Biomedical subjects

J Dirschinger

Publications and source records attributed to J Dirschinger.

At least 55 records · Page 3Linked to original sources

PubMed1990

[Nitrates in the treatment of heart failure].

Organic nitrates were the first peripherally-active vasodilators to be used for the treatment of heart failure. Currently, three nitrate derivatives, glycerol trinitrate, isosorbide dinitrate and isosorbide 5-mononitrate as well as the nitrate-like substance molsidomine are employed clinically. For treatment of heart failure, the decisive hemodynamic effect is a meaningful reduction in ventricular filling pressures with maintenance or even a slight increase in cardiac output. The individual response to nitrates is variable. An important indicator for the effect achievable for a certain dose or for the necessary dosage to affect a defined reduction in ventricular filling pressures, is the magnitude of right atrial pressure. It can be assumed that the latter statement is also valid for the nitrate-like substance molsidomine. An inherent problem with any long-term treatment with nitrates is the incurrence of tolerance. This can be expected with any dosing regimen which leads to nitrate cumulation in the plasma or to nearly-constant, high, plasma concentrations as rendered by multiple daily administration of orally-active nitrates or with continuous transdermal or intravenous nitrate administration. The cause of nitrate tolerance is regarded as an insufficient or absent stimulation of guanylate cyclase and, consequently, inadequate generation of cyclic GMP due to availability of thiol substrate. Since the nitrate-like substance molsidomine appears to be able to stimulate guanylate cyclase independent of thiol groups, tolerance development may not be a limiting factor with this agent. Comparable reduction of diastolic pulmonary artery pressure after acute administration and at the end of one week of treatment with 4 mg molsidomine four times daily has been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗

PubMed1990

[Treatment of heart failure with calcium antagonists].

Vasodilators have a well-established role in the treatment of congestive heart failure. By virtue of their vasodilating properties, the calcium channel blockers have been advocated for use in the treatment of heart failure, in particular, in consideration of the fact that the left ventricular dysfunction in 60 to 70% of the patients with this condition is due to ischemic heart disease, the primary disorder for which the calcium channel blockers are intended to treat. The net hemodynamic effect of calcium channel blockade is the result of two opposing actions: negative inotropy and systemic vasodilation with reflex-induced sympathetic stimulation. The balance is dependent on the prevailing cardiovascular status prior to administration of the drug. In the presence of no or only mild-to-moderate left ventricular dysfunction and intact adrenergic reflexes, a small amount of negative inotropy is readily offset by afterload reduction and adrenergic stimulation. In the presence of severe left ventricular dysfunction sufficiently extensive to lead to heart failure, a condition in which homeostatic reflexes are already attenuated, even a slight amount of negative inotropy can lead to unequivocal deterioration of hemodynamics. Of the three conventional calcium channel blockers, verapamil exerts the most marked negative inotropic effects. Even verapamil, however, has been shown to lead to hemodynamic improvement in some patients, at least after acute administration. Apparently, the cut-off point between beneficial and adverse actions lies at an ejection fraction between 30 and 40% and a pulmonary capillary pressure of about 20 mm Hg. In patients beyond these limits, if treated with verapamil, worsening of heart failure is not uncommon.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗

PubMed1989

[Long-term therapy with nitrates. How can continuous effectiveness be achieved?].

Due to rapidly occurring tolerance, "continuous" administration of nitrates can no longer be considered justified. The development of tolerance can be avoided and, thus, the antiischemic effect maintained during long-term treatment only by providing a nitrate-free interval. Dosing regimens with documented effectiveness in long-term controlled studies are available for both isosorbide dinitrate and isosorbide 5-mononitrate as well as for transdermal nitroglycerin systems.

Administration, Cutaneous↗

PubMed1989

Effectiveness of interval nitrate therapy in angina pectoris.

Because of rapid tolerance development, the use of multiple daily doses of oral nitrates or continuous application of transdermal nitrate systems can no longer be considered justified. Only with an interval treatment, which prevents nitrate accumulation in the plasma such that, from low baseline values, renewed administration of the drug results in a marked increase in plasma concentration, is it possible to utilize the antianginal and antiischaemic effects of nitrates for meaningful long-term treatment. For isosorbide dinitrate and isosorbide 5-mononitrate, as well as for transdermal nitroglycerin systems, interval treatment dosing regimens with maintained effectiveness documented in controlled studies have been delineated. To some degree, the principle of interval treatment can be achieved with continuously applied transdermal patches designed for discontinuous release of their content, which yield maintained though somewhat attenuated effects. Recent studies have shown that the tolerance to nitroglycerin, which develops within the first 12h of contact with currently available transdermal patches, can be prevented by gradually increasing the plasma concentration during this period of time. Evidence for clinically relevant rebound phenomena during interval treatment has not been observed.

Administration, Cutaneous↗

PubMed1988

When does nitrate tolerance develop? What dosages and which intervals are necessary to ensure maintained effectiveness?

To address the issues of tolerance development and its circumvention during long-term treatment with nitrates, several controlled studies have been performed. In patients with coronary artery disease, during long-term treatment with isosorbide dinitrate (ISDN) in sustained-release form at dosages of 20 mg t.i.d., 40 mg t.i.d. and 60 mg t.i.d., both the rate of anginal attacks and the ischaemic reaction to exercise were unaffected. After a marked acute anti-ischaemic effect to 40 mg ISDN in nonsustained-release form, during chronic administration of the same dose four times daily, in association with continuously-high nitrate plasma concentrations, similarly, there were no significant effects. On use of nitroglycerin (NTG) transdermal patches delivering 10 mg, 15 mg and 30 mg per 24 hours, respectively, renewed patch application after 24 hours was not met with the same marked response observed after initial application. Clearly attenuated effects could be seen within 8 to 12 hours. These results show that tolerance development is incurred when the incrementation in plasma concentration after a repeated nitrate dose is of relatively limited magnitude with respect to baseline values. The observation of rapid reversibility of nitrate tolerance lead to the concept of interval treatment which on daily use incorporates a sufficiently long period without nitrate administration. On use of a nitrate-free treatment interval employing a regimen of 20 mg ISDN nonsustained-release form twice daily in the morning and at midday, 120 mg ISDN sustained-release form once daily or 50 or 100 mg isosorbide 5-mononitrate once daily, maintained effectiveness has been documented, as it has also been shown for treatment with NTG patches delivering 10 mg per 24 hours on incorporation of a 12-hour patch-free interval. The currently available patch system with discontinuous NTG delivery does not incur a complete loss of action but a considerable attenuation of its effects indicates the need for further refinements. Thus interval treatment guarantees maintenance of nitrate effects, albeit with the limitation that 24-hour therapeutic coverage is not enabled.

Administration, Cutaneous↗

PubMed1988

Restenosis after balloon dilatation of coronary stenosis, multivariate analysis of potential risk factors.

This study was undertaken to analyze change in stenosis caliber up to six months after PTCA with respect to regression or progression as well as to detect factors which possibly influencing the restenosis rate. A computer assisted system with high accuracy was used for two-dimensional quantitation of stenosis. A linear multivariate analysis was applied to quantitative and qualitative angiographic data as well as to clinical findings obtained before, immediately after and six months post-PTCA in 95 consecutive patients in whom 101 stenoses were dilatated. All patients were on a standard medical regimen of aspirin or coumadin and nifedipine. After six months, 56 patients showed a change in minimal stenosis area (mSA) of less than 1 mm2 (no progression), 33 patients showed a decrease in mSA of greater than 1 mm2 which rendered the stenosis with greater than 70% luminal reduction, and 12 patients showed a decrease in mSA of greater than 1 mm2 which did not, however, result in high-grade luminal narrowing. With regard to factors capable of affecting restenosis rate, there was no relationship between extent of dilatation achieved, local dissection, stenosis configuration or localization, calcification, patient age, sex, duration of symptoms, overweight, cholesterol, triglycerides, HDL, LDL, smoking, hypertension or diabetes. However, a relationship was found between the discontinuation of aspirin or coumadin as a result of GI side effects or bleeding (2% no progression; 20% progression). Thus, antiplatelet therapy appears to be important with respect to long-term results after PTCA.

Angina Pectoris↗

PubMed1985

Effectiveness of molsidomine in the long-term treatment of exertional angina pectoris and chronic congestive heart failure.

Molsidomine, similar to nitrates, improves myocardial blood flow in hypoperfused, poststenotic myocardial regions, reduces left ventricular pressure and volumes, and leads to improvement in impaired regional wall motion. In patients with chronic, stable anginal pectoris who underwent long-term treatment with 2 mg of molsidomine three times daily there were reductions in ST segment depression of 45% and 9% at 1 and 3 hours after administration, respectively, and slight but statistically significant reductions in the rates of anginal attacks and nitrate consumption of 16% and 18%. Administration of 3 mg three times daily did not render more significant effects. Doubling the frequency of administration--that is, 2 mg six times daily--led to reductions in the rates of anginal attacks and nitrate consumption of 38% and 36%, respectively, and 4 mg led to a more marked reduction in ST segment depression of 57%. With administration of 8 mg of sustained-release molsidomine, a prolonged antiischemic effect was documented with reductions in ST segment depression of 74% at 1 hour and 31% at 8 hours after medication. In patients with congestive heart failure, 1 hour after administration of 4 mg of molsidomine there were significant reductions in systolic and diastolic pulmonary artery pressures of 25% and 30%, respectively. After 7 days of continuous treatment with 4 mg of molsidomine four times daily, comparable reductions in pulmonary artery pressure were observed. Thus molsidomine, in adequate dosages, elicits an unequivocal anti-ischemic and antianginal effect as well as a salutary reduction in left ventricular filling pressure.

Angina Pectoris↗

PubMed1985

[Quantitative coronary angiography before and after PTCA. Rate of restenosis, analysis of modifying factors].

In 95 consecutive patients in whom 101 coronary artery stenoses were successfully dilated, angiography was performed before, immediately after and at an average of 6.6 months after the procedures with computer-derived stenosis measurements (based on three-dimensional vessel reconstruction). The results were referenced to an analysis of factors possibly exerting an influence on post-PTCA outcome. In 56 of the 101 dilated stenoses (minimal area prior to PTCA 0.83 +/- 0.57 mm2, after PTCA 4.09 +/- 1.7 mm2), the findings remained essentially unchanged throughout the six-month follow-up. 17 of the 56 dilated stenoses showed a further increase in minimal area as compared with the findings seen immediately after PTCA. A reduction of the minimal area of more than 1 mm2 from that achieved immediately after PTCA, associated with narrowing of the vascular lumen greater than 70% was found in 33 of the 101 stenoses (minimal area before PTCA 0.82 +/- 0.59 mm2, immediately after PTCA 3.92 +/- 1.55 mm2, six months post-PTCA 1.39 +/- 1.27 mm2). In twelve of the 101 stenoses, restenosis amounting to more than 1 mm2 was also observed but without critical compromise of the vascular lumen (minimal area before PTCA 0.81 +/- 0.39 mm2, immediately after PTCA 5.54 +/- 1.28, six months post-PTCA 3.22 +/- 1.43 mm2, corresponding to a mean luminal narrowing of 45 +/- 24%).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

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