Nitrate Therapy

Nitrates are a group of medications that are called vasodilators, because they dilate the walls of blood vessels. Nitrates are primarily used to treat angina pectoris, which is pain caused by reduced blood flow to the heart muscle; as well as hypertension, and heart failure. The most commonly used nitrates include nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate.

Okay, let’s focus on nitroglycerin. Nitroglycerin is lipid soluble so it’s easily absorbed through cellular membranes, so it is typically given through rapidly absorbable routes like sublingual or oral spray to treat acute anginal pain or hypertension; or as transdermal patches or topical ointments for long-term prevention. Nitroglycerin can also be administered rectally for the treatment of anal fissures.

Once absorbed into the blood, nitroglycerin is quickly converted into nitric oxide, which diffuses into the smooth muscle cells of both veins and arteries, causing vasodilation. The result of venous vasodilation is peripheral blood pooling, which decreases preload, or the pressure that stretches the heart as it fills with blood from venous return. At the same time, arterial vasodilation lowers the systemic vascular resistance, which will also reduce the afterload, or the pressure that the heart must work against to eject blood during ventricular contraction. Ultimately, by reducing preload and afterload, nitroglycerin reduces the amount of work the heart has to do, eventually decreasing the heart’s oxygen consumption. Nitroglycerin also dilates the coronary arteries, increasing the blood supply to cardiac muscle.

Common side effects of nitroglycerin are related to its vasodilatory effects and include headache, dizziness, flushing, and peripheral edema. Another important side effect is orthostatic hypotension, when blood pressure falls significantly when the patient stands up too quickly. As a result, these patients could experience lightheadedness or syncope due to decreased blood flow to the brain. In addition, patients may experience reflex tachycardia, which is caused by the sympathetic nervous system triggering an increase in heart rate in response to the hypotension caused by nitroglycerin. Now, patients who continuously use nitroglycerin can develop tolerance to these side effects. Unfortunately, patients may also develop tolerance to the therapeutic effects as well, especially with uninterrupted use. So, this can be prevented by avoiding using nitrates for several hours each day.

Nitroglycerin is contraindicated during right ventricular myocardial infarction, hypotension, shock, and cardiac tamponade. It should not be used in patients with severe anemia, cardiomyopathy, or in patients with increased intracranial pressure or cerebral hemorrhage. As far as drug interactions go, nitroglycerin should never be combined with other substances that cause vasodilation, such as alcoholic beverages, as well as medications used to treat erectile dysfunction, including sildenafil, tadalafil, or vardenafil. If taken together, their combined effects may lead to a significant fall in blood pressure, cardiovascular collapse, and even death.