Isosorbide Dinitrate Spray Research Articles

Nitrates administered by spray versus tablet: comparison of coronary vasodilation on CT angiography

To compare the coronary vasodilation effects of spray with those induced by tablet administration in coronary CT angiography (CCTA). A total of 2024 patients who underwent CCTA were identified for this retrospective study, including 828 patients with spray (spray group) and 1169 with tablets (tablet group). Of these, 93 patients underwent CCTA at least twice using both spray and tablets. The number of measurable segments and diameters of all 18 segments was measured. The number of measurable segments was compared between groups. No statistically significant differences were evident between these two groups in terms of clinical characteristics. All coronary segments except the ramus intermedius (RI) and left posterior descending artery (L-PDA) were significantly larger in the spray group than in the tablet group (all p< 0.001). In peripheral and branch vessels, as well as in central and main coronary arteries, the diameters were significantly larger in the spray group than in the tablet group (all p< 0.001). Although not always statistically significant, all coronary segments tended to be more measurable on CCTA with spray than with tablet. In the subgroup that underwent CCTA twice using both spray and tablets, all coronary segments except the RI, obtuse marginal artery 2 (OM2), and L-PDA were significantly larger in the spray group than in the tablet group (all p< 0.05). Lingual isosorbide dinitrate (ISDN) spray was more efficacious than sublingual nitroglycerin (NTG) tablets in coronary vasodilation for CCTA. Therefore, lingual ISDN spray should be preferred over sublingual NTG tablets for CCTA. • Lingual ISDN spray was more efficacious than sublingual NTG tablet for coronary vasodilation in coronary CT angiography, even in elderly patients. • The diameters of all coronary segments except RI and L-PDA were significantly larger, and there were significantly more coronary segments greater than 1.5mm, except RI and L-PDA, in the spray group than in the tablet group in the whole study group. • Even in peripheral and branch vessels, the diameters of coronary arteries were significantly larger in the spray group than in the tablet group, and they were also larger in elderly patients.

ISOSORBIDE DINITRATE SPRAY FOR THE TREATMENT OF DIABETIC FOOT ULCERS

Objective:to evaluate if Isosorbide Dinitrate spray topically applied for management of diabetic foot ulcers take advantage over conventional management using cleaning and metabolic control.Design and method:A randomized, placebo-controlled, double-blinded clinical trial was designed, 34 patients we

Comparison of sublingual isosorbide dinitrate and Valsalva maneuver for detection of obstruction in hypertrophic cardiomyopathy.

IntroductionA left ventricular outflow tract (LVOT) obstruction assessment with a provoking test should be a routine part of the evaluation of patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to compare the utility of the Valsalva maneuver (VM) and sublingual spray application of isosorbide dinitrate (ISDN) for detection of an obstruction.Material and methodsWe prospectively evaluated 81 consecutive HCM patients without severe rest LVOT obstruction (defined as peak rest pressure gradient (PG) ≥ 50 mm Hg). We measured PG at rest, during the VM, after sublingual ISDN spray, and during the VM after ISDN. An obstruction was defined as a PG ≥ 30 mm Hg.ResultsAn obstruction was present in 15 patients (19%) at rest (median and interquartile range of PG 16 (7–26) mm Hg), in 38 patients (47%) during the VM (PG 28 (12–49) mm Hg), in 50 (62%) patients after ISDN (PG 50 (12–79) mm Hg), and in 55 patients (68%) during the VM after ISDN (PG 59 (20–87) mm Hg). The difference in occurrence of obstruction among different provoking tests was statistically significant for all comparisons (p < 0.001, except for the comparison of the ISDN test with the VM during ISDN, p = 0.025).ConclusionsThe ISDN test and the VM are useful screening methods for the detection of an HCM obstruction. Although ISDN appears to be more precise than the VM, the best option is a combination of both methods, which maximizes inducement of LVOT obstruction in patients with HCM.

A New Combination Cream for the Treatment of Severe Neuropathic Pain

A New Combination Cream for the Treatment of Severe Neuropathic Pain

Isosorbide Dinitrate Spray as Therapeutic Strategy for Treatment of Chronic Venous Ulcers

Venous ulcers are the most common form of leg ulcers, which induce lesion because of the loss of substances deposited on the damaged skin. Isosorbide dinitrate is a vasodilator with effects on both arteries and veins and induces opening of vascular layers. The objective is to study the effects of isosorbide dinitrate-spray in patients with chronic venous ulcers. Forty-five patients of both sexes with chronic venous ulcers were randomized to receive isosorbide dinitrate or placebo sprays daily for 3 months. The ulcers were measured and clinical characteristics were taken every 15 days during the treatment. Patients treated with isosorbide dinitrate showed an improvement of the ulcerated area (71.29%) compared with patients treated with placebo (54.35%). The histopathological study indicated an increment in the number of hypertrophic and hyperplasic capillaries. Macroscopically, the isosorbide dinitrate-treatment showed the best results, but it was only during the first 6 weeks of treatment. Patients with chronic venous ulcer receiving isosorbide dinitrate spray showed improvement.

Effects of treatments for symptoms of painful diabetic neuropathy: systematic review

Objective To evaluate the effects of treatments for the symptoms of painful diabetic neuropathy.Design Systematic review.Data sources Articles (English and full text) on double blind randomised trials found by searching...

Potential use of isosorbide dinitrate As a new drug for tilt table test of young adult subject: A study of haemodynamic effects

Vasovagal syncope is a common health problem in young adult population. Tilt table test (TTT) is the only method to diagnose vasovagal syncope. Since isoprenaline as a standard provocative drug of TTT is hard to be found in Indonesia, we study the haemodynamic effect of isosorbide dinitrate (ISDN) which has similar venous pooling effect with isoprenaline. Seventeen young healthy adult subjects (age of 28.6 ± 4.7 year old, and 14 males) underwent TTT using 400 μg ISDN spray sublingually as a provocative drug. The haemodynamic changes were observed during baseline and provocative phase. None of 17 subjects experienced of syncope. Although, the systolic, diastolic, and mean arterial blood pressure were significantly decreased and the heart rate significantly increased after ISDN administration, but the changes were not sufficient to cause syncopal event. In conclusion sublingual ISDN spray during TTT of young healthy adult subject changes haemodynamic measures but did not cause syncope. These results give a reasonable basic for ISDN usage as provocative drug of TTT. (Med J Indones 2006; 15:24-9) Keywords: Syncope, vasovagal, tilt table test, nitrate

Comparison of Isoproterenol Infusion and Nitrate Spray during Provocative Head-Up Tilt Test

Background and Objectives:The head-up tilt test (HUT) is widely used for the diagnosis of vasovagal syncope. To improve the sensitivity of the test, provocation with isoproterenol is frequently used. The aim of this study was to evaluate the values of isosorbide dinitrate spray as a provocation drug in the HUT. Subjects and Methods: Two hundred patients, undergoing baseline HUT (60°for 20 minutes) for suspected vasovagal syncope or presyncope and unexplained dizziness, were enrolled. If the baseline HUT was negative, isosorbide dinitrate (2.5 mg) spray was applied sublingually (group I, n=93), or isoproterenol (3 μg/min) infused (group II, n=93), in a randomized fashion. The values of isosorbide dinitrate and isoproterenol were compared in those patients that developed a positive vasovagal response or who completed the drug-provocative HUT. Results:Syncope was similarly reproduced in both groups (47.7 vs. 41.9%, p>0.05). Type I responses were most common in both groups, and types I and II responses were more common in group I than group II (78.0 vs. 55.6% and 12.2 vs. 5.6%, p<0.05, respectively). The average time to a positive response was longer in group I than group II (8.5±3.4 vs. 6.1±3.6 minutes, p<0.01). The sensitivity and specificity of the drug-provocative HUT were significantly higher in group I than group II (73.5 and 87.5% vs. 58.5 and 71.1%; respectively, p<0.01). The incidence of minor adverse effects were similar in both groups, but serious cardiac side effects were significantly more common in group II than group I (4.3 vs. 0%, p<0.05). Conclusion:Sublingual isosorbide dinitrate spray may be used as a simple, effective and well tolerated provocative drug during HUT. (Korean Circulation J 2005;35:690-695)

Comparison Between Isosorbide Dinitrate in Aerosol and in Tablet Form for the Treatment of Hypertensive Emergencies in the Elderly

Background: Isosorbide dinitrate in spray form is an effective and safe option for the treatment of hypertensive emergencies. The aim of this study was to evaluate whether isosorbide dinitrate spray is as effective and safe as treatment in tablet form for the management of hypertensive emergencies in the elderly. Methods: Forty patients with hypertensive emergencies were randomly divided into two groups of 20 patients each. Group A received 1.25 mg isosorbide dinitrate aerosol upon arrival and a second dose 15 min later when mean systemic arterial pressure (MAP) reduction was <15%. Group B patients received a single 5 mg tablet of sublingual isosorbide dinitrate. Results

Isosorbide dinitrate spray (IDS) is better than isosorbide dinitrate tablets (IDT) in the treatment of hypertensive emergencies (HE)

Isosorbide dinitrate spray (IDS) is better than isosorbide dinitrate tablets (IDT) in the treatment of hypertensive emergencies (HE)

Nitrate induced coronary vasodilatation: differential effects of sublingual application by capsule or spray

BackgroundSublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography.ObjectiveTo compare the...

Pain Scoring – A Method for Assessing Acute Antianginal Therapy Comparison of the Response to Acute Sublingual Administration of an Isosorbide Dinitrate Tablet, Isosorbide Dinitrate Spray and Nitroglycerin Spray in Unstable Angina

It is difficult to assess acute therapeutic intervention therapy, particularly in patients with unstable angina. Our aim was to evaluate the feasibility of a pain-scoring method and to compare the response to sublingual administration of an isosorbide dinitrate (ISDN) tablet, ISDN spray or nitroglycerin (NTG) spray. Pain scoring was assessed by the subjective grading of the patients’ pain severity from 1 to 10. We studied 205 patients (mean age 66 ± 13 years). Pain attenuation, defined as at least 50% reduction in pain intensity, occurred in the ISDN tablet, ISDN spray and NTG spray groups after 360 ± 290, 318 ± 289 and 233 ± 271 s, respectively (p = 0.0005). In conclusion, pain scoring is a feasible and useful clinical method to assess antianginal therapy in unstable angina patients. Sublingual nitrate sprays, particularly NTG, seem to alleviate anginal pain faster than ISDN tablets in this patient population.

Comparison of the Efficacy of Isosorbide Dinitrate Spray and Nitroglycerin Spray in the Regression of Symptoms of Exercise-Induced Moderate Angina Pectoris

This single-centre, controlled, randomised, double-blind, crossover trial was carried out to evaluate the time to recovery from angina pectoris after application of an isosorbide dinitrate (ISDN) spray formulation, which was developed a few years ago (Isoket® spray, Schwarz Pharma, Monheim, Germany), in comparison with that with nitroglycerin (NG) spray in patients with chronic stable angina with documented coronary artery disease. A secondary objective of this trial was to evaluate the safety and tolerability of ISDN spray. 65 patients were randomised to this study; 62 patients were evaluated for efficacy in the intent-to-treat analysis and 28 patients could be evaluated for the per-protocol analysis. Considering the pooled data of the intent-to-treat analysis, patients receiving ISDN spray (2 squirts of 1.25mg ISDN each) recovered after 67.16 seconds, compared with patients administered NG spray treatment (2 squirts of 0.4mg NG each) who recovered after 74.11 seconds (mean difference 6.95 seconds). The Moses 90% confidence interval clearly indicated that the two treatments were equivalent with regard to the clinically relevant difference of 30 seconds as defined in the protocol. In the per-protocol analysis, the pooled data demonstrated that the mean time to recovery from angina pectoris was 63.86 seconds in the ISDN spray-treated patients compared with 71.14 seconds in the NG spray-treated patients. This analysis also indicated that the treatments were equivalent with regard to the clinically relevant difference of 30 seconds as defined in the protocol (Moses 90% confidence interval). In the intent-to-treat analysis the global evaluation of efficacy showed that the investigator rated ISDN spray to be ‘very good’ or ‘good’ in 55 cases and NG spray to be ‘very good’ or ‘good’ in 54 cases. In 56 cases in the ISDN spray group and in 55 cases in the NG spray group treatment was classified as ‘very good’ or ‘good’ by the patients. Comparable results were obtained in the per-protocol analysis. Four adverse events were reported: 2 cases of orthostatic hypotension occurred during the nitrate response test, and 2 patients developed ventricular arrhythmia. In all cases the investigators denied any relationship to the study medication.

Acute Haemodynamic Effects of Isosorbide Dinitrate Spray (1.25 and 2.5mg) in Patients with Coronary Heart Disease

Twelve patients with coronary heart disease were entered into a single-centre double-blind randomised crossover study to compare the effects of 2 dosages of isosorbide dinitrate (ISDN) spray (1.25 and 2.5mg) on haemodynamic parameters and exercise capacity at rest and during and after exercise. After a 36-hour washout period, baseline haemodynamic parameters [pulmonary capillary pressure (PCP), pulmonary arterial pressure (PAP), heart rate and blood pressure] were recorded at rest, under volume load (legs raised), and during and after bicycle ergonometry that followed an increasing workload protocol until the maximum load tolerated by the individual patient was reached. Haemodynamic parameters and ECG were monitored. 10 minutes after PCP had returned to baseline levels, ISDN spray 1.25 or 2.5mg was administered to a buccal, sublingual or lingual site, and the process repeated starting with measurement of resting parameters. A third cycle of measurements began after a 3-hour interval when the patient received the other dosage of ISDN. Both dosages of ISDN spray were well tolerated and no patients withdrew from the study. Both dosages significantly reduced PCP values measured under ergonomic load. There was no statistically or clinically significant difference between the 2 dosages. At rest, PCP was unaffected by either dosage. In conclusion, in this short term study both dosages of ISDN spray improved haemodynamics to the same extent in comparison with initial (untreated) values. The dose-effect relationship could not be assessed because of the high interpatient variation.

Isosorbide Dinitrate Solution Spray in Exercise-Induced Angina Pectoris

The effects of a new formulation of isosorbide dinitrate (ISDN) spray (1.25 and 2.5mg) on exercise-induced anginal symptoms and ischaemic ST-segment changes were studied in a randomised, double-blind, placebo-controlled, crossover study in 20 patients with stable angina pectoris. ISDN spray at both doses reduced ST-segment depression at the highest common workload by 64% (p < 0.001), whereas there was only a slight reduction after administration of placebo (18%). The time to onset of anginal symptoms was increased by 62% with ISDN 1.25mg and 59.5% with ISDN 2.5mg (both p < 0.001) compared with 9% with placebo (p < 0.05). The time to onset of ST depression was also prolonged by 27% and 29% with ISDN 1.25mg and 2.5mg, respectively (both p < 0.001), compared with 5% with placebo (p < 0.05). The time to maximal workload, maximal workload stage and work capacity were also significantly increased by ISDN spray at both doses. There were no statistically significant differences between the effects of ISDN 1.25mg and ISDN 2.5mg, but both dosages were significantly superior to placebo in comparisons of changes in the parameters above. There were no significant changes in heart rate, blood pressure and the double product either at rest or during exercise; there was, however, a small reduction in systolic blood pressure at rest prior to exercise in ISDN-treated patients. There were no serious adverse events. It is concluded that ISDN spray is an effective and safe treatment for the prevention of exercise-induced angina pectoris.

Wider experience with novel isosorbide dinitrate spray

Wider experience with novel isosorbide dinitrate spray

Acute Haemodynamic Effects of a New Formulation of Isosorbide Dinitrate Spray in Patients with Heart Failure

In a randomised double-blind placebo-controlled parallel-group comparison, the haemodynamic effects of a new formulation of isosorbide dinitrate (ISDN) buccal spray in 2 doses (1.25mg and 2.5mg) on pulmonary capillary wedge pressure (PCWP) were investigated in 30 patients with heart failure. Three minutes after administration of either dose of ISDN spray, the onset of a clinically relevant haemodynamic improvement was observed. The maximal reduction from baseline in PCWP was approximately 40% (10mm Hg) 10 minutes after administration of either dose of ISDN spray. This compared with a maximal 14% (3mm Hg) fall in PCWP in placebo-treated patients (p < 0.01). There was a transient 10% fall in systolic blood pressure after ISDN spray at either dose, but no changes in diastolic or mean arterial blood pressure and heart rate compared with placebo-treated patients. There were no significant differences between ISDN spray at 1.25 and 2.5mg in any of the parameters measured. Adverse effects were observed in 2 patients (1 pulmonary oedema with placebo; 1 symptomatic transient hypotension with ISDN 1.25mg). In conclusion, this study clearly shows the rapid beneficial acute haemodynamic effect of ISDN spray in patients with heart failure.

Comparative evaluation of a new formulation of isosorbide dinitrate oral spray and sublingual nitroglycerin tablets

The magnitude and time course of the hemodynamic effect of a new formulation of an aqueous solution of isosorbide dinitrate (ISDN) spray were compared with those of sublingual nitroglycerin (NTG) tablets in 12 patients with chronic congestive heart failure. The patients received, in a random order, ISDN spray, 2.5 mg, or sublingual NTG, 0.8 mg. Hemodynamic measurements were performed before and at 1, 3, 5, 10, 20, 30 and 60 minutes after each drug. The second drug was given only after return of the hemodynamic parameters to baseline, plus a washout period of 2 hours. The hemodynamic variables measured were comparable at baseline. Both drugs produced hemodynamic improvement including a decrease in pulmonary capillary wedge pressure (PCWP), right atrial pressure and systemic and pulmonary vascular resistances. Only ISDN spray significantly increased cardiac output. The onset of action of ISDN spray was significantly more rapid than that of NTG. This was primarily evident in the decrease in PCWP. With ISDN spray the decrease started at 1 minute after administration, and at 3 minutes a decrease of 8.6 mm Hg was already found. The corresponding value for sublingual NTG was 1.6 mm Hg. The difference was highly significant (p < 0.02). The peak effect of ISDN spray on PCWP and right atrial pressure was greater than that of NTG. Thus, the onset of the hemodynamic effect of the new formulation of ISDN spray is much more rapid than that of sublingual NTG tablets. At the doses used, the magnitude of the effect of the ISDN spray on some of the hemodynamic variables is greater than that of sublingual NTG.

Prevention of creatine kinase-MB release in coronary artery disease and pacing-induced myocardial ischemia by isosorbide dinitrate spray

The effect of isosorbide dinitrate (ISDN) spray on release of the isoenzyme creatine kinase-MB (CK-MB) after myocardial ischemia induced by atrial pacing was evaluated in 8 patients with coronary artery disease. Atrial pacing to ischemia (ST-segment depression of ≥1.5 mm for ≥80 ms) resulted in elevation of CK-MB levels in plasma drawn from the coronary sinus, from 1.8 ± 1.5 to 6.8 ± 7.0 ng/ ml (p < 0.001) at 30 minutes after onset of ischemia. When atrial pacing was repeated at the same rate after 1 squirt of ISDN spray, 1.25 mg, the CK-MB levels were not altered despite significant ischemic ST-segment depression. It is concluded that ISDN prevents the process responsible for myocardial release of CK-MB, being either micronecroses or a reversible consequence of ischemia.

A dose-finding study of the hemodynamic effect of isosorbide dinitrate spray in congestive heart failure

A dose-finding study of the hemodynamic effect of a new formulation of isosorbide dinitrate (ISDN) spray was performed in 12 patients with chronic congestive heart failure. Doses of 1.25, 2.5, 5.0 mg and placebo, as 1 squirt, were randomly given to all patients. Hemodynamic measurements were performed by a Swan-Ganz catheter before and at 30 seconds and 1, 5, 10, 20 and 30 minutes after drug administration and every 30 minutes thereafter, until return of hemodynamic variables to baseline. Hemodynamic improvement evident as decreases in right-sided pressures and an increase in cardiac output was observed within 1 minute from administration of ISDN spray, and peaked at 5 minutes. Near maximal effect was achieved by the 2.5-mg dose. Thus, 2.5 mg of ISDN spray (new formulation) produces rapid, near-maximal hemodynamic improvement in patients with congestive heart failure.