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pulmonary hypertension oral treatment

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https://www.readbyqxmd.com/read/28912026/influence-of-various-therapeutic-strategies-on-right-ventricular-morphology-function-and-hemodynamics-in-pulmonary-arterial-hypertension
#1
Roberto Badagliacca, Amresh Raina, Stefano Ghio, Michele D'Alto, Marco Confalonieri, Michele Correale, Marco Corda, Giuseppe Paciocco, Carlo Lombardi, Massimiliano Mulè, Roberto Poscia, Laura Scelsi, Paola Argiento, Susanna Sciomer, Raymond L Benza, Carmine Dario Vizza
BACKGROUND: In idiopathic pulmonary arterial hypertension (IPAH) treatment goals include improving right ventricular (RV) function, hemodynamics and symptoms to move patients to a low-risk category for adverse clinical outcomes. No data are available on the effect of upfront combination therapy on RV improvement as compared with monotherapy. The aim of this study was to evaluate echocardiographic RV morphology and function in patients affected by IPAH and treated with different strategies...
August 26, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28891448/a-special-focus-on-selexipag-treatment-of-pulmonary-arterial-hypertension
#2
Louise Marqvard Sørensen, Markus Wehland, Marcus Krüger, Ulf Simonsen, Mohamed Zakaria Nassef, Manfred Infanger, Daniela Grimm
BACKGROUND: This review focuses on the treatment of pulmonary arterial hypertension (PAH) with selexipag and compares its drug-related therapeutic effects with those of prostacyclin analogues. METHODS: We searched the relevant literature and summarized the current clinical trials concerning selexipag and PAH. RESULTS: With only few cases per million, PAH is a rare disease, but when untreated it can be life threatening. PAH is linked to elevated levels of endothelin (ET-1) and decreased levels of nitric oxide (NO) and prostacyclin (PGI2)...
September 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28874133/sildenafil-dosed-concomitantly-with-bosentan-for-adult-pulmonary-arterial-hypertension-in-a-randomized-controlled-trial
#3
Carmine Dario Vizza, Pavel Jansa, Simon Teal, Theresa Dombi, Duo Zhou
BACKGROUND: Few controlled clinical trials exist to support oral combination therapy in pulmonary arterial hypertension (PAH). METHODS: Patients with PAH (idiopathic [IPAH] or associated with connective tissue disease [APAH-CTD]) taking bosentan (62.5 or 125 mg twice daily at a stable dose for ≥3 months) were randomized (1:1) to sildenafil (20 mg, 3 times daily; n = 50) or placebo (n = 53). The primary endpoint was change from baseline in 6-min walk distance (6MWD) at week 12, assessed using analysis of covariance...
September 6, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28851689/the-second-generation-pgi2-analogue-treprostinil-fails-to-chemoprevent-tumors-in-a-murine-lung-adenocarcinoma-model
#4
Lori D Dwyer-Nield, Gregory A Hickey, Micah Friedman, Kevin Choo, Debbie G McArthur, Meredith A Tennis, Melissa L New, Mark Geraci, Robert L Keith
Prostacyclin (prostaglandin I2, PGI2) over-production in FVB/N mice prevents the formation of carcinogen and tobacco smoke induced adenomas, and administration of the oral prostacyclin analog iloprost to wild type mice also prevented carcinogen-induced mouse lung adenoma formation. Former smokers taking oral iloprost showed improved bronchial dysplasia histology compared to placebo. Next generation oral prostacyclin analogues, like treprostinil, were developed for treatment of pulmonary arterial hypertension (PAH)...
August 29, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28819824/-update-pulmonary-arterial-hypertension-definitions-diagnosis-therapy
#5
N Sommer, M J Richter, K Tello, F Grimminger, W Seeger, H A Ghofrani, H Gall
The term pulmonary arterial hypertension comprises a group of pulmonary vascular diseases of different etiologies that are characterized by similar precapillary vascular remodeling processes and result in exertional dyspnea and right heart insufficiency. The specific pharmacological treatment approach considers the risk of mortality and phenotypical properties and includes treatment with phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostanoids, as well as with more novel substances, such as a soluble guanylyl cyclase stimulator and an oral prostacyclin receptor agonist...
August 17, 2017: Der Internist
https://www.readbyqxmd.com/read/28813774/pulmonary-embolism-caused-by-popliteal-vein-aneurysm-a-case-report
#6
Kevin Marquez, Kalyan Chakravarthy Potu, Chad Laurich, Randall Lamfers
In this case report, we describe an unusual episode of bilateral submassive pulmonary embolism (PE) caused by a popliteal vein aneurysm (PVA). The development of PE stems from many risk factors including obesity (BMI³ 30 kg/m2), hypertension, cigarette smoking (greater than 25 cigarettes per day), increasing age, surgery, immobility, malignancy, and inherited thrombophilia. A PVA is a rare but significant cause of PE. A 28-year-old male presented to the emergency department with progressive shortness of breath...
March 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28801346/pan-ppar-agonist-iva337-is-effective-in-experimental-lung-fibrosis-and-pulmonary-hypertension
#7
Jerome Avouac, Irena Konstantinova, Christophe Guignabert, Sonia Pezet, Jeremy Sadoine, Thomas Guilbert, Anne Cauvet, Ly Tu, Jean-Michel Luccarini, Jean-Louis Junien, Pierre Broqua, Yannick Allanore
OBJECTIVE: To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). METHODS: IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH...
August 11, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28791664/pharmacokinetics-of-sildenafil-in-children-with-pulmonary-arterial-hypertension
#8
Hugo Juárez Olguín, Hector Osnaya Martínez, Carmen Flores Pérez, Blanca Ramírez Mendiola, Liliana Rivera Espinosa, Juan Luis Chávez Pacheco, Janett Flores Pérez, Ignacio Mora Magaña
BACKGROUND: Recently, sildenafil was introduced to treat pulmonary arterial hypertension (PAH); however, there are currently few studies on the pharmacokinetics of sildenalfil in children. Therefore, we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose. METHODS: Twelve children diagnosed with PAH, consisting of with ten males and two females, were recruited for the study after obtaining written consent from their parents or guardians...
August 8, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28779766/the-discovery-of-macitentan-a-standard-medicinal-chemistry-program
#9
Martin H Bolli
A plethora of properties are typically studied during a medicinal chemistry program and many of these parameters may shape the cascade of compound selection. Given the task to discover a molecule with a profile superior to that of the dual endothelin receptor antagonist bosentan, we tailored our compound profiling cascade to the specific properties that were not optimal in bosentan, namely in vivo efficacy and safety. Contrary to conventional thinking, we therefore focused on corresponding in vivo experiments...
August 9, 2017: Chimia
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#10
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28751848/anmco-position-paper-long-term-follow-up-of-patients-with-pulmonary-thromboembolism
#11
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 pulmonary embolism and deep venous thrombosis, is the third most common cause of cardiovascular death. The management of the acute phase of VTE has already been described in several guidelines. However, the management of the follow-up (FU) of these patients has been poorly defined. This consensus document, created by the Italian cardiologists, wants to clarify this issue using the currently available evidence in VTE. Clinical and instrumental data acquired during the acute phase of the disease are the cornerstone for planning the FU...
May 2017: European Heart Journal Supplements: Journal of the European Society of Cardiology
https://www.readbyqxmd.com/read/28735030/effect-of-bosentan-therapy-in-persistent-pulmonary-hypertension-of-the-newborn
#12
Gunlawadee Maneenil, Anucha Thatrimontrichai, Waricha Janjindamai, Supaporn Dissaneevate
BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) contributes to neonatal hypoxemia and is associated with a high mortality. Some PPHN patients are unresponsive to inhaled nitric oxide (iNO). Bosentan, an oral endothelin-1 receptor antagonist, reduces pulmonary vascular resistance and hence may play a role in the treatment of PPHN. METHODS: A retrospective medical records review was performed in newborns who received oral bosentan as an adjunctive therapy for treatment of PPHN between January 2013 and February 2016 at the neonatal intensive care unit of Songklanagarind Hospital...
July 11, 2017: Pediatrics and Neonatology
https://www.readbyqxmd.com/read/28734831/effects-of-all-oral-anti-viral-therapy-on-hvpg-and-systemic-hemodynamics-in-patients-with-hepatitis-c-virus-associated-cirrhosis
#13
Sabela Lens, Edilmar Alvarado, Zoe Mariño, María-Carlota Londoño, Elba LLop, Javier Martinez, Jose Ignacio Fortea, Luís Ibañez, Xavier Ariza, Anna Baiges, Adolfo Gallego, Rafael Bañares, Angela Puente, Agustín Albillos, Jose Luís Calleja, Xavier Torras, Virginia Hernández-Gea, Jaume Bosch, Cándid Villanueva, Xavier Forns, Juan Carlos García-Pagán
BACKGROUND & AIMS: Patients with hepatitis C virus (HCV)-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH. METHODS: We performed a multicenter prospective study of 226 patients with HCV-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28734808/-congenital-cytomegalovirus-infection-manifesting-as-neonatal-respiratory-distress-in-an-hiv-exposed-uninfected-newborn
#14
A Pham, H El Mjati, N Nathan, F Kieffer, D Mitanchez
BACKGROUND: Cytomegalovirus (CMV) is one of the most common intrauterine infections, affecting approximately 1% of all live births. There are few reports on congenital CMV infections manifesting as isolated pneumonitis. CASE REPORT: We report a case of congenital CMV with neonatal respiratory distress affecting an HIV-exposed uninfected infant. This infant required noninvasive ventilation beginning within the first 15min of life. The initial chest X-ray showed diffuse bilateral ground-glass opacifications...
July 19, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28725332/thyrotoxic-valvulopathy-case-report-and-review-of-the-literature
#15
Keniel Pierre, Sushee Gadde, Bassam Omar, G Mustafa Awan, Christopher Malozzi
We report a 42-year-old female who was admitted for abdominal pain, and also endorsed dyspnea, fatigue and chronic palpitations. Past medical history included asthma, patent ductus arteriosus repaired in childhood and ill-defined thyroid disease. Physical examination revealed blood pressure of 136/88 mm Hg and heart rate of 149 beats per minute. Cardiovascular exam revealed an irregularly irregular rhythm, and pulmonary exam revealed mild expiratory wheezing. Abdomen was tender. Electrocardiogram revealed atrial fibrillation with rapid ventricular response which responded to intravenous diltiazem...
June 2017: Cardiology Research
https://www.readbyqxmd.com/read/28702718/single-center-experience-using-selexipag-in-a-pediatric-population
#16
Roberto Gallotti, Diana E Drogalis-Kim, Gary Satou, Juan Alejos
Pulmonary arterial hypertension (PAH) is a rare and progressive disorder. Current treatment in the pediatric population includes phosphodiesterase 5 inhibitors (PDE-5i), endothelin receptor antagonists (ERA), and both inhaled and intravenous prostacyclin pathway agonists. As of December 22, 2015 the first oral prostacyclin pathway agonist, selexipag (Uptravi(®)), was FDA approved in the US. In this case series, we discuss our single-center experience using selexipag in a pediatric population, composed of both patients with idiopathic PAH, and patients with congenital heart disease and PAH...
July 13, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28686445/discovery-and-optimization-of-chromeno-2-3-c-pyrrol-9-2h-ones-as-novel-selective-and-orally-bioavailable-phosphodiesterase-5-inhibitors-for-the-treatment-of-pulmonary-arterial-hypertension
#17
Deyan Wu, Tianhua Zhang, Yiping Chen, Yadan Huang, Haiju Geng, Yanfa Yu, Chen Zhang, Zengwei Lai, Yinuo Wu, Xiaolei Guo, Jianwen Chen, Hai-Bin Luo
Phosphodiesterase 5 (PDE5) inhibitors have been used as clinical agents to treat erectile dysfunction and pulmonary arterial hypertension (PAH). Herein, we detail the discovery of a novel series of chromeno[2,3-c]pyrrol-9(2H)-one derivatives as selective and orally bioavailable inhibitors against phosphodiesterase 5. Medicinal chemistry optimization resulted in 2, which exhibits a desirable inhibitory potency of 5.6 nM with remarkable selectivity as well as excellent pharmacokinetic properties and an oral bioavailability of 63...
August 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28680576/recommendations-for-the-use-of-oral-treprostinil-in-clinical-practice-a-delphi-consensus-project-pulmonary-circulation
#18
Franck F Rahaghi, Jeremy P Feldman, Roblee P Allen, Victor Tapson, Zeenat Safdar, Vijay P Balasubramanian, Shelley Shapiro, Michael A Mathier, Jean M Elwing, Murali M Chakinala, R James White
Oral treprostinil was recently labeled for treatment of pulmonary arterial hypertension. Similar to the period immediately after parenteral treprostinil was approved, there is a significant knowledge gap for practicing physicians who might prescribe oral treprostinil. Despite its oral route of delivery, use of the drug is challenging because of the requirement for careful titration and management of drug-related adverse effects. We aimed to create a consensus document combining available evidence with expert opinion to provide guidance for use of oral treprostinil...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28676038/efficacy-and-safety-of-oral-sildenafil-in-children-with-down-syndrome-and-pulmonary-hypertension
#19
Maurice Beghetti, Andrzej Rudzinski, Min Zhang
BACKGROUND: Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension...
July 4, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28639216/biocomparison-study-of-adult-and-paediatric-dose-strengths-of-the-prostacyclin-receptor-agonist-selexipag
#20
Margaux Boehler, Shirin Bruderer, Ivan Ulč, Jasper Dingemanse
BACKGROUND AND OBJECTIVES: Selexipag is an oral, non-prostanoid, selective prostacyclin receptor agonist recently marketed for the treatment of pulmonary arterial hypertension (PAH) in adults. Selexipag may also be an effective treatment in children with PAH. The aim of this study was to compare the pharmacokinetics of selexipag and its active metabolite ACT-333679 following single oral administration of one tablet of 200 µg selexipag (Treatment A) vs. 4 paediatric tablets of 50 µg (Treatment B) in healthy adult male subjects...
June 21, 2017: European Journal of Drug Metabolism and Pharmacokinetics
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