and antiarrhythmics (drugs that treat irregular heart rates). In combination with nitrates, these medications could produce a severe drop in blood pressure (hypotension).
Erectile dysfunction medications (e.g., Viagra). These can increase the effects of nitrates on blood pressure, causing severe low pressure blood or cardiac arrest.
Alcohol. Drinking alcoholic beverages could also produce a severe drop in blood pressure. Patients taking nitrates should abstain from alcohol use.
Grapefruit juice. Grapefruit juice interferes with the liver’s ability to rid the body of some substances. This could lead to a buildup of nitrates to toxic levels in the body. Though the buildup is less likely if the juice is ingested four or more hours prior to the medicine, patients taking nitrates are advised to refrain from drinking grapefruit juice. Patients may also be instructed to avoid eating grapefruit.
Other substances. Using nicotine, marijuana or cocaine will reduce the effectiveness of nitrates.
Finally, a genetic anomaly found in up to 50 percent of people of Asian descent means that this population may not respond to nitrates.
Lifestyle considerations with nitrates
When first taking a nitrate, patients should avoid operating heavy machinery (e.g., driving) until they know how the medication will affect them. Some patients will become temporarily dizzy or lightheaded immediately after taking nitrate medication. To minimize the risk of injury, patients are advised to sit down when taking nitrates. In addition, some patients get severe headaches after each dose of the medication. These headaches usually fade quickly and become less noticeable after they have been on the medication for several weeks.
When nitrates are taken regularly, patients may develop a tolerance for them. Therefore, physicians will prescribe the lowest dose that is still effective. Incorporating an 8- to 12-hour “nitrate-free” period into each day is also recommended for long-term nitrate users. For instance, patients wearing nitrate skin patches could remove the patch in the early evening and replace it in the morning. Additionally, some studies have shown that folic acid therapy or L-arginine therapy may decrease nitrate tolerance. However, these therapies should only be attempted under the guidance of a physician.
Long-term nitrate users who need to stop taking the medication should do so gradually and under the direction of a physician. Abruptly discontinuing use of the medication could cause withdrawal symptoms.
Other precautions with nitrates
Different types of nitrates will require different precautions:
Storage of nitrate tablets that dissolve under the tongue (sublingual tablets) differs from other medications because the potency of this medication is diminished when exposed to air, moisture or warmth. The pills come in a dark brown bottle with a piece of cotton inside. Patients should remove and discard the cotton from the bottle (and not replace it after each use) because it deactivates the nitrates. It is vital that the medication not be transferred to another container because the original brown container protects the medication from sunlight.
Nitrates can deteriorate. When taking tablets or pills, patients should carefully close the bottle after each use to minimize air exposure and frequently replace any pills they carry with them. Patients should avoid carrying the medication close to their skin, which produces heat and makes the medication deteriorate faster. In addition, when taking medications out of the bottle, patients should not place several in the palm of their hand, choose one and then replace others in the bottle. Even this brief contact with the heat of the skin could change the potency of the pills. Instead, it is recommended that the patient pour the pills into the top of the bottle, take one and replace the others. Nitrates should be stored in a cool, dry place. Once opened, nitrate medications will be good for only three to six months.
Extended-release nitrates are more stable and therefore do not lose their potency as quickly. Patients taking time-release tablets or capsules may notice partially dissolved medications in their stools. Physicians should be notified if this occurs because the pills must be completely digested for the medication to be effective.
Patients using nitrates in an oral spray should be careful never to shake the container or inhale the spray. The medication in the spray is intended to be absorbed into the bloodstream through the mouth. Therefore, patients should refrain from swallowing immediately after spraying the medication. When absorbed through the stomach, nitrates will take longer to affect body functions. This is also true for the chewable tablets, which should be chewed for two minutes before swallowing.
Topical ointments (or lotions) should be placed on the skin, but not rubbed or massaged into the skin. Patients should be careful to remove any remaining ointment from the skin before applying a new dose and to always place the ointment over the same area of skin with each application. Patients using skin patches should use the entire patch. Trimming or cutting the patch can expose the active ingredients to air, causing deterioration.
Symptoms of nitrate overdose
The signs and symptoms of overdose can be similar to the medication’s side effects, but are usually more severe. Patients exhibiting any of these symptoms should contact their physicians immediately:
Severe or prolonged headache or feeling of pressure in the head.
Severe dizziness
Unusual drowsiness, weakness or fatigue
Tachycardia (fast or pounding heartbeat)
Fainting (syncope)
Fever
Convulsions or seizures
Blurred vision
Dry mouth
Weak pulse
Shortness of breath, coughing or wheezing
Bluish tint to lips, fingernails or palms (cyanosis)
Pregnancy use issues with nitrates
The effects of nitrates during pregnancy have not been studied. However, large doses of nitrates in pregnant animals have been found to produce adverse effects on the fetus. Use during pregnancy is not recommended.
It is not known whether nitrates pass to nursing babies through breast milk. Patients should consult their physician about taking nitrates when breastfeeding.
Child use issues with nitrates
There is no indication that the risk of side effects from nitrates is different in children than in adults. However, the safety of nitrate use in children has not been scientifically established. Parents are encouraged to discuss the potential risks and benefits with a pediatric cardiologist, before their children begin nitrate treatments.
Elderly use issues with nitrates
Older adults report a higher frequency and intensity of side effects such as dizziness or lightheadedness. Generally, older patients require lower doses of nitrates.
Questions for your doctor regarding nitrates
Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about nitrates:
What condition are nitrates being prescribed for?
Which type of nitrate is best for me?
Is there an estimate of how long I will have to take nitrates?
What is the dosage?
What should I do if I miss a dose?
What are the side effects of nitrates?
What are the alternatives if I have trouble tolerating nitrates?
Are nitrates safe if I have low blood pressure, recent heart attack or stroke, kidney disease, liver disease, glaucoma or another condition?
Are nitrates safe if I am pregnant or nursing?
Would a lower dose be equally effective?
Will these affect other medications I take?
Which dietary supplements and vitamins should I be careful of?
