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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
#1
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 2, 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
#2
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 INTERVENTION/OUTCOME: Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization...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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/27888262/search-for-an-animal-model-to-investigate-selective-pulmonary-vasodilation
#8
Bodil Petersen, Thilo Busch, Katharina Noreikat, Lorenz Homeister, Ralf Regenthal, Udo X Kaisers
Pulmonary arterial hypertension is a life-threatening disease with a poor prognosis. Oral treatment with vasodilators is often limited by systemic hypotension. Inhalation of vasodilators offers the opportunity for selective pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled nitric oxide or alternative substances in animal models requires an increased pulmonary vascular tone. The aim of this study was to identify animal models that are suitable for investigating selective pulmonary vasodilation...
November 25, 2016: Laboratory Animals
https://www.readbyqxmd.com/read/27877095/evaluation-of-the-tolerability-of-intermittent-intravenous-sildenafil-in-pediatric-patients-with-pulmonary-hypertension
#9
Robyn A Fender, Ty E Hasselman, Yanzhi Wang, Aaron A Harthan
OBJECTIVES: The primary purpose of this study was to determine the tolerability of intermittent intravenous (IV) sildenafil for the treatment of pulmonary hypertension in pediatric patients. Secondary objectives were to evaluate parameters related to efficacy. METHODS: This was a retrospective chart review from January 2013 to August 2014 of pediatric patients under age 18 years treated with intermittent doses of IV sildenafil for pulmonary hypertension. Patients were excluded if they were over age 18 years or received sildenafil for other indications...
September 2016: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/27869893/-anmco-position-paper-recommendations-for-the-follow-up-of-patients-with-pulmonary-thromboembolism
#10
Carlo D'Agostino, Pietro Zonzin, Iolanda Enea, Michele Massimo Gulizia, Walter Ageno, Piergiuseppe Agostoni, Michele Azzarito, Cecilia Becattini, Amedeo Bongarzoni, Francesca Bux, Franco Casazza, Nicoletta Corrieri, Michele D'Alto, Nicola D'Amato, Andrea Maria D'Armini, Maria Grazia De Natale, Giovanni Di Minno, Giuseppe Favretto, Lucia Filippi, Valentina Grazioli, Gualtiero Palareti, Raffaele Pesavento, Loris Roncon, Laura Scelsi, Antonella Tufano
Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, is the third most common cause of cardiovascular death. The management of the acute phase of VTE is well described in several papers and guidelines, whereas the management of the follow-up of the patients affected from VTE is less defined. This position paper of the Italian Association of Hospital Cardiologists (ANMCO) tries to fill the gap using currently available evidence and the opinion of the experts to suggest the most useful way to manage patients in the chronic phase...
September 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/27834151/in-vitro-and-in-vivo-performance-of-novel-spray-dried-andrographolide-loaded-scleroglucan-based-formulation-for-dry-powder-inhaler
#11
Ashwin J Mali, C Bothiraja, Ravindra R Purohit, Atmaram P Pawar
Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity...
November 9, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27821396/morphine-induced-hearing-loss
#12
Leire Leache, Irene Aquerreta, Libe Moraza, Ana Ortega
PURPOSE: A case of severe bilateral sensorineural hearing loss associated with oral morphine is reported. SUMMARY: A 52-year-old Spanish man was admitted to the intensive care unit with a Glasgow Coma Scale score of 3, a fever, and sudden hearing loss with tinnitus in both ears. His medical history included type 2 diabetes mellitus, depression, sleep disorder, and hypertension. The patient also had pyelonephritis in 2011 and pulmonary embolism in 2014, requiring the placement of an inferior vena cava filter and chronic anticoagulation...
November 15, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27809901/combined-pulmonary-fibrosis-and-emphysema-a-retrospective-analysis-of-clinical-characteristics-treatment-and-prognosis
#13
Lijuan Zhang, Chunling Zhang, Fushi Dong, Qi Song, Fangzhou Chi, Lu Liu, Yupeng Wang, Chunli Che
BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is increasingly acknowledged as a separate syndrome with distinct clinical, physiological and radiological characteristics. We sought to identify physiologic and radiographic indices that predict mortality in CPFE. METHODS: Data on clinical characteristics, pulmonary function, high-resolution computed tomography (HRCT) and treatment were compared between patients with usual interstitial pneumonia (UIP) plus emphysema (CPFE group) and those with IPF alone (IPF group)...
November 3, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27784026/safety-tolerability-and-clinical-effects-of-a-rapid-dose-titration-of-subcutaneous-treprostinil-therapy-in-pulmonary-arterial-hypertension-a-prospective-multi-centre-trial
#14
Ekkehard Grünig, Nicola Benjamin, Tobias J Lange, Ulrich Krueger, Hans Klose, Claus Neurohr, Heinrike Wilkens, Michael Halank, Hans-Jürgen Seyfarth, Matthias Held, Andrew Traube, Michelle Pernow, E Robert Grover, Benjamin Egenlauf, Felix Gerhardt, Thomas Viethen, Stephan Rosenkranz
BACKGROUND: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. OBJECTIVES: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. METHODS: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study...
2016: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/27770771/evaluation-of-efficacy-safety-and-tolerability-of-ambrisentan-in-chinese-adults-with-pulmonary-arterial-hypertension-a-prospective-open-label-cohort-study
#15
Y Huo, Z C Jing, X F Zeng, J M Liu, Z X Yu, G C Zhang, Y Li, Y Wang, Q S Ji, P Zhu, B X Wu, Y Zheng, P P Wang, J Li
BACKGROUND: Although several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH. METHODS: Eligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed)...
October 22, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27756196/pharmacokinetic-drug-evaluation-of-selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#16
Mayank Sardana, Matthew Moll, Harrison W Farber
Management of pulmonary arterial hypertension (PAH) remains challenging even in the contemporary era. Intravenous prostacyclin therapy, while associated with decreased mortality, has practical limitations and requires significant lifestyle modifications. The recently approved long-acting oral IP prostacyclin receptor agonist for treatment of PAH, selexipag, is a non-prostanoid agent that vasodilates, impacts remodeling (anti-proliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (anti-thrombotic), and increases right heart inotropy...
December 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27754197/js-ish-eccr-2-ang-1-7-and-et-1-a-new-partnership
#17
Katie Yates Hood, Hiba Yusuf, Jane E Findlay, Robson A Santos, Carlos H Castro, George S Baillie, Augusto C Montezano, Margaret R MacLean, Rhian M Touyz
ACE2 and Ang-1-7 have been shown to protect against pulmonary hypertension (PH). Mechanisms for this remain unclear. Considering the important role of ET-1 in the pathophysiology of PH and endothelial dysfunction, we questioned whether Ang-(1-7) influences ET-1 signaling in endothelial cells and whether Ang-(1-7) treatment influences the ET-1 system in PH. Human microvascular endothelial cells (HMEC) were stimulated with ET-1 in the absence/presence of Ang 1-7 and showed that Ang 1-7 increased preproET-1 mRNA levels, ET-1 release, and ETBR protein levels...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753873/ish-aha-2-a-case-of-chronic-indolent-pheochromocytoma-which-caused-medically-controlled-hypertension-but-treatment-resistant-diabetes-mellitus
#18
Hae-Young Lee, Chan-Soon Park, Sang-Hoon Na, Kyung-Jin Kim, Chan Joo Lee, Sungha Park
A 47-year-old woman was admitted via emergency department due to dyspnea NYHA Fc II-III aggravated for 2 months after upper respiratory infection. Her height and body weight were 161 cm / 67 kg. Initial vital signs were 110/70 mmHg - 112 BPM - 24/min - 36.5°C. Chest PA showed cardiomegaly and pulmonary congestion (Figure 1). B-natriuretic peptide level was markedly increased (2002 pg/mL, normal range ≤ 100 pg/mL). The echocardiographic examination showed severely dilated LV cavity (61/72 mm) and severe LV systolic dysfunction (EF 28%) with normal left ventricular wall thickness (9/11 mm) (Figure 2)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27687597/-pulmonary-hypertension-definition-classification-and-treatments
#19
Etienne-Marie Jutant, Marc Humbert
Pulmonary hypertension (PH) is a cardio-pulmonary disorder that may involve multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. Its definition is an increase in mean pulmonary artery pressure (mPAP) \hbox{$\geqslant $} ⩾ 25 mmHg at rest, leading to right heart failure and ultimately death. The clinical classification of pulmonary hypertension (PH) categorizes PH into groups which share similar pathophysiological and hemodynamic characteristics and treatments...
2016: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/27683610/an-observational-study-of-inhaled-treprostinil-respiratory-related-safety-in-patients-with-pulmonary-arterial-hypertension
#20
R T Zamanian, D J Levine, R C Bourge, S A De Souza, E B Rosenzweig, H Alnuaimat, C Burger, S C Mathai, N Leedom, K DeAngelis, A Lim, T De Marco
Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory-related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to characterize respiratory-related adverse events (AEs) associated with current or recent treatment with inhaled treprostinil and to compare the incidence of respiratory-related AEs in PAH patients treated with inhaled treprostinil with that in patients treated with other Food and Drug Administration (FDA)-approved PAH therapies...
September 2016: Pulmonary Circulation
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