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Effect of Intervals between Doses on the Development of Tolerance to Isosorbide Dinitrate

Parker, John O ; Farrell, Bernice ; Lahey, Karen A ; Moe, Gordon

The New England journal of medicine, 1987-06, Vol.316 (23), p.1440-1444 [Periódico revisado por pares]

Boston, MA: Massachusetts Medical Society

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  • Título:
    Effect of Intervals between Doses on the Development of Tolerance to Isosorbide Dinitrate
  • Autor: Parker, John O ; Farrell, Bernice ; Lahey, Karen A ; Moe, Gordon
  • Assuntos: Adult ; Aged ; Angina pectoris ; Angina Pectoris - drug therapy ; Antianginal agents. Coronary vasodilator agents ; Biological and medical sciences ; Cardiovascular disease ; Cardiovascular system ; Drug dosages ; Drug Tolerance ; Electrocardiography ; Exercise Test ; Fitness equipment ; Heart attacks ; Hemodynamics - drug effects ; Humans ; Isosorbide Dinitrate - administration & dosage ; Isosorbide Dinitrate - therapeutic use ; Male ; Medical sciences ; Middle Aged ; Nitrates ; Patients ; Pharmacology. Drug treatments
  • É parte de: The New England journal of medicine, 1987-06, Vol.316 (23), p.1440-1444
  • Notas: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-1
    ObjectType-News-3
    content type line 23
  • Descrição: We studied the development of tolerance to isosorbide dinitrate in 12 patients with chronic stable angina pectoris. The effect of 30 mg of isosorbide dinitrate on treadmill exercise performance was assessed before and at one, three, and five hours after a single dose. As compared with placebo, the drug increased treadmill walking time until the onset of angina and until the development of moderate angina over the five-hour observation period (P<0.05). The patients then received 30 mg of isosorbide dinitrate twice, three times, and four times daily for a period of one week, and exercise performance was assessed before and at one, three, and five hours after the final morning dose. During sustained treatment two and three times daily, treadmill walking time was longer throughout the five-hour testing period than during the placebo phase (P<0.05). In contrast, during treatment four times daily, treadmill walking time was prolonged at one hour (P<0.05) but not at three and five hours after the last dose. We conclude that tolerance to the clinical effects of isosorbide dinitrate develops with a sustained dosage of 30 mg four times daily, but not when the drug is given two or three times daily. (N Engl J Med 1987; 316: 1440–4.) THE organic nitrates continue to be the most frequently used agents in the care of patients with angina pectoris. For the treatment of episodes of angina, sublingual nitroglycerin is usually employed, but for angina prophylaxis, oral isosorbide dinitrate is the most commonly used nitrate. Isosorbide dinitrate has been shown to be rapidly absorbed after oral administration, and the drug has important hemodynamic and antianginal effects. A single dose of isosorbide dinitrate reduces systolic blood pressure and increases treadmill walking time for several hours, 1 , 2 but during therapy four times a day for a period of only one week, both the hemodynamic . . .
  • Editor: Boston, MA: Massachusetts Medical Society
  • Idioma: Inglês
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