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Nitrates for Treating Angina

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Nitrates have been a mainstay in the treatment of angina for over 100 years. Nitrates work by dilating both arteries and veins, both in the heart and elsewhere. This general dilation of blood vessels reduces stress on the heart muscle, and thus reduces the amount of oxygen the heart requires. Reducing the amount of oxygen used by the heart allows the heart to function longer without developing ischemia, even when blood flow through the coronary arteries is partially blocked by atherosclerosis. Nitrates can be used acutely to help relieve episodes of angina, and chronically to help prevent angina from occurring.

Sublingal (SL) nitroglycerin (nitroglycerin that is rapidly absorbed from under the tongue) is the oldest form of nitrate therapy. SL nitroglycerin is the quickest way to relieve an episode of angina brought on by exercise or stress, and commonly provides relief within minutes. Also, taking SL nitroglycerin just before engaging in activities that are likely to cause symptoms (such as climbing a hill or walking in the cold) can help in preventing angina. SL nitroglycerin begins dilating blood vessels within two minutes, and its effect can last up to 30 minutes.

Nitroglyerin spray, delivered into the mouth by a metered dose device, works similarly to SL nitroglycerin - it is simply another method of delivering a rapid-acting dose of nitroglycerin.

Nitrates, when administered in pill form or by skin patches, can also be used as chronic therapy to help prevent episodes of angina. The most commonly used pill form of nitrates is isosorbide dinitrate (Isordil, Sorbitrate). Its effect on blood vessels begins within approximately 30 minutes, and lasts for up to six hours. Transdermal nitroglycerin patches, which deliver nitroglycerin through the skin, provide effective nitrate therapy for eight to 14 hours.

The biggest problem with the chronic use of nitrates has been the phenomenon of "tolerance." With nitrate tolerance, chronic exposure to nitrates causes a diminished effect, so that effective dilation of blood vessels is no longer seen, and the anti-anginal effect of the drug disappears. This nitrate tolerance can be prevented by scheduling the dosing of chronic nitrate therapy in such a way as to guarantee daily nitrate-free intervals. So: oral nitrates or nitrate skin patches should only be used for 12 to 16 hours per day, with an eight to 12 hour "nitrate-free" interval. For most patients this means that nitrates are used during waking hours, and not during sleep. In some patients with nocturnal angina, however, the nitrate-free interval may need to be scheduled during waking hours.

Nitrates should not be used in patients with hypertrophic cardiomyopathy (in whom nitrates can cause a dangerous obstruction to blood flow within the heart), or in patients who are taking Viagra (sildenafil) or other similar agents for erectile dysfunction. (Taking nitrates and Viagra together can produce severe hypotension - low blood pressure.)

The most common side effects of nitrates are headache and flushing, though lightheadedness from hypotension can also occur. Patients with a history of migraine headaches often cannot tolerate nitrates.

Read here for more on the noninvasive treatment of angina.

Sources:

Parker, JD, Parker, JO. Nitrate therapy for stable angina pectoris. N Engl J Med 1998; 338:520.

Abrams, J. Hemodynamic effects of nitroglycerin and long-acting nitrates. Am Heart J 1985; 110:216.

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