Topical nitroglycerin is a nitrate medication applied directly to the skin. Its primary function within the body is to cause vasodilation, which is the widening of blood vessels. This action is achieved by relaxing the smooth muscle found in the walls of the veins and arteries. The medication is delivered in forms like ointments or transdermal patches, allowing for steady absorption through the skin into the bloodstream.
The Mechanism of Vasodilation
Nitroglycerin functions as a “prodrug,” meaning it must be converted into an active molecule to have its therapeutic effect. Once absorbed, the compound is metabolized by enzymes inside smooth muscle cells to release nitric oxide (NO). This colorless gas is a potent natural signaling molecule that plays a central role in regulating blood flow.
Nitric oxide activates the enzyme guanylate cyclase, which increases the concentration of cyclic guanosine monophosphate (cGMP). Elevated cGMP levels signal the smooth muscle cells lining the blood vessels to relax. This relaxation causes the vessels to dilate, which reduces pressure and increases blood flow throughout the circulatory system.
The primary effect of nitroglycerin is venodilation—the widening of veins—which decreases the amount of blood returning to the heart. This reduction in venous return, called preload, lowers the overall workload on the heart muscle. By decreasing the heart’s oxygen demand, the drug helps prevent the symptoms associated with reduced blood flow to the heart.
Distinct Applications and Administration Methods
Topical nitroglycerin is prescribed for two distinct medical conditions, each requiring a different concentration and application method. The first use is to prevent chest pain, known as angina pectoris, which is caused by coronary artery disease. For this purpose, the drug is formulated in a lower concentration ointment or a transdermal patch designed for systemic absorption.
The medication is not used to stop an acute angina attack because its absorption through the skin is not fast enough to provide immediate relief. Instead, it is used for prevention, with an application site typically on a clean, hairless area of the chest, back, upper arm, or thigh. To ensure a consistent effect and prevent skin irritation, patients are often instructed to rotate the application site daily. The dose is carefully measured using a paper applicator before being spread thinly on the skin and covered.
The second primary use is treating pain associated with chronic anal fissures—small tears in the lining of the anus. This application uses a much lower concentration of nitroglycerin, typically a 0.4% ointment, applied directly to the affected area. The local application of the nitrate causes the internal anal sphincter muscle to relax, decreasing the high pressure that characterizes the condition.
Relaxing the sphincter and reducing pressure allows blood vessels to open up, increasing circulation to the tear. This increased blood flow promotes the healing of the anal fissure, which is often hindered by muscle spasm. The small dose is applied with a covered finger, such as with a finger cot or plastic wrap, just inside the anal canal, usually twice a day.
Managing Common Side Effects
The most frequent side effect of topical nitroglycerin is a headache, which can be severe and throbbing. This pain is a direct consequence of the drug’s mechanism of action, as the vasodilation extends to the blood vessels within the brain. This headache is sometimes seen as a confirmation that the medication is working, and it may diminish in intensity over several weeks as the body adjusts to the therapy.
Another common side effect is a drop in blood pressure (hypotension), which can lead to dizziness or lightheadedness, particularly when standing up quickly. This orthostatic hypotension occurs because widening the veins causes blood to pool, reducing blood pressure when changing positions. Patients are advised to rise slowly from sitting or lying down to mitigate this effect.
With long-term use, the body can develop tolerance, meaning the drug’s effectiveness diminishes over time. To prevent this, a “nitrate-free interval” is required, typically a period of 10 to 12 hours each day, often overnight, when the nitroglycerin patch or ointment is removed. This break allows the body’s vascular system to regain its sensitivity to the nitrate. Headaches can often be managed with over-the-counter pain relievers, such as acetaminophen, after consulting a healthcare provider.
Critical Safety Warnings and Interactions
Topical nitroglycerin interacts significantly with Phosphodiesterase Type 5 (PDE5) inhibitors. These drugs, which include sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), are commonly used to treat erectile dysfunction. Combining nitroglycerin with a PDE5 inhibitor is strictly prohibited due to the risk of a severe drop in blood pressure.
This severe interaction occurs because both drug types increase the effects of the nitric oxide pathway within blood vessels. Nitroglycerin directly provides nitric oxide, and PDE5 inhibitors prevent the breakdown of the cGMP molecule that causes vasodilation. The combination creates a synergistic effect, leading to excessive blood vessel widening and profound hypotension, which can cause cardiovascular collapse.
Patients must wait a specific period after taking a PDE5 inhibitor before using any form of nitrate, including topical nitroglycerin; the required waiting time depends on the specific inhibitor used. Caution is also required for patients with pre-existing conditions like severe anemia, as the drug can impair the blood’s oxygen-carrying capacity. Additionally, those with increased pressure in the brain or specific heart conditions, such as hypertrophic cardiomyopathy, must use the medication with extreme care.