Effects Of Transdermal Nitroglycerin Research Articles

Nitroglycerin (NTG) plus whole intracranial radiotherapy for brain metastases (BM) in non-small cell cancer patient (NSCLC): A randomized open label, phase II clinical trial.

9114 Background: Hypoxia has been associated with chemo-radioresistance secondary to Vascular Endothelial Growth Factor Receptor induced by Hypoxia Induced Factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in cell lines, and this may have anti-angiogenic, pro-apoptotic, and anti-efflux effects. Particularly, EGFR mutated (EGFRm) tumor cell lines have been shown to overexpress both VEGF and HIF. In this phase II study, we evaluated the effect of transdermal NTG on intracranial objective response rate (iORR), intracranial progression-free survival (ICPFS), and overall survival (OS) of NSCLC patients with BM. Methods: We performed an open-label, phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. iORR and ICPFS were evaluated by MRI by two independent, blinded radiologists. Nitroglycerin was administered using a transdermal 36 mg patch, which released 10 mg in 24 hours with a rest interval of 12 hours from Monday-Friday throughout WBRT administration (10 days). Results: Fifty patients were allocated to the control group, while 46 were allocated to the experimental group (NTG); among these 26 (55.3%) had EGFRm in the control group and 21 (44.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response when compared to controls (56.6% vs. 43.5%; p = 0.024). Additionally, patients who received NTG in addition to WBRT had an independently prolonged ICPFS compared with those who received WBRT alone (27.7 vs. 9.6; HR: 0.470 [95%CI: 0.24-0.89]; p = 0.021). PFS was also positively impacted (HR: 0.519 [95%CI: 0.27-0.98]; p = 0.043). The benefit in terms of iORR and ICPFS (HR: 0.38 [95%CI: 0.16-0.91]; p = 0.030) was particularly important in the EGFRm patient subgroup. No differences were observed in OS. A significantly higher rate of vomiting presented in the NTG arm of the study ( p= 0.016). Conclusions: The concurrent administration of NTG and chemo-radiotherapy improves iORR and ICPFS among NSCLC patients with BM. The benefit is particularly significant in the EGFRm patient subgroup. Clinical trial information: NCT04338867.

Evaluation of the effect of transdermal nitroglycerine patch on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy

Aim: The aim of this study is to evaluate the effect of transdermal nitroglycerin on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy. Materials and Methods : Totally 140 patients of the American Society of Anesthesiologists Grade I or II, posted for abdominal hysterectomy under spinal anesthesia, were randomized to four groups using computer-generated random number list. Group B received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml normal saline and placebo patch, Group BN received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml NS and transdermal nitroglycerin (t-NTG), Group BD received 3 ml of 0.5% hyperbaric bupivacaine with 5 mcg (0.5 ml) dexmedetomidine and placebo patch and Group BDN received 3 ml of 0.5% hyperbaric bupivacaine with 5 μg (0.5 ml) dexmedetomidine and t-NTG patch. Outcomes measured include the total duration of analgesia, onset, and duration of sensory and motor block and any adverse effects. Results: The total duration of analgesia was longest in Group BDN (349.9 ± 40.6 min). It was significantly longer than Group BD (252.3 ± 34.0 min) and Group B and BN (130.5 ± 18.8, 138.3 ± 19.2 min). Time taken for two segment regression was comparable in Group B (79.9 ± 14.4 min) and Group BN (87.1 ± 22.6 min), but it was significantly longer in Group BD (122.5 ± 17.2 min) and Group BDN (136.4 ± 25.5 min). There was no significant difference in other variables between the groups. Conclusion: Transdermal nitroglycerine itself does not exhibit any analgesic potential of its own but, it enhances the analgesic potential of intrathecal dexmedetomidine.

The effect of transdermal nitroglycerin on pain control in diabetic patients with peripheral neuropathy.

BackgroundDespite high prevalence of diabetic peripheral neuropathy there is no definite treatment for the condition. The present study was conducted to assess the efficacy of transdermal nitroglycerin patch in pain control of patients with DPN.MethodsThis randomized, double-blind, crossover study was conducted on 30 patients with symmetric distal peripheral neuropathy and good glycemic control. The patients were randomly assigned to receive nitroglycerin transdermal and placebo patches in two 4-week stages. The severity of pain and other neuropathic sensory symptoms were assessed at the end of each course.ResultsMean reduction of pain severity was more prominent in the NTG group compared to placebo group of the study (p = 0.048) at least during the first phase of the study. Except for mood and sleep, a significant reduction in all Brief Pain Inventory scores was noted in the drug group (all corrected p < 0.05). SF-MPQ also showed the drug patch to be effective in improving different aspects of pain measured using McGill Pain Questionnaire, except for Role–emotional.ConclusionsIt could be concluded that nitroglycerin plasters can effectively help alleviate pain in patients with diabetic neuropathy.Trial registrationIRCT201308223213N1

Effect of Transdermal Nitroglycerin on Insulin Resistance in Healthy Young Men

Objective: There are evidences indicating transdermal nitroglycerin changes the sensitivity of peripheral tissues to the hypoglycemic effect of insulin. In this study we determined effect of continuous application of transdermal nitroglycerin patches in healthy volunteers on development of tolerance to the hypotensive effect of nitroglycerin and hypoglycemic effect of insulin. Materials and methods: The effect of transdermal application of nitroglycerin, as NO donor was studied during 24 hours on blood insulin and glucose level and on blood pressure in healthy, young volunteers. Patches of 0.2 mg/ hour nitroglycerine were administered to young healthy volunteers along 24 hours and Venous blood samples were taken early before and 24 hours after the nitroglycerin. Serum was separated and free zed (-80°C) for insulin and glucose determination. Blood pressure also was determined in 6 hours intervals. Results: Before nitroglycerin patches application mean serum insulin level determined level 9.53 ± 4.37 and after nitroglycerin were 9.18 ± μU/ml which is statistically significant (P>0.05). Fasting blood glucose levels were increased by 6.63 ± 1.9 mg/dl determined 24 hours after nitroglycerine application in comparison with before treatment. The changes observed in blood glucose levels also were statistically significant (P<0.001). Insulin resistance calculated by Homa formula was 1.445 before treatment and 1.540 after nitroglycerin treatment. Conclusion: Transdermal nitroglycerin by doses of 0.2 mg/h causing blood glucose level changes more than change of insulin level indicating change in tissue sensitivity to insulin. The present work was therefore concerned with the possibility that nitrate tolerance impairs the sensitivity of tissues to the hypoglycemic effect of insulin.

Transdermal nitroglycerin in patients with subarachnoid hemorrhage

Delayed ischemic neurological deficit (DIND) following cerebral vasospasm remains a cause for high morbidity and mortality in patients with subarachnoid hemorrhage (SAH). There is experimental and clinical evidence of positive effects of nitric oxide (NO) donors on cerebral vasospasm. We therefore analysed the effect of transdermal nitroglycerin in patients with SAH measuring transcranial Doppler velocities (TCD), cerebral blood flow (CBF) and DIND. Nitroglycerin was used in a target dose of 14 μg/kg/h. TCD assessment was performed daily. CBF measurements were done using the perfusion CT-technique. Blood pressure, volume intake and vasopressor administration, were registered. Nine patients were randomly assigned either to the nitroglycerin group (N-group) and eight patients in the control group (C-group). Mean TCD values in the extracranial portion of the internal carotid artery (ICA) were lower in the N-group (p<0.005). Mean TCD in the middle cerebral arteries (MCA) showed no difference. The Lindegaard ratio was higher in the N-group (p<0.04). CBF in the N-group was higher than in the C-group (p<0.03). Even though nitroglycerin reduces blood pressure and lowers ICA TCD-values and increases the Lindegaard ratio, a higher CBF was measured in the N-group. Thus, nitroglycerin influences the cerebral vascular tone and increases CBF. SAH therapy with nitroglycerin is possible without increasing the risk of DIND. The exact timing of onset, duration and reduction of nitroglycerin administration in respect to the appearance of vasospasm may have a strong impact on the success of such a therapy.

Effect of transdermal nitroglycerin on inflammatory mediators in patients with peripheral atherosclerotic vascular disease

Objective To demonstrate that nitroglycerin improves biological markers of arterial inflammation in patients with peripheral vascular disease. Background Atherosclerosis is an inflammatory disease in which there is an increase in active inflammation markers such as C-reactive protein and other factors released by endothelial cells. Nitroglycerin acts by a chemical liberation of nitric oxide. We have previously published the results from several controlled clinical trials confirming an anti-inflammatory action of nitroglycerin. Methods Forty patients with peripheral vascular disease entered a randomized, double-blind, placebo-controlled pilot study for 6 weeks. Twenty-one patients were treated with continuous application of a transdermal nitroglycerin patch (15 mg/24 hours) on the anterior face of the thigh. Venous blood samples were obtained before treatment and 2 and 6 weeks after. We measured plasma levels of C-reactive protein, cGMP (also intraplatelet cGMP), E-selectin, ICAM, VCAM-1, IL-6, and nitrites/nitrates. Results No biological parameter was modified in the placebo group. On the contrary, nitroglycerin significantly reduced plasma levels of C-reactive protein and sE-selectin and increased the levels of intraplatelet cGMP. Conclusions The results of this preliminary study show that nitroglycerin has an anti-inflammatory action in patients with peripheral vascular disease. This may provide a new therapeutic approach to understanding the efficacy of nitrovasodilators in the improvement of atherosclerotic syndromes.

3629 Effect of transdermal nitroglycerin on inflammatory mediators in patients with peripheral atherosclerotic vascular disease

3629 Effect of transdermal nitroglycerin on inflammatory mediators in patients with peripheral atherosclerotic vascular disease

The effects of transdermal nitroglycerin (nitrol patch) on the uterine and umbilical artery blood flow in preeclampsia: a randomized double blind placebo controlled study

The effects of transdermal nitroglycerin (nitrol patch) on the uterine and umbilical artery blood flow in preeclampsia: a randomized double blind placebo controlled study

Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation

OBJECTIVE: We studied whether transdermal nitroglycerin, a donor of nitric oxide, affects uterine, umbilical, and fetal cerebral blood flow in pregnancies complicated by preeclampsia and impaired uteroplacental blood flow. STUDY DESIGN: Seventeen patients with preeclampsia were treated with a nitroglycerin patch, 10 mg per 24 hours, for three consecutive days between 28 and 36 weeks’ gestation. The uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index were assessed by color Doppler ultrasonography before the start of treatment, daily during treatment, and on the first 2 days after the removal of the last patch. RESULTS: The nitroglycerin patch caused a significant fall in the mean uterine pulsatility index and resistance index that reached its maximum (18% ± 4% and 17% ± 3%, respectively, from baseline) on the last treatment day. After the removal of the last patch, uterine pulsatility index and resistance index rose to the pretreatment value within 12 hours. No significant changes in umbilical or middle cerebral artery pulsatility index and resistance index were observed during treatment. Maternal mean arterial pressure fell from 122 ± 8 to 117 ± 7 mm Hg ( P = .05). CONCLUSION: Transdermal administration of nitroglycerin may offer a potential for treatment for patients with preeclampsia who have increased uteroplacental impedance. (Am J Obstet Gynecol 1998;179:140-5.)

Effect of Transdermal Nitroglycerin or N-Acetylcysteine, or Both, in the Long-Term Treatment of Unstable Angina Pectoris

Objectives. This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris.Background. Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina.Methods. We assessed the efficacy of adding transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy in a randomized, double-blind, placebo-controlled trial involving 200 patients with unstable angina who were followed up for 4 months.Results. Outcome events—death, myocardial infarction or refractory angina requiring revascularization—occurred in 31% of patients receiving nitroglycerin, 42% of those receiving N-acetylcysteine, 13% of those receiving nitroglycerin plus N-acetylcysteine and 39% of those receiving placebo (p = 0.0052). Kaplan-Meier curves showed a higher probability (p < 0.01) of no failure of medical treatment in the group receiving both nitroglycerin and N-acetylcysteine than in those receiving placebo, N-acetylcysteine or nitroglycerin alone. The combination of nitroglycerin and N-acetylcysteine was associated with a high incidence of side effects (35%), mainly intolerable headache, which was almost twice as frequent as in patients receiving nitroglycerin alone.Conclusions. The combination of nitroglycerin and N-acetylcysteine, associated with conventional medical therapy in the long-term treatment of patients with unstable angina, reduces the occurrence of outcome events. However, the high incidence of side effects limits the clinical applicability of this therapeutic strategy at least at the dosage used in the present study.(J Am Coll Cardiol 1997;29:941–7)© 1997 by the American College of Cardiology

Efficacy of Long-Term Administration of Transdermal Nitroglycerin in Asymptomatic Patients with Effort-Induced Silent Myocardial Ischemia

The aim of our study was to investigate the effect of transdermal nitroglycerin (NTG) on effort-induced silent myocardial ischemia in asymptomatic patients treated with beta-blockers or calcium antagonists. The acute effect was compared to two different schedules, continuous (24 h/day) or intermittent (16 h/day), of long-term administration. Ten asymptomatic patients with coronary artery disease and a treadmill test positive for ischemia without angina were enrolled. Both acute (2 days) and long-term (24 days) evaluations were conducted in a randomized, double-blind, crossover fashion. The ergometric parameters were collected on the 1st and the 2nd day of the acute phase (placebo and transdermal NTG, respectively) and at the end of each 12-day period of long-term administration (continuous and intermittent, respectively). Transdermal NTG administration acutely increased (p < 0.05) both time to 1-mm ST segment depression (451 +/- 43.2 vs. 374 +/- 24.1 s) and total exercise time (561.3 +/- 43.2 vs. 419.5 +/- 24.5 s). The acute efficacy was maintained over long-term treatment, regardless of the modality of administration. During continuous and intermittent patch application, time to 1-mm ST segment depression was 437.9 +/- 30.4 and 422 +/- 33.4 s (p = NS vs. acute) and total exercise time was 498.8 +/- 30.4 and 495.1 +/- 33 s (p = NS vs. acute), respectively. Transdermal NTG increases, both acutely and chronically, exercise tolerance in asymptomatic patients with effort-induced silent myocardial ischemia. With the NTG dose we used, tolerance does not seem to be a problem over long-term administration.

The effect of transdermal nitroglycerin on exercise tolerance in relation to patch application time--a meta-analysis.

Disagreeing results have been reported in the many studies on continuous treatment with nitroglycerin patches. The effects on exercise tolerance are partly studied at the end of a 24-hour application period, and partly examined only a few hours after patch renewal. The present meta-analysis estimates the overall efficacy of nitroglycerin patches in trials with and without concomitant antianginal therapy, and investigates if the treatment effect depends on the patch application time. A computed search (MEDLINE) identified 110 publications, of which 17 trials on nitrate patch monotherapy and six trials on combined therapy satisfied the inclusion criteria. Data on "exercise duration" and "ST-segment depression" were converted to a standardized treatment effect size d, and pooled to an overall treatment effect size d+. In tests 2-5 hours after patch renewal, moderate but significant effects of nitrate monotherapy were observed; d+ was 1.20 with regard to "ST-segment depression" and 0.39 with regard to "exercise duration" (both p < 0.0001). In contrast, 24 hours after patch application, the values for d+ were 0.09 (not significant) and 0.36 (p < 0.01), respectively. When adding the results from the six trials on combined therapy, d+ with regard to "exercise duration" was reduced to 0.28 (p < 0.0001) 2-5 hours after renewal and to 0.17 (p = 0.04) after 24 hours. Thus, the efficacy of continuous nitroglycerin patch treatment is moderate but evident during exercise tests 2-5 hours after patch renewal; however, it is reduced after 24 hours of patch application.

Nitrate tolerance in angina pectoris: Effect of transdermal nitroglycerin with a four-hour nitrate-free interval

Nitrate tolerance in angina pectoris: Effect of transdermal nitroglycerin with a four-hour nitrate-free interval

Regional and Systemic Hemodynamic and Humoral Effects of Transdermal Nitroglycerin in Mild Hypertension

Venous distensibility, forearm blood flow (FBF, plethysmographic technique), systemic blood pressure (BP), and derived forearm vascular resistances were measured in 11 borderline-mild hypertensive, otherwise healthy male subjects for a 24-h period during either placebo or transdermally delivered nitroglycerin (NTG 10 mg/24 h). The drug caused arteriolar and venular forearm vasodilation and hypotension which, although persisting throughout the 24-h observation period, reached an apparent maximum during the first hours but later tended to wane. Since NTG plasma levels were constant at that time, the data may suggest development of vascular hyporesponsiveness during continuous exposure to NTG. Venous hematocrit (Hct) decreased during transdermal NTG, indicating the plasma volume expanding action of the drug, apparently dissociated from vasodilation per se. Because no significant changes in either plasma norepinephrine (NE) or plasma renin activity occurred in these subjects, counterregulatory sympathetic or angiotensin II (AII)-mediated vasoconstriction was probably not involved in the hemodynamic action of transdermally delivered NTG.

Mechanisms and therapy of silent myocardial ischemia and the effect of transdermal nitroglycerin

Studies of the mechanisms and characteristics of ischemic heart disease have increasingly documented evidence of myocardial ischemia in the absence of symptoms. Recent work using objective criteria of ischemic events has confirmed that angina pectoris or its equivalents need not accompany true myocardial ischemia, and this appears to be quite common. The impact of these findings on prognosis awaits further study, but preliminary data suggest an improved prognosis for persons in whom coronary artery disease remains asymptomatic compared with symptomatic patients. Further, reduction of silent ischemic events with nitrate therapy may be associated with a more benign subsequent course. Preliminary trials show a reduction of the number, duration and magnitude of silent ischemic events by transdermal nitroglycerin. Ongoing technical innovations in monitoring systems should allow more complete characterization of this syndrome and lead to definition of medical therapy for it.