Tolerance to isosorbide dinitrate: rate of development and reversal.

Abstract

The present investigation was designed to determine the rate of development of tolerance during initiation of therapy with oral ISDN and the rate of tolerance reversal after withdrawal of this drug. MethodsStudy population. Ten patients, nine men and one woman, ranging in age from 37 to 77 years (mean 56), with stable, exercise-induced angina pectoris were studied. Patients who had had previous exposure to ISDN or other oral or cutaneous nitrate preparations were not included. These patients had been taking nitroglycerin, but this was not used in the 24 hr before study and was not required in any patient during this period of investigation. Other exclusion characteristics included the presence of cardiomegaly, cardiac failure, cerebral vascular disease, hepatic disease, renal dysfunction, or the administration of fl-blocking agents or vasodilators. Patients were also excluded if they had a history of severe headaches or symptoms of postural hypotension after nitroglycerin administration.Study design Day 1. After an overnight fast, control measurements were made of heart rate and blood pressure with patients in the supine and standing positions, and a 5 ml sample of venous CIRCULATION Downloaded from http://ahajournals.org by on

Isosorbide-5-Mononitrate and Atenolol in the Treatment of Stable Exertional Angina

“…Contradictory results have been reported on the development of tolerance to long term treatment with nitrates [4,10,11]. No signs of tolerance appeared in our study, although myocardial ischemia, indicated by ST-D, was higher in the 6th week of medica tion (12 h after administration of IS-5-MN, respectively 24 h after AT) than in the 2nd and the 4th weeks with monotherapy or combination therapy.…”

Development of tolerance to nifedipine in patients with stable angina pectoris.

“…However, we have found distinctions in the development of tolerance to nifedipine and to nitrates. It is well known that tolerance to nitrates rapidly disappears after their withdrawal (Parker et al, 1983). In the case of nifedipine we did not find complete restoration of the effect even 8-10 days after stopping sustained administration of nifedipine.…”

Design and Gamma-Scintigraphic Evaluation of a Floating and Pulsatile Drug Delivery System Based on an Impermeable Cylinder

“…proteins and peptides 3) ; (iii) for time programmed administration of hormones and many drugs such as isosorbide dinitrate, respectively to avoid suppression of normal secretion of hormones in body that can be hampered by constant release of hormone from administered dosage form and development of resistance [4][5][6][7][8][9] ; (iv) avoiding pharmacokinetic drug-drug interactions between concomitantly administered drugs. …”

“…1) Such novel drug delivery has been attempted for: (i) chronopharmacotherapy of diseases which show circadian rhythms in their pathophysiology 2) ; (ii) avoiding degradation of active ingredients in upper GI tract, e.g. proteins and peptides 3) ; (iii) for time programmed administration of hormones and many drugs such as isosorbide dinitrate, respectively to avoid suppression of normal secretion of hormones in body that can be hampered by constant release of hormone from administered dosage form and development of resistance [4][5][6][7][8][9] ; (iv) avoiding pharmacokinetic drug-drug interactions between concomitantly administered drugs. 10) Verapamil hydrochloride (Ver) was chosen as model drug, for it is a potent calcium-channel blocker and has been effective for preventing the time-related occurrence of ischemic.…”