Effect Of Transdermal Glyceryl Trinitrate Research Articles

Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial

BackgroundThe effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy...

Preterm Labour Management with Glyceryl Trinitrate Patch and Isoxsuprine: A Longitudinal Study

Introduction: Nitric oxide donors in the form of nitroglycerine and β-mimetic drugs (Isoxsuprine hydrochloride) are commonly used in managing preterm labour. It is one of the most challenging obstetric complications encountered by obstetricians, as well as preterm neonates for paediatricians. Preterm labour refers to the onset of uterine contractions of sufficient strength and frequency to effect progressive dilatation and effacement of the cervix between 20 and 37 weeks of gestation. Aim: To compare the effects of transdermal Glyceryl Trinitrate (GTN) with Isoxsuprine in terms of maternal complications, perinatal outcomes, and their tocolytic effectiveness. Materials and Methods: A hospital-based longitudinal study was conducted in the Department of Obstetrics and Gynaecology at JNU Medical College and Research Centre, Jaipur, Rajasthan, India. The study duration of the study was one year, from March 2022 to February 2023. A total number of 100 cases of preterm labour were enrolled and equally divided into two groups: Groups A (GTN patch) and group B (Isoxsuprine) with a defined dosing schedule. Singleton pregnancies with intact membranes and gestational age of 26-36 weeks were included in the study, metting the diagnostic criteria for preterm labour. Both the groups received pharmacological intervention, and outcome measures such as success rate of treatment (i.e., prolongation of labour),. maternal side effects, and foetal outcomes {Neonatal Intensive Care Unit (NICU) admission and Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score) were measured and evaluated. Predefined parameters and other data were tabulated in Microsoft Excel and statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 20.0. The Chi-square test was applied to identify significant differences. Results: The incidence of preterm labour was highest in the age group of 21-30 years (76% in Group A and 70% in Group B) among patients treated with nitroglycerine and isoxsuprine, respectively. The mean prolongation of pregnancy in the nitroglycerine group was 21.42 days, and in the isoxsuprine group, it was 16.22 days (p=0.042). The most common side effect in the nitroglycerine group was headache (60%), while in the isoxsuprine group, it was maternal hypotension (24%). The mean APGAR score in Group A and Group B was 8.18 and 8.06, respectively. It was observed that 24% of newborns in the nitroglycerine group and 36% in the isoxsuprine group required NICU admission. The success rate was 90% in the nitroglycerine group and 80% in the isoxsuprine group. Conclusion: Both drugs were effective in prolonging pregnancy for the first 48 hours, but nitroglycerine was found to be slightly better in terms of success rate. Nitroglycerin was more acceptable to patients with preterm labour, as it did not have to be administered through painful injections.

Route of Feeding as a Proxy for Dysphagia After Stroke and the Effect of Transdermal Glyceryl Trinitrate: Data from the Efficacy of Nitric Oxide in Stroke Randomised Controlled Trial

Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured at day 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ≤6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke.Clinical Trial RegistrationClinical Trial Registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN99414122.

O3-2-1 - Effect of transdermal glyceryl trinitrate, a nitric oxide donor, on global outcome in patients treated within 6 hours of stroke onset

O3-2-1 - Effect of transdermal glyceryl trinitrate, a nitric oxide donor, on global outcome in patients treated within 6 hours of stroke onset

Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria

Cerebral malaria (CM) is associated with low nitric oxide (NO) bioavailability, cerebrovascular constriction, occlusion, and hypoperfusion. Administration of exogenous NO partially prevents the neurological syndrome and associated vascular pathology in an experimental CM (ECM) mouse model. In this study, we evaluated the effects of transdermal glyceryl trinitrate in preventing ECM and, in combination with artemether, rescuing late-stage ECM mice from mortality. The glyceryl trinitrate and/or artemether effect on survival and clinical recovery was evaluated in C57BL/6 mice infected with P. berghei ANKA. NO synthase (NOS) expression in mouse brain was determined by Western blots. Mean arterial pressure (MAP) and pial arteriolar diameter were monitored using a tail-cuff blood pressure system and a cranial window preparation, respectively. Preventative administration of glyceryl trinitrate at 0.025 mg/h decreased ECM mortality from 67 to 11% and downregulated inducible NOS expression in the brain. When administered as adjunctive rescue therapy with artemether, glyceryl trinitrate increased survival from 47 to 79%. The adjunctive therapy caused a sustained reversal of pial arteriolar vasoconstriction in ECM mice, an effect not observed with artemether alone. Glyceryl trinitrate induced a 13% decrease in MAP in uninfected mice but did not further affect MAP in hypotensive ECM mice. Glyceryl trinitrate, when combined with artemether, was an effective adjunctive rescue treatment for ECM. This treatment ameliorated pial arteriolar vasospasm and did not significantly affect MAP. These results indicate that transdermal glyceryl trinitrate has potential to be considered as a candidate for adjunctive therapy for CM.

Acute treatment and prevention of stroke

Nitric oxide (NO) donors are a candidate target for lowering BP in patients with acute stroke. Nitric oxide is a key mediator as a neurotransmitter, in the regulation of cerebral blood flow (CBF) and systemic haemodynamics, and in terms of platelet and leucocyte function. It is potentially neuroprotective 3 and has peripheral vasoactive and cardioprotective properties. A series of three small, phase 2, randomised controlled trials (RCTs) assessed the safety and effects of transdermal glyceryl trinitrate (GTN), an NO donor, in acute or recent stroke. 4,5 Transdermal administration of GTN was chosen as it has the advantages that administration is easy and visible, treatment can be stopped by removal of the patch if necessary and the presence of dysphagia, a common complication of stroke, will not interfere with drug delivery. In the first trial (37 patients randomised in a ratio of 1:1 to active treatment or placebo), GTN reduced 24-hour BP, measured using ambulatory blood pressure monitoring, over the first day, although tachyphylaxis was apparent by day 7. In addition, GTN had no antiplatelet effects, assessed through aggregation and expression of surface adhesion molecules, which means that it can be given to patients with PICH. (The finding on platelet function contrasts with the results of an earlier uncontrolled study of intravenous sodium nitroprusside (SNP), in which platelet function was attenuated.) 6 In the second trial (90 patients randomised in a ratio of 2:1 to active treatment or control), GTN increased vascular compliance but had no effect on large artery blood flow determined using transcranial doppler (TCD) assessment of cerebral blood flow velocity and pulsatility index. 4

The Effect of Transdermal Glyceryl Trinitrate on 24 h Ambulatory Blood Pressure in Acute/Subacute Stroke

High blood pressure is a common complication in acute stroke and is associated with a poor outcome. Aims This study assesses the effects of transdermal glyceryl trinitrate on 24 h ambulatory blood pressure in patients with recent stroke. One hundred and seven patients with acute ischaemic or haemorrhagic stroke were included. The patients had been enrolled in one of two trials of transdermal glyceryl trinitrate (5 mg daily) or placebo/control, and underwent 24 h ambulatory blood pressure monitoring (56 glyceryl trinitrate, 51 control). Ambulatory blood pressure data were analysed using area under the curve for the entire 24 h, and day and night periods. Nocturnal dipping was defined as a decline in systolic blood pressure >10%. Comparisons of blood pressure between groups were performed by analysis of covariance (ANCOVA) with adjustments for trial and baseline measure. In comparison with control, glyceryl trinitrate significantly lowered 24 h blood pressure (systolic blood pressure/diastolic blood pressure 9.4/4.8 mmHg, P < 0.001/0.001, n=104), daytime blood pressure (8.7/4.2, P < 0.001/ <0.001, n=103) and night-time blood pressure (6.9/1.7, P=0.008/0.458, n=86). Only 86 patients (glyceryl trinitrate 45, placebo/control 41) had sufficient night blood pressure measurements to assign dipping status; 28 were dippers (12 glyceryl trinitrate, 16 control) and 58 were nondippers (33 glyceryl trinitrate, 25 control); glyceryl trinitrate significantly lowered systolic but not diastolic blood pressure in both dippers and nondippers. Treatment with glyceryl trinitrate increased the daytime heart rate (4·8 beats/min) but not the night-time heart rate. Patients whose blood pressure did not dip at night had a worse functional outcome at three-months. Transdermal glyceryl trinitrate (5 mg) significantly lowered 24 h blood pressure by 9/5 mmHg (equivalent to a 6% reduction) in both dipping and nondipping patients with acute/subacute stroke. This reduction in blood pressure is clinically relevant and is unlikely to be excessive.

The effects of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure, cerebral and cardiac hemodynamics, and plasma nitric oxide levels in acute stroke

High blood pressure in acute stroke is common and appears to be associated with a poor outcome. Lowering blood pressure might therefore improve outcome, provided that cerebral perfusion is not compromised. We assessed the effects of glyceryl trinitrate (GTN) on cerebral and systemic hemodynamic measures in acute stroke. Ninety patients with acute ischemic or hemorrhagic stroke were randomized within 72 hours of ictus to transdermal GTN given daily for 10 days (either 5 mg, 5 mg for 4 days then 10 mg, or 10 mg) or control. Twenty-four hour blood pressure monitoring, middle cerebral artery blood velocity, cardiac output, augmentation index, and plasma nitric oxide levels were each measured at baseline and then on days 1, 4, 5, and 10. The primary outcome was blood pressure on day 1. We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3% to 6.7% in a dose dependent manner as compared with control (mean, SD): control, 108.8 (15.1) mmHg; 5 mg, 102.5 (13.9) mmHg; 5/10 mg, 103.4 (14.9) mmHg; 10 mg, 101.5 (12.6) mmHg; ( P = .005). Increasing the dose from 5 to 10 mg on day 5 resulted in an overall reduction in blood pressure of 11.4% as compared with leaving the dose at 5 mg ( P = .006). GTN reduced peripheral pulse pressure, central aortic blood pressure, pulse pressure, and augmentation index on day 1. Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere, cardiac output, systemic peripheral resistance, and plasma nitric oxide levels were not altered by GTN. Treatment with GTN was associated with headache: control 0 (0%), GTN 9 (15%) ( P = .027); no negative effect on end-of-treatment death or deterioration, or 3 month death or dependency was discernable. GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index. In contrast, GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres, suggesting that cerebral blood flow did not change. A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted.

The Effect of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Blood Pressure and Platelet Function in Acute Stroke

Background and Purpose: Hypertension is a common medical complication in acute stroke and is associated with a poor outcome. However, no large trials have assessed the effect of lowering blood pressure (BP) on outcome, and it remains unclear how BP should be managed in acute stroke. We assessed, in a double-blind randomised controlled trial, whether the nitric oxide (NO) donor glyceryl trinitrate (GTN, a known systemic and cerebral vasodilator), would lower BP and alter platelet function. Methods: Thirty-seven patients with recent (<5 days) ischaemic or haemorrhagic stroke were randomised by minimisation to 12 days of daily treatment with transdermal GTN or matching placebo patches. Twenty-four-hour ambulatory BP was measured before and during GTN treatment at days 0, 1 and 8. Platelet aggregation and expression of adhesion molecules were assessed at the same time points. Functional outcome (Rankin scale) and case fatality were assessed at 3 months. Analysis was by intention-to-treat. Results: GTN significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8. The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was developing. Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1 and 8, respectively, in the placebo group. GTN had no effect on heart rate, or platelet aggregation or expression of platelet adhesion molecules, including glycoproteins Ia, Ib, IIIa and P-selectin. Additionally, GTN did not alter case fatality or dependency, although the study was not powered for these outcomes. Conclusions: Transdermal GTN, an NO donor, lowered BP by 5–8%, a clinically significant and relevant, but not excessive, degree in patients with acute stroke. However, GTN had no effect on platelet aggregation or expression of adhesion molecules. Since NO donors increase cerebral blood flow in patients with acute ischaemic stroke, GTN may be an appropriate drug for testing the effect of lowering BP on functional outcome.

Maternal and Fetal Cardiovascular Effects of Transdermal Glyceryl Trinitrate and Intravenous Ritodrine

In Brief Objective To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. Methods Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. Results Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI −4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. Conclusion At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor. Transdermal glyceryl trinitrate has significantly fewer maternal and fetal cardiovascular side effects than intravenous ritodrine at doses required for tocolysis.

Maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate and intravenous ritodrine

Objective: To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. Methods: Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. Results: Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI −4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. Conclusion: At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor.

Local Transdermal Glyceryl Trinitrate Has an Antiinflammatory Action on Thrombophlebitis Induced by Sclerosis of Leg Varicose Veins

To test the antiinflammatory and analgesic effects of transdermal glyceryl trinitrate (GTN) the authors carried out a double-blind, randomized, controlled clinical study in 21 patients with mild to moderate leg varicose veins who underwent vein sclerotherapy in both legs. GTN or placebo ointment was applied in a blinded protocol along the surface of the sclerosed vein every eight hours until disappearance of inflammation signs. The varicose vein in one leg was treated with GTN and compared with placebo for the vein of the other leg used as control of thrombophlebitis (TP) signs. Fifteen minutes after first application inflammation signs were observed in all cases. The intensity of inflammation signs was assessed as 26% (10.4 +/- 4.1) in GTN-treated veins and as 61.5% (24.6 +/- 6.3) (P < 0.001) in the placebo-treated veins. One hour later only 63% of cases in the GTN group and all cases in the placebo group showed signs of TP (P < 0.001). The reduction in the intensity of signs at this time was 7.7 +/- 3.9 in the GTN group and 19.7 +/- 6.3 in the placebo group (P < 0.001). All veins in the GTN group were free of signs of TP in less than forty-eight hours. In the placebo group, 45% of veins required more than forty-eight hours for complete disappearance of signs of TP (P < 0.001). The authors conclude that GTN has an antiinflammatory effect in TP induced by sclerotherapy. This action may be related to the nitric oxide released from GTN, through a direct action on the vein and the surrounding inflamed tissue.

The Effect of Transdermal Glyceryl Trinitrate on Exercise Capacity

The Effect of Transdermal Glyceryl Trinitrate on Exercise Capacity