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https://www.readbyqxmd.com/read/28090307/hemodynamic-response-to-treatment-of-iron-deficiency-anemia-in-pulmonary-arterial-hypertension-longitudinal-insights-from-an-implantable-hemodynamic-monitor
#1
Muddassir Mehmood, Richa Agarwal, Amresh Raina, Priscilla Correa-Jaque, Raymond L Benza
Despite new therapeutic options, pulmonary arterial hypertension (PAH) remains a progressive disease associated with substantial morbidity and mortality. As such, additional strategies for monitoring and adjunctive management of this disease are important. A 59-year-old woman with scleroderma-associated PAH received an implantable hemodynamic monitor (IHM) as part of a research protocol at our institution. Pulmonary artery pressures, heart rate, and cardiac output (sensor-based algorithm) were measured on a daily basis, and parameters of right ventricular (RV) performance and afterload were calculated...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28090293/relevance-of-angiopoietin-2-and-soluble-p-selectin-levels-in-patients-with-pulmonary-arterial-hypertension-receiving-combination-therapy-with-oral-treprostinil-a-freedom-c2-biomarker-substudy
#2
Manuel J Richter, Ralph Schermuly, Werner Seeger, Youlan Rao, Hossein A Ghofrani, Henning Gall
: Studies have suggested roles for angiopoietin-2 (Ang-2) and soluble P-selectin (sP-selectin) as biomarkers of disease severity and treatment response in pulmonary arterial hypertension (PAH), but additional data are required for validation. We evaluated these biomarkers using data from FREEDOM-C2, in which patients with PAH receiving stable monotherapy or combination therapy were randomized to receive additional treatment with oral treprostinil (up-titrated from 0.25 mg twice daily) or placebo for 16 weeks...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28072531/discovery-of-2-1r-4r-4-4-chlorophenyl-phenyl-carbamoyl-oxy-methyl-cyclohexyl-methoxy-acetate-ralinepag-an-orally-active-prostacyclin-receptor-agonist-for-the-treatment-of-pulmonary-arterial-hypertension
#3
Thuy-Anh Tran, Bryan Kramer, Young-Jun Shin, Pureza Vallar, P Douglas Boatman, Ning Zou, Carleton R Sage, Tawfik Gharbaoui, Ashwin Krishnan, Biman Pal, Sagar R Shakya, Antonio Garrido Montalban, John W Adams, Juan Ramirez, Dominic P Behan, Anna Shifrina, Anthony Blackburn, Tina Leakakos, Yunqing Shi, Michael Morgan, Abu Sadeque, Weichao Chen, David J Unett, Ibragim Gaidarov, Xiaohua Chen, Steve Chang, Hsin-Hui Shu, Shiu-Feng Tung, Graeme Semple
The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28070489/acute-disseminated-histoplasmosis-with-atypical-lymphocytosis-in-an-immunocompetent-host
#4
Ayman Elbadawi, Hamdy M A Ahmed, Hussain Adly, Mohamed A Elkhouly, Samar Abohamed, Ann R Falsey
65 year-old-male presented with a one-week history of high grade fever, fatigue and confusion which began abruptly two days after a cystoscopy procedure. Past medical history included pulmonary sarcoidosis diagnosed by mediastinal lymph biopsy, diabetes and hypertension. On admission he was febrile and confused with stable vital signs. Initial workup included negative Head CT and lumbar puncture. Blood work revealed normal metabolic and liver function tests with progressive anemia, thrombocytopenia and atypical lymphocytosis of 15-20%...
2017: IDCases
https://www.readbyqxmd.com/read/28042638/black-lung-persistent-pulmonary-hypertension-of-the-newborn-saudi-experience-with-sildenafil-and-nitric-oxide
#5
AbdulRahman M Alnemri
To determine the clinical presentation, risk factors, diagnosis, and treatment outcome of Saudi infants with black lung persistent pulmonary hypertension of the newborn (PPHN). Methods: This is a retrospective review of all neonates with PPHN presented to the Armed Force Hospital Southern Region, Kingdom of Saudi Arabia from January 2012 to December 2014. Results: Ten term and near term infants presented with PPHN were included. Maternal diabetes and Down syndrome were the most common identified risk factors for PPHN in the study group...
January 2017: Saudi Medical Journal
https://www.readbyqxmd.com/read/28027769/brain-metabolite-alterations-in-eisenmenger-syndrome-evaluation-with-mr-proton-spectroscopy
#6
Dilek Şen Dokumacı, Ferit Doğan, Ali Yıldırım, Fatıma Nurefşan Boyacı, Erol Bozdoğan, Bülent Koca
OBJECTIVE: Eisenmenger syndrome (ES) is a life-threatening disease characterized by pulmonary hypertension and cyanosis in patients with congenital heart diseases. The aim of this study was to determine the brain metabolite changes in Eisenmenger syndrome compared with a control group using MR proton spectroscopy. METHODS AND MATERIALS: The study included 10 children (3 male, 7 female) with congenital heart diseases and a diagnosis of Eisenmenger syndrome. The control group consisted of 10 healthy volunteer children...
January 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/27990270/recent-advances-in-the-management-of-pulmonary-arterial-hypertension
#7
REVIEW
Halley Tsai, Yon K Sung, Vinicio de Jesus Perez
Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps...
2016: F1000Research
https://www.readbyqxmd.com/read/27989690/comparing-the-efficacy-of-tadalafil-versus-placebo-on-pulmonary-artery-systolic-pressure-and-right-ventricular-function-in-patients-with-beta-thalassaemia-intermedia
#8
Rozita Jalalian, Ali Akbar Moghadamnia, Ahmad Tamaddoni, Soraya Khafri, Mohammadreza Iranian
BACKGROUND: Conventional oral therapies in the management of pulmonary hypertension in people without haemoglobinopathies are of limited value in thalassaemia patients because of toxicity and poor effectiveness. This study was conducted to assess the effect of tadalafil on pulmonary artery pressure and right ventricular systolic function in patients with beta-thalassaemia intermedia. METHODS: Forty-four patients with beta-thalassaemia intermedia with pulmonary hypertension based on transthoracic echocardiography (TTE) were entered in the study...
December 2, 2016: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/27988834/selexipag-a-review-in-pulmonary-arterial-hypertension
#9
Sean T Duggan, Susan J Keam, Celeste B Burness
Selexipag (Uptravi(®)) is an orally active, first-in-class, selective prostacyclin IP receptor agonist. Selexipag was approved recently in the EU for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II or III as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor or as monotherapy in patients who are not candidates for these therapies, and in the USA for the treatment of PAH (WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH...
February 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/27979766/nebulized-solid-lipid-nanoparticles-for-the-potential-treatment-of-pulmonary-hypertension-via-targeted-delivery-of-phosphodiesterase-5-inhibitor
#10
Shaimaa Makled, Noha Nafee, Nabila Boraie
Phosphodiesterase type 5 (PDE-5) inhibitors - among which sildenafil citrate (SC) - play a primary role in the treatment of pulmonary hypertension (PH). Yet, SC can be only administered orally or parenterally with lot of risks. Targeted delivery of SC to the lungs via inhalation/nebulization is mandatory. In this study, solid lipid nanoparticles (SLNs) loaded with SC were prepared and characterized in terms of colloidal, morphological and thermal properties. The amount of drug loaded and its release behavior were estimated as a function of formulation variables...
December 12, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27957707/association-of-oral-endothelin-receptor-antagonists-with-risks-of-cardiovascular-events-and-mortality-meta-analysis-of-randomized-controlled-trials
#11
Yu Pan, Chun Hu, Pei Hua Chen, Yan Hong Gu, Qing Yan Qiao, Li Hua Pan, Dong Chi Zhou, Hui Fang Gu, Shun Kun Fu, Hui Min Jin
BACKGROUND: Endothelin receptor antagonists (ERAs) are widely used in a variety of disorders, including pulmonary artery hypertension, systemic sclerosis, diabetic and kidney diseases, and several tumors. However, reported adverse events, especially increased risks of cardiovascular disease (CVD) morbidity and mortality, have cast doubt on their potential clinical application. Therefore, we conducted this meta-analysis to confirm whether ERAs increased CVD risk and mortality. METHODS: We systematically searched PubMed (1966-2015), EMBASE (1974-2015), ClinicalTrials...
December 13, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27932335/multicentre-randomised-placebo-controlled-trial-of-oral-anticoagulation-with-apixaban-in-systemic-sclerosis-related-pulmonary-arterial-hypertension-the-sphinx-study-protocol
#12
Alicia Calderone, Wendy Stevens, David Prior, Harshal Nandurkar, Eli Gabbay, Susanna M Proudman, Trevor Williams, David Celermajer, Joanne Sahhar, Peter K K Wong, Vivek Thakkar, Nathan Dwyer, Jeremy Wrobel, Weng Chin, Danny Liew, Margaret Staples, Rachelle Buchbinder, Mandana Nikpour
INTRODUCTION: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH...
December 8, 2016: BMJ Open
https://www.readbyqxmd.com/read/27927914/tryptophan-hydroxylase-1-inhibition-impacts-pulmonary-vascular-remodeling-in-two-rat-models-of-pulmonary-hypertension
#13
Robert J Aiello, Patricia-Ann Bourassa, Qing Zhang, Jeffrey Dubins, Daniel R Goldberg, Stéphane De Lombaert, Marc Humbert, Christophe Guignabert, Maria A Cavasin, Timothy A McKinsey, Vishwas Paralkar
Pulmonary arterial hypertension (PAH) is a progressive disease defined by a chronic elevation in pulmonary arterial pressure with extensive pulmonary vascular remodeling and perivascular inflammation characterized by an accumulation of macrophages, lymphocytes, dendritic cells, and mast cells. Although the exact etiology of the disease is unknown, clinical as well as preclinical data strongly implicate a role for serotonin (5-HT) in the process. Here, we investigated the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral 5-HT biosynthesis, in two preclinical models of pulmonary hypertension (PH), the monocrotaline (MCT) rat and the semaxanib (SUGEN, Medinoah, Suzhou, China)-hypoxia rat...
February 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27919660/a-comparison-of-vasodilation-mode-among-selexipag-ns-304-2-4-5-6-diphenylpyrazin-2-yl-isopropyl-amino-butoxy-n-methylsulfonyl-acetamide-its-active-metabolite-mre-269-and-various-prostacyclin-receptor-agonists-in-rat-porcine-and-human-pulmonary-arteries
#14
Chiaki Fuchikami, Kohji Murakami, Koyuki Tajima, Junko Homan, Keiji Kosugi, Kazuya Kuramoto, Michiko Oka, Keiichi Kuwano
Selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl)acetamide]) is a novel, orally available non-prostanoid prostacyclin receptor (IP receptor) agonist that has recently been approved for the treatment of pulmonary arterial hypertension (PAH). We examined the effect of the active metabolite of selexipag, MRE-269, and IP receptor agonists that are currently available as PAH therapeutic drugs on the relaxation of rat, porcine and human pulmonary artery. cAMP formation in human pulmonary artery smooth muscle cells was induced by all test compounds (MRE-269, epoprostenol, iloprost, treprostinil and beraprost sodium) and suppressed by IP receptor antagonists (CAY10441 and 2-[4-(1H-indol-4-yloxymethyl)-benzyloxycarbonylamino]-3-phenyl-propionic acid)...
December 3, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27915325/possible-role-of-sildenafil-citrate-in-the-recurrence-of-neovascularization-in-laser-regressed-aggressive-posterior-rop
#15
Chaitra Jayadev, Phanibhushan Ramasastry, Alia Gul, Anand Vinekar
BACKGROUND: Systemic diseases and their treatment influence aggressive posterior retinopathy of prematurity. CASE CHARACTERISTICS: A premature infant with aggressive posterior retinopathy of prematurity underwent laser treatment with a favourable outcome. She was started on oral sidenafil citrate for pulmonary hypertension. Ten days later she developed neovascularization within the lasered retina. INTERVENTION/OUTCOME: Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization...
November 7, 2016: Indian Pediatrics
https://www.readbyqxmd.com/read/27910060/microrna-delivery-strategies-to-the-lung-in-a-model-of-pulmonary-hypertension
#16
Lin Deng, Andrew H Baker, Angela C Bradshaw
Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells and endothelial cells associated with obliteration of small pulmonary arterioles and formation of plexiform lesions. To date, no curative treatments have been identified for pulmonary arterial hypertension. There are various therapeutic options, including conventional medical therapies and oral, subcutaneous, intravenous, and inhalation delivery. We have previously shown that miR-143/145 knockout can prevent the development of chronic hypoxia-induced pulmonary hypertension (PH) in mice...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27903664/practical-considerations-for-therapies-targeting-the-prostacyclin-pathway
#17
REVIEW
Harrison W Farber, Wendy Gin-Sing
Therapies that target the prostacyclin pathway play a key role in the treatment of both early- and late-stage pulmonary arterial hypertension, and provide significant clinical benefits for patients. A number of agents have been approved, which are administered via intravenous, subcutaneous, inhaled or oral routes. The use of these therapies is associated with practical challenges, relating to the need for up-titration and their routes of administration. We discuss here a number of measures that can be taken to support patients and healthcare professionals in order to address the complexities of using these therapies and to encourage compliance...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27903663/beyond-a-single-pathway-combination-therapy-in-pulmonary-arterial-hypertension
#18
REVIEW
Olivier Sitbon, Sean Gaine
There is a strong rationale for combining therapies to simultaneously target three of the key pathways implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Evidence to support this strategy is growing, and a number of studies have demonstrated that combination therapy, administered as either a sequential or an initial regimen, can improve long-term outcomes in PAH. Dual combination therapy with a phosphodiesterase-5 inhibitor and an endothelin receptor antagonist is the most widely utilised combination regimen...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27895464/selexipag-in-the-treatment-of-pulmonary-arterial-hypertension-design-development-and-therapy
#19
REVIEW
Elizabeth Ashley Hardin, Kelly M Chin
Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27893055/assessment-of-use-vs-discontinuation-of-oral-anticoagulation-after-pulmonary-vein-isolation-in-patients-with-atrial-fibrillation
#20
Sara Själander, Fredrik Holmqvist, J Gustav Smith, Pyotr G Platonov, Milos Kesek, Peter J Svensson, Carina Blomström-Lundqvist, Fariborz Tabrizi, Jari Tapanainen, Dritan Poci, Anders Jönsson, Anders Själander
Importance: Pulmonary vein isolation (PVI) is a recommended treatment for patients with atrial fibrillation, but it is unclear whether it results in a lower risk of stroke. Objectives: To investigate the proportion of patients discontinuing anticoagulation treatment after PVI in association with the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65-74 years, sex category [female]) score, identify factors predicting stroke after PVI, and explore the risk of cardiovascular events after PVI in patients with and without guideline-recommended anticoagulation treatment...
November 23, 2016: JAMA Cardiology
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