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https://www.readbyqxmd.com/read/28524738/selexipag-a-selective-prostacyclin-receptor-agonist-in-pulmonary-arterial-hypertension-a-pharmacology-review
#1
Jesús Honorato Pérez
Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways. Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag...
May 19, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28523018/effect-of-azithromycin-in-combination-with-simvastatin-in-the-treatment-of-chronic-obstructive-pulmonary-disease-complicated-by-pulmonary-arterial-hypertension
#2
Peidong Wang, Jie Yang, Yanwei Yang, Zhixin Ding
OBJECTIVE: To evaluate the effect of azithromycin in combination with simvastatin in the treatment of chronic obstructive pulmonary disease (COPD) complicated by pulmonary arterial hypertension. METHODS: Eighty-six patients who developed COPD and pulmonary arterial hypertension and received treatment from August 2013 to October 2014 were selected and randomly divided into an observation group and a control group using random number table, 43 in each group. Patients in the control group were orally administrated 20 mg of simvastatin, once a day...
March 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28522783/splenic-abcesses-as-infectious-complication-following-127-implantation-of-left-ventricular-asssist-device-case-report
#3
Sławomir Gajda, Anna M Szczepanik, Grzegorz Religa, Andrzej Misiak, Andrzej B Szczepanik
Left ventricular assist device (LVAD) is one of the modern management therapies in patients with advanced heart failure, and it serves as a bridge to heart transplantation or even as destination therapy. However, it is burdened with a high risk of thromboembolic, hemorrhagic, and infectious complications despite prophylactic management. Splenic abscesses, as septic complications following implantation of mechanical ventricular support, have not yet been described in the literature. We report of a patient with severe left ventricular insufficiency (NYHA II/III), pulmonary hypertension, and arrhythmia who underwent implantation of the Heart Ware® pump for left ventricular support with simultaneous tricuspidvalvoplasty, as a bridge therapy to heart transplantation...
February 28, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/28494686/clinical-pharmacology-efficacy-and-safety-of-selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#4
Shirin Bruderer, Noémie Hurst, Tatiana Remenova, Jasper Dingemanse
Introduction Selexipag is the first oral, non-prostanoid, selective prostacyclin receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients. Areas covered: This article reviews the clinical pharmacology, efficacy, and safety of selexipag in the treatment of PAH. Expert opinion: Selexipag is the first oral drug that selectively targets the prostacyclin pathway, and has evidence of long-term efficacy and safety. In the global phase 3 study GRIPHON (NCT01106014) in PAH patients, selexipag significantly reduced the risk of the primary composite outcome of morbidity/mortality (M/M)...
May 11, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28476928/the-selexipag-active-metabolite-act-333679-displays-strong-anti-contractile-and-anti-remodeling-effects-but-low-%C3%AE-arrestin-recruitment-and-desensitization-potential
#5
John Gatfield, Katalin Menyhart, Daniel Wanner, Carmela Gnerre, Lucile Monnier, Keith Morrison, Patrick Hess, Marc Iglarz, Martine Clozel, Oliver Nayler
Prostacyclin (PGI2) receptor (IP receptor) agonists, which are indicated for the treatment of pulmonary arterial hypertension (PAH), increase cytosolic cAMP levels and thereby inhibit pulmonary vasoconstriction, pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular matrix synthesis. Selexipag (Uptravi(®)) is the first non-prostanoid IP receptor agonist, it is available orally and was recently approved for the treatment of PAH. In this study we show that the active metabolite of selexipag and the main contributor to clinical efficacy, ACT-333679 (previously known as MRE-269), behaved as full agonist in multiple PAH-relevant receptor-distal - or downstream - cellular readouts with a maximal efficacy comparable to that of the prototypic PGI2 analog iloprost: In PASMC, ACT-333679 potently induced cellular relaxation (EC50=4...
May 5, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28458514/riociguat-a-soluble-guanylate-cyclase-stimulator-for-the-treatment-of-pulmonary-hypertension
#6
REVIEW
Tian-Yu Lian, Xin Jiang, Zhi-Cheng Jing
Despite advances in treatments and improved survival, patients with pulmonary hypertension still experience poor exercise and functional capacity, which has a significant detrimental impact on their quality of life. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine 3',5'-monophosphate (cGMP) pathway has been shown to play an important role in cardiovascular physiology, especially in vasodilation and pulmonary vascular tone. The oral sGC stimulator riociguat has a dual mode of action on the NO-sGC-cGMP pathway: direct stimulation of sGC independent of NO and indirect simulation via sensitization of sGC to endogenous NO...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28422845/response-to-benzodiazepines-and-the-clinical-course-in-malignant-catatonia-associated-with-schizophrenia-a-case-report
#7
Kazutaka Ohi, Aki Kuwata, Takamitsu Shimada, Toshiki Yasuyama, Yusuke Nitta, Takashi Uehara, Yasuhiro Kawasaki
BACKGROUND: Malignant catatonia (MC) is a disorder consisting of catatonic symptoms, hyperthermia, autonomic instability, and altered mental status. Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments providing rapid relief from MC. This case study reports a detailed clinical course of a case of MC associated with schizophrenia initially diagnosed as NMS that responded successfully to BZDs but not to dantrolene...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28420826/efficacy-and-safety-of-an-orally-administered-selective-prostacyclin-receptor-agonist-selexipag-in-japanese-patients-with-pulmonary-arterial-hypertension
#8
Nobuhiro Tanabe, Satoshi Ikeda, Nobuhiro Tahara, Keiichi Fukuda, Masaru Hatano, Hiroshi Ito, Tomotaka Nakayama, Toshihisa Anzai, Akiyoshi Hashimoto, Teruo Inoue, Kouji Kajinami, Yasuki Kihara, Hideyuki Kinoshita, Koichiro Kuwahara, Toyoaki Murohara, Osamu Okazaki, Satoshi Sakai, Toru Satoh, Yutaka Takeda, Yasuchika Takeishi, Mitsugu Taniguchi, Hiroshi Watanabe, Takeshi Yamamoto, Keiko Yamauchi-Takihara, Koichiro Yoshioka, Shigetake Sasayama
BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28410199/chronic-intratracheal-application-of-the-soluble-guanylyl-cyclase-stimulator-bay-41-8543-ameliorates-experimental-pulmonary-hypertension
#9
Matthieu Amirjanians, Bakytbek Egemnazarov, Akylbek Sydykov, Baktybek Kojonazarov, Ralf Brandes, Himal Luitel, Kabita Pradhan, Johannes-Peter Stasch, Gorden Redlich, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Hossein Ghofrani, Ralph Schermuly
Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389079/safety-and-tolerability-of-subcutaneous-treprostinil-in-newborns-with-congenital-diaphragmatic-hernia-and-life-threatening-pulmonary-hypertension
#10
E Carpentier, S Mur, E Aubry, L Pognon, T Rakza, F Flamein, D Sharma, P Tourneux, L Storme
BACKGROUND: Prolonged pulmonary hypertension (PH) is highly predictive for pulmonary morbidity and death in infants with congenital diaphragmatic hernia (CDH). OBJECTIVES: To report the effects and tolerability of subcutaneous treprostinil in newborns with severe CDH and late life-threatening PH. METHODS: We recorded clinical and echocardiography data before and after starting subcutaneous treprostinil, on patients with severe CDH and late PH, refractory to inhaled nitric oxide and oral sildenafil...
March 28, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28337527/phase-ii-study-of-the-c-met-inhibitor-tivantinib-arq-197-in-patients-with-relapsed-or-relapsed-refractory-multiple-myeloma
#11
Muhamed Baljevic, Shadia Zaman, Veerabhadran Baladandayuthapani, Yan Heather Lin, Claudia Morales de Partovi, Zuzana Berkova, Behrang Amini, Sheeba K Thomas, Jatin J Shah, Donna M Weber, Min Fu, Charles S Cleeland, Xin Shelley Wang, Christine M Stellrecht, Richard E Davis, Varsha Gandhi, Robert Z Orlowski
The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression...
June 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28337251/pentaerythritol-tetranitrate-in-vivo-treatment-improves-oxidative-stress-and-vascular-dysfunction-by-suppression-of-endothelin-1-signaling-in-monocrotaline-induced-pulmonary-hypertension
#12
Sebastian Steven, Matthias Oelze, Moritz Brandt, Elisabeth Ullmann, Swenja Kröller-Schön, Tjebo Heeren, Lan P Tran, Steffen Daub, Mobin Dib, Dirk Stalleicken, Philip Wenzel, Thomas Münzel, Andreas Daiber
Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28262616/protective-effects-of-aloperine-on-monocrotaline-induced-pulmonary-hypertension-in-rats
#13
Fan Wu, Yinju Hao, Jiamei Yang, Wanxia Yao, Yanping Xu, Lin Yan, Yang Niu, Tao Sun, Jianqiang Yu, Ru Zhou
Pulmonary hypertension (PH) is serious, fatal disease which is promoted by oxidative stress. Aloperine have antioxidation effects, which effects on pulmonary arteries remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline and whether these effects are associated with oxidative stress. PH was induced by monocrotaline (60mg/kg), and subsequently oral administration of aloperine (25, 50, 100mg/kg/day). At the end of the experiment, hemodynamic, pathomorphologic, electrocardiographic and echocardiographic data from the rats were obtained...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28257550/tolerability-of-switch-to-macitentan-from-bosentan-in-pulmonary-arterial-hypertension
#14
Zeenat Safdar, Aishwarya Thakur, Adaani Frost
OBJECTIVES: Pulmonary arterial hypertension (PAH) is a progressive disease that can be treated with several medications. Macitentan, an endothelin receptor antagonist (ERA), has received approval as a PAH therapy. We report our data regarding the tolerability in patients with PAH who were switched from bosentan to macitentan. METHODS: At the Baylor Pulmonary Hypertension Program, 24 patients with PAH who had been taking bosentan and were switched to macitentan were identified in this retrospective study...
March 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28228114/efficacy-of-1-5-and-20%C3%A2-mg-oral-sildenafil-in-the-treatment-of-adults-with-pulmonary-arterial-hypertension-a-randomized-double-blind-study-with-open-label-extension
#15
Carmine Dario Vizza, B K S Sastry, Zeenat Safdar, Lutz Harnisch, Xiang Gao, Min Zhang, Manisha Lamba, Zhi-Cheng Jing
BACKGROUND: In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective than the approved 20-mg TID dosage. METHODS: Treatment-naive patients with pulmonary arterial hypertension were randomized to 12 weeks of double-blind sildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID followed...
February 23, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28216071/antiphospholipid-antibodies-disappearance-in-primary-antiphospholipid-syndrome-thrombosis-recurrence
#16
REVIEW
Gabriela Medina, Eduardo Briones-García, María Pilar Cruz-Domínguez, Oscar I Flórez-Durante, Luis J Jara
OBJECTIVE: To evaluate the clinical outcome after aPL (antiphospholipid antibodies) disappearance in primary APS patients. METHODS: From a cohort of 70 patients with primary APS, we selected patients with positive aPL determinations at onset and ≥2 subsequent negative aPL determinations during the last 5years. To corroborate the immunologic profile, we determined IgG/IgM aCL antibodies, IgG/IgM antiβ2GPl, anti-annexin A5 antibodies and lupus anticoagulant (LA)...
April 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28214892/baicalin-attenuates-cardiac-dysfunction-and-myocardial-remodeling-in-a-chronic-pressure-overload-mice-model
#17
Yanqing Zhang, Pingping Liao, Meng'en Zhu, Wei Li, Dan Hu, Siming Guan, Long Chen
BACKGROUND/AIMS: Baicalin has been shown to be effective for various animal models of cardiovascular diseases, such as pulmonary hypertension, atherosclerosis and myocardial ischaemic injury. However, whether baicalin plays a role in cardiac hypertrophy remains unknown. Here we investigated the protective effects of baicalin on cardiac hypertrophy induced by pressure overload and explored the potential mechanisms involved. METHODS: C57BL/6J-mice were treated with baicalin or vehicle following transverse aortic constriction or Sham surgery for up to 8 weeks, and at different time points, cardiac function and heart size measurement and histological and biochemical examination were performed...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28208203/acute-pulmonary-embolism-after-discharge-duration-of-therapy-and-follow-up-testing
#18
Cecilia Becattini, Laura Franco, Giancarlo Agnelli
Pulmonary embolism (PE) is a frequent cause of death and serious disability with a risk extending far beyond the acute phase of the disease. Anticoagulant treatment reduces the risk for death and recurrent VTE after a first PE. The optimal duration of anticoagulation after a first episode of PE remains controversial and should be made on an individual basis, balancing the estimated risk for recurrence without anticoagulant treatment against bleeding risk under anticoagulation. Current recommendations on duration of anticoagulation are based on a 3% per year risk of major bleeding expected during long-term warfarin treatment...
February 2017: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28185800/inhaled-sildenafil-as-an-alternative-to-oral-sildenafil-in-the-treatment-of-pulmonary-arterial-hypertension-pah
#19
Jahidur Rashid, Brijeshkumar Patel, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
The practice of treating PAH patients with oral or intravenous sildenafil suffers from the limitations of short dosing intervals, peripheral vasodilation, unwanted side effects, and restricted use in pediatric patients. In this study, we sought to test the hypothesis that inhalable poly(lactic-co-glycolic acid) (PLGA) particles of sildenafil prolong the release of the drug, produce pulmonary specific vasodilation, reduce the systemic exposure of the drug, and may be used as an alternative to oral sildenafil in the treatment of PAH...
March 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28163023/a-novel-urotensin-ii-receptor-antagonist-kr-36996-improved-cardiac-function-and-attenuated-cardiac-hypertrophy-in-experimental-heart-failure
#20
Kwang-Seok Oh, Jeong Hyun Lee, Kyu Yang Yi, Chae Jo Lim, Byung Kil Park, Ho Won Seo, Byung Ho Lee
Urotensin II and its receptor are thought to be involved in various cardiovascular diseases such as heart failure, pulmonary hypertension and atherosclerosis. Since the regulation of the urotensin II/urotensin II receptor offers a great potential for therapeutic strategies related to the treatment of cardiovascular diseases, the study of selective and potent antagonists for urotensin II receptor is more fascinating. This study was designed to determine the potential therapeutic effects of a newly developed novel urotensin II receptor antagonist, N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl)benzo[b]thiophene-3-carboxamide (KR-36996), in experimental models of heart failure...
March 15, 2017: European Journal of Pharmacology
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