Biomedical subjects

G Reiniger

Publications and source records attributed to G Reiniger.

24 records · Page 2Linked to original sources

PubMed1985

[High-dose transdermal nitroglycerin therapy: loss of effect within 24 hours?].

Within a relatively short period of time, nitroglycerin patches have come into widespread use for treatment of coronary artery disease in the absence of sufficient clinical data in support of their efficacy. Presently, there is still considerable controversy regarding the extent and duration of action as well as the dosage requirements. Accordingly, a study was carried out in six patients with angiographically-documented coronary artery disease, stable exercise-induced angina pectoris and reproducible ST-segment depression to analyze the effects of nitroglycerin patches, formulated to deliver 5 mg, 10 mg, 20 mg as well as 30 mg per 24 hours, respectively, on the extent of ST-segment depression. In a further study, the extent and duration of antianginal and anti-ischemic effects of nitroglycerin patches delivering 30 mg/24 hours were investigated in ten patients according to a randomized, double-blind, crossover placebo-controlled protocol. In seven of these patients, testing was again performed at 2.5 hours after repeated application (second application at 24 hours) (Figure 1). Nitroglycerin patches delivering 5 mg, 10 mg, 20 mg as well as 30 mg/24 hours, respectively, led to significant reductions in ST-segment depression at 2.5 hours of 59% (range 25 to 100%; p less than 0.025), 63% (0 to 100%, p less than 0.01), 77% (50 to 100%, p less than 0.001) as well as 82% (50 to 100%, p less than 0.005) as compared with control values (Figure 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1985

[Long-term therapy of stress angina pectoris by a single daily administration of 120 mg isosorbide dinitrate in retard form. Comparison of monotherapy and combination therapy with atenolol and nifedipine].

This study was undertaken to determine whether an effective antianginal treatment without tolerance development can be carried out with intermittent nitrate administration on a regimen with a single daily dose of 120 mg isosorbide dinitrate (ISDN) in sustained-release form (SR), as well as whether the concomitant administration of 100 mg atenolol or 100 mg atenolol and 20 mg nifedipine renders an additive antiischemic effect. In two independently performed investigations, the duration of action of a single dose of 120 mg ISDN SR was assessed after its initial administration in addition to the anti-ischemic effect during long-term treatment, each according to a randomized, double-blind, crossover, placebo-controlled protocol in a total of 15 patients with angiographically-documented coronary artery disease, stable angina pectoris and reproducible ST-segment depression during exercise. The test phases of four weeks each were separated by one week placebo phases. After completion of the study, for a further eight weeks, 120 mg ISDN SR was given together with 100 mg atenolol in the morning. Exercise testing was carried out after four weeks of treatment in a control period before and at two hours after administration of 120 mg ISDN SR with 100 mg atenolol as well as after another four weeks in a control period before and after concomitant administration of 120 mg ISDN SR, 100 mg atenolol and 20 mg nifedipine in sustained release form.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1985

[Therapy of coronary heart disease with nitroglycerin patches. Behavior of anti-ischemic effectiveness in continuous administration and following patch free interval].

Subsequent to the finding of a rapidly attenuated anti-ischemic effect on use of high-dose nitroglycerin patch treatment in patients with coronary artery disease as well as contradictory results obtained with low-dose patch treatment, there are still no reliable guidelines for the use of transdermal nitroglycerin patch therapy. Accordingly, this study was carried out in ten patients with angiographically-documented coronary artery disease, stable exercise-induced angina pectoris and reproducible ST-segment depression, to assess the extent and duration of antianginal and anti-ischemic action of nitroglycerin patch treatment at an intermediate dosage of 15 mg/24 hours after the initial application, after renewed patch application on the second day and after patch application on the third day which had been preceded by a ten-hour patch-free interval in the night. At 2.5 hours after initial application of the nitroglycerin patch there was a 64% reduction in exercise-induced ST-segment depression from 2.6 mm +/- 0.21 (SEM) to 0.93 mm +/- 0.29 (p less than 0.001) (Figures 1 and 2). The exercise capacity to onset of 1 mm ST-segment depression was increased 132% from 191 watt X min +/- 15 (SEM) to 442 watt X min +/- 47 (p less than 0.001), (Figure 3). Eight hours after the initial patch application, exercise-induced ST-segment depression was reduced 37% from 2.6 mm +/- 0.19 to 1.65 mm +/- 0.18 (p less than 0.01); the exercise capacity to onset of 1 mm ST-segment depression was increased 39% from 178 watt X min +/- 18 to 245 watt X min +/- 19 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1984

[Prevention of the development of tolerance to isosorbide dinitrate in interval therapy].

A number of carefully controlled studies in recent years have unequivocally documented evidence of tolerance development with respect to anti-ischemic effects during longterm treatment with nitrates [1, 3, 4, 5, 7, 8]. To determine to what extent tolerance development can be circumvented through an interval regimen, a study was performed in ten patients with stable angina pectoris and reproducible ST-segment depression according to a randomized, double-blind, cross-over, placebo-controlled protocol. Analysis of the anti-ischemic effect of 20 mg ISDN was carried out after acute administration and during chronic treatment on an interval regimen with the administration of 20 mg ISDN in the morning (at 8 a.m.) and at midday (1 p.m.) (Figure 1). On acute administration, 20 mg ISDN led to a reduction in ST-segment depression from 2.15 to 0.40 mm (p less than 0.01) and during longterm treatment from 2.25 to 0.40 mm (p less than 0.01) (Figure 2, Table 1). After acute administration the plasma concentration of ISDN was 9 ng/ml, 2-ISMN 34 ng/ml and 5-ISMN 149 ng/ml (Figure 5, Table 2). Of the control values during longterm treatment, a detectable level was found only for 5-ISMN with a concentration of 36 ng/ml while that of both 2-ISMN and ISDN was 0 ng/ml. On renewed administration, there was an increase of ISDN to 9 ng/ml, 2-ISMN to 37 ng/ml and 5-ISMN to 208 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1984

[Development of tolerance with regard to the anti-ischemic effect of isosorbide dinitrate in regular multiple daily administration].

In previous studies it had been shown that during longterm treatment of coronary artery disease with isosorbide dinitrate (ISDN) in sustained-release form, there was no reduction in exercise-induced ST-segment depression, no decrease in the rate of anginal attacks or nitrate consumption and no changes in blood pressure or heart rate [1, 4]. To determine to what extent tolerance development is a fundamental property of longterm administration of ISDN, this study, carried out according to a randomized, double-blind, cross-over, placebo-controlled protocol (Figure 1), was undertaken. The anti-ischemic effects of 40 mg ISDN were analyzed after acute administration and during longterm treatment with 40 mg four times daily in eleven patients with stable angina pectoris and reproducible ST-segment depression. Additionally, the influence of this therapy on the anti-ischemic effects of 0.8 mg sublingually-administered nitroglycerin (GTN) was assessed in ten of the eleven patients. On acute administration, 40 mg ISDN led to a reduction in ST-segment depression at one hour from 2.05 to 0.18 mm (p less than 0.01), and at six hours from 2.35 to 1.20 mm (p less than 0.01) (Figure 2, Table 1). During chronic treatment, statistically significant changes were no longer detectable. In eight of the eleven patients there was a complete loss of effects; in the remaining three, a marked attenuation was observed (Figure 3). Acute administration of 40 mg ISDN resulted in plasma concentrations of 221 ng/ml 5-ISMN, 53 ng/ml 2-ISMN and 23 ng/ml ISDN (Figure 6, Table 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1983

Tolerance development during isosorbide dinitrate treatment: can it be circumvented?

Based on studies carried out according to randomized, double-blind, crossover, placebo-controlled protocols, analysis was performed to assess the antiischemic effects of (a) 40 mg ISDN, both after acute administration and during long-term treatment with four doses daily, (b) treatment with 20 mg ISDN twice daily (at 8 a.m. and 1 p.m.), and (c) 0.8 mg sublingually administered NTG during treatment with 40 mg ISDN four times daily. After acute administration of 40 mg ISDN there was a reduction in ST-segment depression from 2.05 to 0.18 mm (p less than 0.01). During chronic treatment, statistically-significant changes were no longer detectable. Sublingual administration of 0.8 mg NTG led to a reduction of ST-segment depression during the acute phase of ISDN from 1.20 to 0.15 mm (-87%; p less than 0.01) and during chronic treatment from 1.90 to 0.90 mm (-53%; p less than 0.01). Accordingly, as compared with changes induced in the acute and placebo phases, the effectiveness of NTG during chronic ISDN treatment was diminished. After acute administration of 20 mg ISDN, ST-segment depression was reduced from 2.15 to 0.40 mm (p less than 0.01) and to a comparable degree during long-term twice-daily treatment, from 2.25 to 0.40 mm (p less than 0.01). There was a significant reduction in the rate of anginal attacks and nitrate consumption. Thus, with respect to the anti-ischemic effectiveness of ISDN, tolerance development is incurred during repeated administration. Concomitantly, the effectiveness of NTG is not essentially negated, but rather diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗