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Transdermal nitroglycerin patch placed at 7AM then removed and replaced with another at 7PM
37%
94/255
PO regular-release isosorbide dinitrate taken at 8AM, noon, and 5PM
18%
45/255
Transdermal nitroglycerin patch placed at bedtime and removed at 7AM without replacement
15%
37/255
Transdermal nitroglycerin patch placed upon awakening in the morning and removed at 7PM without replacement
13%
32/255
PO extended release isosorbide-5-mononitrate once daily at 8AM
11%
28/255
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This patient's presentation is consistent with nitrate tolerance due to an insufficient nitrate-free interval in his medication dosing schedule. Immediate replacement of a transdermal nitroglycerin patch does not allow a sufficient nitrate-free interval. Nitrate tolerance typically develops after 24 to 48 hours of continuous treatment. The development of tolerance on long-term, prophylactic nitrates is a primary limitation of this therapy; tolerance is best avoided by incorporating a nitrate-free interval of 8-12 hours into the dosing schedule. Rebound angina is noted in some patients during their nitrate-free interval, and concomitant use of an additional anti-anginal therapy is recommended to prevent this rebound effect. This is especially important given the fact that myocardial infarction and sudden death occur most commonly in the early morning hours, a time when many patients on anti-anginal therapy are in the midst of their medication-free interval. Kosmicki discusses the mechanism of nitrate tolerance in the setting of long-acting nitrates used to treat stable angina. Long-term exposure to nitrates can lead to the development of reactive oxygen species (ROS) in vascular smooth muscle cells. ROS then binds nitric oxide (NO), leading to decreased NO activity and therefore the development of nitrate tolerance. Sublingual nitroglycerin therapy can induce cross-tolerance to oral nitrates. Incorrect Answers: Answer 2: Isosorbide dinitrate lasts for a maximum of 6 hours; this dosing schedule allows for a sufficient nitrate-free period overnight while the patient is sleeping. Answer 3: This is a common dosing regimen for patients who experience nocturnal angina; this allows for a prolonged nitrate-free period during the daytime. Answer 4: This is a common dosing regimen for patients who experience angina during activity; this allows for a prolonged nitrate-free period overnight. Answer 5: This allows for a sufficient nitrate free period, and nitrate tolerance would not be expected to develop on this dosing regimen.
2.5
(14)
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