| Autor: |
Frishman, William H., Giles, Thomas, Greenberg, Steven, Heiman, Mark, Raffidal, Louise, Soberman, Judith, Laifer, Larry, Nadelmann, Jeremy, Lazar, Eliot, Strom, Joel |
| Zdroj: |
Journal of Clinical Pharmacology; Dec1989, Vol. 29 Issue 12, p1097-1105, 9p |
| Abstrakt: |
The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2. Headache was the most common side effect, and with the 1-hour treatment withdrawal there was no evidence of angina rebound. High-dose continuous nitroglycerin patch therapy is well tolerated in patients, and there is some evidence of antianginal efficacy during the first 24 hours of therapy. However, despite the high plasma nitroglycerin drug levels seen with continued use of high-dose therapy, there is an attenuation of hemodynamic and antianginal effects, suggesting the development of pharmacological tolerance. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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