Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isosorbide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,549 records · Page 86Linked to original sources
PubMed1991

[Possibilities of potentiating the antianginal action of nitrates by methionine in patients with stable effort angina pectoris].

When given in a single dose, methionine was studied for its effects on the efficacy of isosorbide dinitrate in 8 patients with coronary heart disease. The antianginal and anti-ischemic effects of the agents were evaluated by treadmill exercise testing that had been performed prior to and repeatedly (1, 2, 3, and 6 hours) following a single application of the drug. Methionine in a dose of 1 g failed to produce antianginal and anti-ischemic effects. The concomitant use of isosorbide dinitrate (10 mg) and methionine (1 g) showed significantly pronounced antianginal and anti-ischemic effect than that of isosorbide dinitrate alone. The methionine-induced increase in the effect of isosorbide dinitrate substantially differed in the patients. Thus, methionine is able to potentiate the antianginal and anti-ischemic effect of isosorbide dinitrate.

Angina Pectoris↗
PubMed1976

[Evaluation and comparison of five antianginal treatments by means of a bicycle ergometer exercise test (author's transl)].

The antianginal effect of three drugs (isosorbide dinitrate-nifedipine-oxprenolol) and of two drug associations (isosorbide dinitrate-oxprenolol; nifedipine-oxprenolol) was studied in six patients, by means of a bicycle ergometer exercise test. The study was double blind; placebo was also included in the test. Treatments were administered according to the sequence of a 6 X 6 "balanced" latin-square design. After treatment with isosorbide dinitrate and nifedipine a significant delay in the appearance of angina and of signs of electrocardiographic positivity was observed while after treatment with oxprenolol a significant delay was noticed only in the time of appearance of electrocardiographic positivity. On the contrary, placebo did not determine significant changes in the studied parameters. The best results were achieved with the associations oxprenolol-isosorbide dinitrate and oxprenolol-nifedipine. With these treatments, angina appeared during the exercise test in only two patients while the others had to stop the test because of muscular exhaustion; electrocardiographic signs of ischemia did not appear in one patient. The favourable results of the associations oxprenolol-isosorbide dinitrate and oxprenolol-nifedipine can be explained by the pharmacologic effect of these drugs and by their complementary action.

Adult↗
PubMed1993

Coronary haemodynamics and vasodilatory profile of a potassium channel opener in patients with coronary artery disease.

Previous studies have indicated that nicorandil reduces both preload and afterload, clearly distinguishing nicorandil from conventional nitrates, whose predominant action is that of preload reduction. In association with the decrease in afterload following nicorandil, the contractile responses during isovolumic contraction and relaxation improved significantly, indicating that nicorandil does not demonstrate negative inotropic actions. Furthermore, despite a marked decrease in mean aortic pressure after nicorandil, coronary sinus blood flow remains unchanged. Therefore, coronary vasodilatation must have taken place, while myocardial oxygen consumption decreased significantly. The vasodilatory action of nicorandil on the epicardial coronary artery has also been demonstrated in our previous study. Nicorandil, at a dose of either 20 or 40 mg, induces a significant increase in coronary artery diameter favourably by acting not only on the non-stenotic but also on the stenotic coronary segments. In our recent study, the effects of intracoronary nicorandil (6 mu.kg-1) and isosorbide dinitrate (2 mg) on the epicardial coronary arteries were investigated in patients undergoing coronary angioplasty. In non-stenotic coronary artery segments, the mean coronary diameter increased significantly after either nicorandil (+12%) or isosorbide dinitrate (+17%). In stenotic segments, however, increase in the diameter of the obstructed segment by 20% after intracoronary nicorandil was much more pronounced when compared to that of 8% after isosorbide dinitrate. There was a significant additional increase of 13% in the diameter of the obstructed segment when nicorandil was administered following isosorbide dinitrate, while no such additional effect was observed when isosorbide dinitrate was given after nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗
PubMedDate not supplied

Portal venous flow in response to acute beta-blocker and vasodilatatory treatment in patients with liver cirrhosis.

The drugs currently under investigation in the prevention of recurrent gastrointestinal bleeding in cirrhosis are likely to decrease the portal pressure by means of a primary reduction of portal blood flow. The hemodynamic effects of beta-blocking agents and vasodilatory drugs were noninvasively measured in eight patients with cirrhosis by means of pulsed echo-doppler equipment. Portal caliber, blood velocity and flow were recorded hourly after a single dose of propranolol (40 mg p.o.) or atenolol (100 mg p.o.), and every 5 min after treatment with isosorbide dinitrate (5 mg sublingually). The drugs were administered at random with an interval of 2 days or more. The portal caliber decreased after atenolol, but did not change after propranolol and isosorbide. The blood velocity decreased by 29 +/- 2% 3 hr after propranolol, by 26 +/- 2% 3 hr after atenolol and by 31 +/- 3% 15 min after isosorbide. The portal blood flow decreased by 0.29 +/- 0.03 liters per min after propranolol, by 0.34 +/- 0.06 after atenolol and by 0.26 +/- 0.03 after isosorbide, without any difference among the various treatments. beta-blockers and vasodilatory drugs have comparable effects on portal blood flow. beta 1-selective and nonselective beta-blockers are similarly effective in keeping with the hypothesis that changes in portal blood flow are mainly due to the block of beta 1-receptors.

Adrenergic beta-Antagonists↗
PubMed1994

Direct proof of nitric oxide formation from a nitrovasodilator metabolised by erythrocytes.

When 15N-isosorbide dinitrate was injected into rats, the venous blood showed a 2-line hyperfine structure in the electron spin resonance (ESR) spectra of NO hemoglobin (HbNO), proving generation of 15N-NO. When human blood was mixed with 15N-isosorbide dinitrate anaerobically, ESR spectra showed initially 14N-HbNO, which was then overwhelmed with the increased 15N-HbNO. With deoxygenation of the blood of another 4 male donors without addition of isosorbide dinitrate, two showed 14N-HbNO, but others did not, suggesting varied amount of NO-precursers, nitrosothiols, in human blood. Neither N-ethylmaleimide nor S-hexylglutathione, a glutathione-S-transferase inhibitor, inhibited the formation of UbNO in the hemolysate mixed anaerobically with isosorbide dinitrite.

Adult↗
PubMed1985

Relation of antianginal efficacy of nifedipine to degree of coronary arterial narrowing and to presence of coronary collateral vessels.

Thirty-six patients with chronic stable angina pectoris or with stable and vasospastic components of angina pectoris were classified by coronary arteriographic findings into 4 groups. Patients in group A had a single stenotic coronary artery; patients in groups B, C and D had occluded arteries, but these arteries had been collateralized to varying degrees, and an epicardial coronary steal phenomenon was possible. All patients underwent multiple exercise tests before and after randomized, double-blind, crossover treatment with 20 mg of nifedipine, 20 mg of isosorbide dinitrate, a combination of both, and placebo. Maximal and mean ST-segment depression, occurrence of angina pectoris and heart rate were evaluated. After nifedipine treatment, mean ischemic ST-segment depression was reduced 21% in group A (p less than 0.05), but was not significantly altered in the other groups (group B, 2% decrease; group C, 10% increase; group D, 3% decrease). However, isosorbide dinitrate reduced ST-segment depression significantly in all groups (group A, 29%, p less than 0.001; group B, 18%, p less than 0.01; group C, 19%, p less than 0.05; group D, 33%, p less than 0.05). The combination with nifedipine did not further improve the effect of isosorbide dinitrate. Maximal ST-segment depression and angina pectoris paralleled the changes in mean ST depression during the different medications. Heart rate at rest was not significantly changed after nifedipine treatment in any group, but increased significantly after isosorbide dinitrate treatment in groups B and C (group B, 12%, p less than 0.01; group C, 9%, p less than 0.05); heart rate during exercise did not differ significantly in any group or after any form of medication from placebo.

Adult↗
PubMed1992

Usefulness of pirenzepine, an M1 antimuscarinic agent, for effort myocardial ischemia.

This study evaluated the effect of pirenzepine, an M1 antimuscarinic agent, on exercise duration and ischemic threshold in patients with angiographically documented coronary artery disease and clear-cut ST depression (greater than 0.2 mV, 0.08 second after the J point) during ergometric stress testing. Twenty-five patients, mean age 56 +/- 8 years, underwent 3 randomized multistage bicycle exercise stress tests after intravenous administration of saline solution (2 ml), isosorbide dinitrate (1 mg) and pirenzepine (2 mg). Isosorbide dinitrate, an endothelium-independent coronary dilating agent, was used as a reference drug. Compared with saline, both pirenzepine and isosorbide dinitrate significantly improved time to ischemia (0.15 mV ST-segment depression) from 6.5 +/- 2 to 7.8 +/- 2 and 8.6 +/- 2 minutes and rate-pressure product at ischemia from 21,498 +/- 4,903 to 24,083 +/- 6,692 and 24,547 +/- 5,390 mm Hg.beats/min, respectively. Compared with saline, pirenzepine did not induce significant changes in blood pressure either at rest or during exercise, whereas it decreased resting heart rate from 71 +/- 9 to 60 +/- 11 beats/min (p less than 0.01) and induced a significant increment of heart rate during ischemia from 117 +/- 18 to 126 +/- 21 beats/min (p less than 0.05). Compared with saline, isosorbide dinitrate reduced systolic blood pressure at rest from 132 +/- 12 to 112 +/- 12 mm Hg, increased heart rate at rest from 71 +/- 10 to 84 +/- 16 beats/min and heart rate at ischemia from 117 +/- 18 to 132 +/- 16 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of endothelium and nitrovasodilators on free thiols and disulfides in porcine coronary smooth muscle.

It is hypothesised that the well known development of tolerance to the vasodilating action of organic nitrates is contributed by intracellular depletion of free thiols occurring during repeated treatment with these drugs. Therefore, ring segments of porcine coronary arteries with and without endothelium were treated for 30 min with either vehicle or 100 microM of isosorbide-5-mononitrate, glyceryl trinitrate, S-nitroso-N-acetyl-D,L-penicillamine or N-(3-nitratopivaloyl)-1-cysteine-ethylester (SPM 3672), and the content of histochemically stained free thiols (-SH) and disulfides (S-S-) was measured densitometrically in single smooth muscle cells. In the presence of endothelium the content of -SH in smooth muscle cells of controls (n = 8) gave an extinction of 0.127 +/- 0.013 in the intima and 0.120 +/- 0.010 in the media. The corresponding values for S-S- were 0.684 +/- 0.084 and 0.535 +/- 0.120 (n = 8). Removal of endothelium reduced S-S- to 82.1 +/- 70% and increased -SH to 126.7 +/- 6.7%. Treatment with all nitrates reduced -SH in intact artery segments to a similar degree, ranging between 54.0 +/- 4.4 and 68.7 +/- 4.7% (n = 8-10). In contrast, S-S- content was less affected and reached values between 70.6 +/- 2.8 and 91.6 +/- 6.0% (n = 8-9). As evaluated by tension studies, tolerance developed for glycerol trinitrate and isosorbide-5-mononitrate but not for S-nitroso-N-acetyl-D,L-penicillamine. Induction of tolerance with glycerol trinitrate (0.1 mM) produced a significantly more pronounced attenuation in activity of isosorbide-5-mononitrate than tolerance induction with isosorbide-5-mononitrate (1 mM). In contrast, the potency of SPM 3672 was not reduced in glycerol trinitrate-tolerant arteries. We conclude that, in porcine coronary arteries, an intact endothelium modifies intracellular thiols and disulfides. In addition, nitrate tolerance is associated with, but probably not caused by, thiol depletion.

Analysis of Variance↗
PubMed1990

Relationship between the inhibition of receptor-induced increase in cytosolic free calcium concentration and the vasodilator effects of nitrates in patients with congestive heart failure.

Nitroglycerin, isosorbide dinitrate and sodium nitroprusside, like nifedipine, were found to inhibit the receptor-provoked increase of cytosolic free calcium concentration in human platelets loaded with 2-[(2-amino-5-methylphenoxy)methyl]-6-methoxy-8-aminoquinoline-N,N,N',N' - tetraacetate. Sodium nitroprusside and nitroglycerin induced elevation of cyclic guanosine 3',5'-monophosphate content in platelets which correlated with their calcium-blocking activity. Methylene blue and epinephrine decreased the calcium-blocking effect and the influence of nitroglycerin on cyclic guanosine 3'-5'-monophosphate content, but failed to suppress the inhibitory effect of sodium nitroprusside. Ascorbic acid increased the calcium blocking effect of sodium nitroprusside and its influence on cyclic guanosine 3'-5'-monophosphate content, but did not alter the inhibitory effect of nitroglycerin. In order to evaluate the relationship between the mode of action of nitrates at cellular level and their vasodilatory effectiveness, we studied the circulatory response of the forearm to isosorbide dinitrate and the influence of nitroglycerin on free calcium concentration in the platelets in 10 patients with chronic heart failure. We established a significant positive correlation between the basal values for venous tone and its peak decrease after administration of the 10-mg dose of isosorbide dinitrate. A correlation was also found between the deviation of maximal decrease of venous tone by this dose of isosorbide dinitrate from the regression line (the relationship between the basal venous tone and its lowering by the drug) and mean inhibitory concentration values for nitroglycerin in blocking that proportion of the rise of calcium ion concentration in platelets due to blocking of the platelet-activating factor. Thus, nitrates, like calcium antagonists, inhibit the receptor-provoked calcium supply to the contractile system of the cells so neutralizing the effects of increased concentrations of vasoconstrictors. This suggests that the effectiveness of nitrates appears to be positively related to the contribution of receptor-induced increase of cytosolic free calcium concentration in vasoconstriction together with their capacity to raise cyclic guanosine 3',5'-monophosphate.

Adult↗
PubMed1991

Substance P for evaluation of coronary endothelial function after cardiac transplantation.

The endothelium-dependent vasodilator substance P dilates normal and diseased coronary vessels in humans in vivo and produces a maximal response similar to that seen with intracoronary isosorbide dinitrate. Twelve cardiac transplant recipients underwent intracoronary infusion of substance P after routine annual investigations. All patients were well, with no evidence of rejection and with angiographically normal coronary arteries. Substance P was infused at 2 ml/min for 2 min into the coronary artery, starting at a dose of 1.4 pmol/min and increasing by doubling increments, and followed by isosorbide dinitrate (1 mg/min) infused over 2 min. Coronary artery diameter was measured in 23 vessel segments from 12 transplant recipients. The following doses were infused: saline solution (1 ml/min), substance P (0.7 [three patients], 1.4, 2.8, 5.6, 11.2, 22.4 pmol/min) and isosorbide dinitrate (1 mg/min). The mean percent increase in diameter (+/- SEM) in response to increasing doses of substance P was as follows: 0, 6.5 +/- 2.9%, 10.9 +/- 2.9%, 12.1 +/- 2.9%, 16.5 +/- 2.6%, 19.2 +/- 3.1% and 25.8 +/- 2.2%, respectively. Half maximal dilation was produced with 1.4 to 2.8 pmol/min of substance P; the maximal response (mean percent diameter change) was 22 +/- 2.5%. This was not significantly different from that achieved with isosorbide dinitrate. It is concluded that coronary endothelial function as assessed by response to substance P is preserved in cardiac transplant recipients with angiographically normal coronary arteries. Substance P may be a suitable agent for testing endothelial function in these patients.

Coronary Angiography↗
PubMed1992

Influence of nitrovasodilators on bovine pulmonary histamine release.

The organic nitrates and related nitrovasodilators are relaxants of vascular and airway smooth muscle. Very little information is currently available regarding the influence of nitrates and related nitrovasodilators on pulmonary autacoid release. This study examined the influence of glyceryl trinitrate, isosorbide dinitrate and sodium nitroprusside on histamine release from bovine lung mince. Spontaneous histamine release from bovine lung mince was not altered by 0.1 nM to 1 microM glyceryl trinitrate, isosorbide dinitrate or sodium nitroprusside. Glyceryl trinitrate, isosorbide dinitrate and sodium nitroprusside produced a concentration-dependent decrease in A23187 (10 microM) stimulated histamine release. Glyceryl trinitrate also inhibited histamine liberation following the addition of compound 48/80. Further studies indicated that the inhibitory action of glyceryl trinitrate was reversed by coincubation with the guanylate cyclase inhibitor, methylene blue (10 microM). These findings indicate that glyceryl trinitrate, sodium nitroprusside and isosorbide dinitrate inhibit non-immunologically stimulated pulmonary histamine release and suggest that alterations in guanylate cyclase activity may influence pulmonary histamine release.

Animals↗
PubMed2002

Dual effect of local application of nitric oxide donors in a model of incision pain in rats.

The effects of local application of a cream containing nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine (SNAP) or isosorbide dinitrate were studied in a rat model of incision pain. An incision was made in the plantar aspect of a hind paw and the cream was applied inside the surgical wound. SNAP (1-10%) or isosorbide (2.5-5%) reduced the incision allodynia as measured with von Frey filaments. Higher concentrations produced a smaller or no effect, but SNAP (30%) intensified the allodynia. Allodynia was also intensified by SNAP (5% or 30%) in rats pretreated with intraplantar 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 4 microg), a guanylate cyclase inhibitor. The effect of isosorbide (5%) was prevented by ODQ. The cream containing SNAP released 10- to 20-fold more nitrite than did isosorbide from a macrophage culture. We conclude that local application of drugs generating a low NO concentration reduces incision pain through activation of guanylate cyclase. Drugs generating high NO concentrations, however, intensify pain via a guanylate cyclase-independent mechanism.

Animals↗
PubMed1999

Nitric oxide generation, tachyphylaxis and cross-tachyphylaxis from nitrovasodilators in vivo.

Nitric oxide (NO) increments in exhaled air and changes in mean arterial pressure of anaesthetised rabbits were measured in order to study the NO generation from NO donors and tachyphylaxis in NO formation from nitroglycerin. Continuous infusions of isosorbide dinitrate, isosorbide-5-mononitrate and 3-morpholino-sydnonimine (SIN-1) evoked dose-dependent increases in exhaled NO, paralleled by decrements in mean arterial pressure. Repeated infusions of nitroglycerin resulted in attenuation (P<0.01) of the NO increase from a given dose. Concurrent infusions of isosorbide dinitrate, isosorbide-5-mononitrate or nitroglycerin reduced the amount of NO emanating from the bioconversion of a given dose nitroglycerin as measured in the expired air (P<0.01 for all drugs), indicating cross-tachyphylaxis. SIN-1 did not exhibit such cross-tachyphylaxis. In conclusion, measurements of exhaled NO can be a useful tool for exploration of nitrovasodilator tachyphylaxis. Cross-tachyphylaxis is only shared between some nitrovasodilators and is possibly not due to feedback from the generated NO.

Animals↗
PubMed1991

Reactivity of eccentric and concentric coronary stenoses in patients with chronic stable angina.

Dynamic coronary stenoses may be the cause of a variable angina threshold and rest angina in patients with chronic stable angina. It has been suggested that eccentric but not concentric coronary artery stenoses have the potential for dynamic changes of caliber in response to vasoactive stimuli. The vasomotor response of eccentric (asymmetric narrowing) and concentric (symmetric narrowing) coronary stenoses to ergonovine (20 micrograms intracoronary or 300 micrograms intravenous) and isosorbide dinitrate (1 mg intracoronary) was studied in 51 patients with chronic stable angina. Diameter of reference segments (angiographically normal segments proximal to the stenoses) and that of eccentric (n = 30) and concentric (n = 35) coronary stenoses that ranged from 50% to 90% luminal diameter reduction were measured by computerized quantitative angiography before and after ergonovine and isosorbide dinitrate. Ergonovine reduced stenosis diameter (by greater than or equal to 10%) in 80% of eccentric stenoses and 42% of concentric stenoses (p less than 0.05). Mean (+/- SEM) diameter reduction with ergonovine was 19 +/- 3% and 9.5 +/- 2% for eccentric and concentric stenoses, respectively (p less than 0.05). Isosorbide dinitrate increased coronary diameter (by greater than or equal to 10%) in 70% of eccentric and 43% of concentric stenoses (p less than 0.05). Mean diameter of eccentric stenoses increased from 1.15 +/- 0.05 to 1.35 +/- 0.06 mm after nitrate (18.6 +/- 2.5%), whereas diameter of concentric stenoses increased from 1.05 +/- 0.05 to 1.14 +/- 0.05 mm (10 +/- 2.5%) (p less than 0.05). Average dilation of reference segments with administration of isosorbide dinitrate and constriction with ergonovine were not significantly different in patients with concentric and eccentric stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Interactions between endothelin-I-induced contractions and bronchodilators in human isolated bronchi.

1. The aim of this study was to compare the ability of four different bronchodilators (atrial natriuretic peptide, salbutamol, sodium nitroprusside and isosorbide dinitrate) to reverse and also to protect against contractions evoked by the spasmogens endothelin-1 and methacholine in human isolated bronchial rings. 2. Contractions evoked by either endothelin-1 or methacholine were reversed by atrial natriuretic peptide (10(-9)-10(-6) mol/l), salbutamol (10(-9)-10(-5) mol/l), sodium nitroprusside (10(-9)-10(-5) mol/l) and isosorbide dinitrate (10(-7)-10(-4) mol/l). 3. Sodium nitroprusside produced a significantly (P < 0.05 for data points) greater mean maximal inhibition of endothelin-1-induced tone than methacholine-induced tone; however, the other dilators were equally effective at reversing either endothelin-1- or methacholine-induced contractions. Comparing sodium nitroprusside and salbutamol, sodium nitroprusside was significantly (P < 0.05 for data set) less effective than salbutamol at reversing either endothelin-1- or methacholine-induced contractions. 4. To compare the ability of these bronchodilator substances to protect against spasmogen challenge, cumulative concentration-response curves to either endothelin-1 (10(-10)-3 x 10(-7) mol/l) or methacholine (10(-9)-3 x 10(-4) mol/l) were constructed in the presence and absence of each bronchodilator. Atrial natriuretic peptide, at a concentration of 10(-6) mol/l, significantly attenuated contractions evoked by methacholine. In contrast, contractions evoked by endothelin-1 were enhanced by atrial natriuretic peptide at concentrations of 3 x 10(-7) and 10(-6) mol/l. Preincubation of salbutamol at a concentration of 10(-6) mol/l significantly attenuated methacholine-induced contractions, but responses to endothelin-1 were not altered by preincubation of salbutamol at concentrations of 3 x 10(-7), 10(-6) and 3 x 10(-6) mol/l. Sodium nitroprusside (10(-6) mol/l) and isosorbide dinitrate (3 x 10(-5) mol/l) did not alter responses evoked by subsequent addition of either endothelin-1 or methacholine. At a concentration of 10(-4) mol/l, however, isosorbide dinitrate significantly attenuated endothelin-1-evoked contractions. 5. These results show that drugs which reverse agonist-induced tone in isolated bronchial rings may not necessarily protect against subsequent challenge with this agonist. This suggests that the pharmacology of relaxation may be dissimilar to that of protection.

Albuterol↗
PubMed2004

Pharmacokinetics of three organic nitrates in Chinese healthy male volunteers.

Eighteen Chinese male subjects completed a single-blind, randomized, three-treatment, three-period, cross-over study. In each treatment phase, subjects received a single dose of 20 mg isosorbide dinitrate (CAS 87-33-2, ISDN) intravenous infusion, 20 mg isosorbide 5-mononitrate (CAS 16051-77-7, 5-ISMN) tablet or 20 mg isosorbide 5-mononitrate intravenous infusion. Each consecutive dosing was separated by a washout period of 7 days. Following each dosing, venous blood samples were collected over a period of 16 h. Plasma concentrations of ISDN and its two active metabolites isosorbide 2-mononitrate (2-ISMN), 5-ISMN had been measured by a validated gas chromatographic method. Various pharmacokinetic parameters including AUC0-t, AUC0-infinity, Cmax, tmax, t1/2, Kelm and MRT were determined for the three formulations and found to be in good agreement with literature values. AUC0-t and AUC0-infinity of 5-ISMN tablet and intravenous infusion were 2694 +/- 496 ng x ml(-1) x h vs. 2548 +/- 556 ng x ml(-1) x h and 3266 +/- 624 ng x ml(-1) x h vs. 3178 +/- 769 ng x ml(-1) x h, respectively, and the relative bioavailability of 5-ISMN tablet was 105 +/- 20%. As compared with 5-ISMN intravenous infusion, ISDN can rapidly reach the plateau concentration and metabolize to its active metabolites 5-ISMN and 2-ISMN, which both have vasodilator effect. The results of this study suggest that as evaluated from the pharmacokinetic profiles of the three formulations, 5-ISMN tablet and ISDN intravenous infusion are ideal vasodilators and anti-angina drugs especially in acute conditions due to their rapid onset and long duration of action.

Administration, Oral↗
PubMed1981

[Treatment of congestive cardiac failure with vasodilators (author's transl)].

The possibility of development of tolerance of treatment with vasodilators was investigated in 16 patients with severe chronic congestive cardiac failure. Independent of the primary site of action, the first application of a vasodilator resulted in lowering of pulmonary artery pressure by about 30% (isosorbide dinitrate 40 mg orally in delay-action form and 5 mg sublingually, prazosin 2 mg, dihydralazine 75 mg). Only dihydralazine reduced systemic resistance acutely by 42% and increased cardiac minute volume by 66%. After treatment for 12 days with isosorbide dinitrate delay-action (three times 20 mg), prazosin (three times 2 mg) or dihydralazine (three times 75 mg), there was persistent lowering of the pulmonary artery pressure 16 hours after cessation of treatment only after isosorbide dinitrate (-29%) and dihydralazine (-27%). A decrease of systemic resistance by 11% and an increase of cardiac minute volume by 20% were seen only after dihydralazine. An additional acute application of isosorbide dinitrate or dihydralazine resulted in a further decrease of pulmonary artery pressure (-25% and -11%, respectively). An additional decrease of systemic resistance (-23%) and increase of cardiac minute volume (+18%) were again only seen with dihydralazine. In contrast to the first medication there was no significant change of the pulmonary artery pressure after treatment with prazosin for 12 days.

Adult↗
PubMed1980

[Orally active vasodilators in the management of chronic treatment-resistant cardiac failure (author's transl)].

The acute haemodynamic effects of 40 mg isosorbide dinitrate (10 subjects), 4 mg prazosin (20 subjects) and 50 mg dihydralazine (8 subjects) were compared in 24 patients with the clinical picture of chronic therapy-resistant cardiac failure (NY Heart Association stages III-IV). There was a fall in left-ventricular filling pressure of about 15% and right-atrial mean pressure of 21 and 24%, respectively, with isosorbide dinitrate and prazosin, while there was no change with dihydralazine. Cardiac output rose by 23% with dihydralazine and 20% with prazosin, but remained unchanged with isosorbide dinitrate. These data indicate that a reduction in pulmonary and systemic-venous congestion due to chronic decompensated cardiac failure can be achieved with isosorbide dinitrate and prazosin, while cardiac output can be improved only with prazosin and dihydralazine.

Adult↗