In an attempt to resolve some of the controversies concerning the dose requirements and duration of effects of transdermal nitroglycerin (NTG) in patients with heart failure (CHF), the short-term hemodynamic responses to transdermal NTG, in a 20 cm2 self-adhesive patch (10 mg/24 h), were evaluated in 10 patients with severe chronic CHF using a randomized, within-patient, double-blind, placebo-controlled cross-over trial. Serial hemodynamic measurements over 24 h revealed sustained effects that began 1 h after the application of nitroglycerin patch and fully persisted throughout the study. The peak effect occurred at 4 h with the pulmonary capillary wedge pressure decreasing from 33.7 +/- 8.4 to 21.4 +/- 9 mmHg (mean +/- SD) (p less than 0.05) and the cardiac index increasing from 2.5 +/- 0.6 to 3 +/- 0.6 l/min/m2 (p less than 0.01). Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures (from 43.5 +/- 9.5 to 31 +/- 11.4 and from 7.4 +/- 6.6 to 3.8 +/- 4.7 at peak effect, respectively) as well as pulmonary and systemic vascular resistances (from 10.7 +/- 6.6 to 6.5 +/- 3.2 and from 26.2 +/- 5.1 to 22.5 +/- 5.7, respectively). There was no change in heart rate or systemic arterial pressure. These beneficial hemodynamic responses persisted for 24 h. No rebound deterioration occurred upon withdrawal of the nitroglycerin. No significant hemodynamic changes occurred during placebo treatment period. Thus, low doses (10 mg/24 h) of transdermal nitroglycerin induce significant hemodynamic benefit that is sustained for 24 h in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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Redox Biol
January 2025
Department of Pediatrics, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, CA, USA; Lawrence D. Longo, MD Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address:
Repeated use of nitroglycerin results in a loss of its vasodilatory efficacy which limits its clinical use for the treatment of angina pectoris. This tolerance phenomenon is a defining characteristic of all compounds classified as nitrodilators, which includes NTG as well as S-nitrosothiols and dinitrosyl iron complexes. These compounds vasodilate via activation of soluble guanylate cyclase, although they do not release requisite amounts of free nitric oxide (NO) and some do not even cross the plasma membrane.
View Article and Find Full Text PDFDrug Deliv Transl Res
November 2024
Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, 21648, Egypt.
Conventional zolmitriptan (ZOL) has limited oral bioavailability, many adverse effects, and poor membrane penetrability that negatively influences its accessibility to its 5-HT receptor binding pocket, located transmemberanous. This work aimed at preparing transdermal ZOL-nanoformulation (niosomes) to surpass these limitations and to explore novel antimigraine mechanisms for ZOL via modulation of the epigenetically-altered chronification genes (RAMP-1, NPTX-2) or microRNAs and affecting the endocannabinoid CB-1/MAPK pathway. The prepared ZOL niosomes (F) exhibited %EE of 57.
View Article and Find Full Text PDFEur J Neurol
December 2024
Stroke, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Am J Emerg Med
December 2024
Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Introduction: Heart failure (HF) is a common condition prompting presentation to the Emergency Department (ED) and is associated with significant morbidity and mortality. However, there is limited recent large-scale, robust data available on the admission rates, evaluation, and treatment of HF in the ED setting.
Methods: This was a cross-sectional study of ED presentations for HF from 1/1/2016 to 12/31/2023 using the Epic Cosmos database.
Mol Pharm
November 2024
Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, Queensland 4102, Australia.
Transdermal drug delivery systems (TDDS), commonly refered to as "patches", present a nonintrusive technique to provide medication without the need for invasive procedures. These products adhere to the skin and gradually release a specific dosage of medicine at a defined rate into the bloodstream. Compared with other methods of drug delivery, TDDS offer benefits such as reduced invasiveness, convenience for patients, and avoidance of the metabolic processes that occur when drugs are orally consumed.
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