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Treprostinil

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https://www.readbyqxmd.com/read/29650343/safety-efficacy-and-management-of-subcutaneous-treprostinil-infusions-in-the-treatment-of-severe-pediatric-pulmonary-hypertension
#1
Marilyne Levy, Maria-Jesus Del Cerro, Sophie Nadaud, Karunakar Vadlamudi, Elizabeth Colgazier, Jeff Fineman, Damien Bonnet, Ian Adatia
BACKGROUND: Continuous intravenous epoprostenol was the first treatment approved for pulmonary arterial hypertension (PAH) but administration through a central venous line carries risks of thrombosis and sepsis, particularly in children. We sought to evaluate the safety, efficacy and management of subcutaneous (SC) treprostinil in children with PAH. METHODS: Fifty-six children (median age 65, range 1-200 months) were treated with SC treprostinil. Clinical status, echocardiography, NT-proBNP, and site pain and infection were evaluated...
March 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29625570/the-inhibition-of-human-lung-fibroblast-proliferation-and-differentiation-by-gs-coupled-receptors-is-not-predicted-by-the-magnitude-of-camp-response
#2
Maxine J Roberts, Rebecca E Broome, Toby C Kent, Steven J Charlton, Elizabeth M Rosethorne
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel treatment options. There is increasing evidence that the 3', 5' cyclic adenosine monophosphate (cAMP) pathway is an important modulator in the development of fibrosis, with increasing levels of cAMP able to inhibit cellular processes associated with IPF...
April 7, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29610176/pediatric-malignant-atrophic-papulosis
#3
Yung-Chieh Huang, Jiaan-Der Wang, Fang-Yi Lee, Lin-Shien Fu
Malignant atrophic papulosis (MAP), also known as Degos disease, is an extremely rare disease that is characterized by its unique skin presentation (namely, central, porcelain-white atrophic lesions with a telangiectatic rim). MAP has the following 2 variants: cutaneous MAP is manifested in the skin alone, whereas systemic MAP affects the gastrointestinal tract, central nervous system, lungs, and other internal organs. Some patients who presented with only cutaneous symptoms at first may develop systemic symptoms several years later...
April 2018: Pediatrics
https://www.readbyqxmd.com/read/29609511/extended-release-oral-treprostinil-in-the-management-of-pulmonary-arterial-hypertension-clinical-evidence-and-experience
#4
James C Coons, Taylor Miller
Treprostinil diolamine is the first oral prostacyclin approved for the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity. Clinical studies have demonstrated modest benefit as monotherapy, whereas no difference in exercise capacity was observed with combination therapy. However, these trials were limited by subtherapeutic dosing owing to intolerable adverse effects. Prostacyclin-related adverse effects, such as nausea, diarrhea, headache, flushing, and jaw pain, are prevalent. More recent pharmacokinetic and clinical studies illustrate the dose-response relationship and the importance of achieving clinically effective doses...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29588339/selective-prostacyclin-receptor-agonist-selexipag-in-contrast-to-prostacyclin-analogs-does-not-evoke-paradoxical-vasoconstriction-of-rat-femoral-artery
#5
Keith Morrison, Franck Haag, Roland Ernst, Marc Iglarz, Martine Clozel
Selexipag is a selective non-prostanoid prostacyclin (PGI2 ) receptor (IP receptor) agonist that is approved for the treatment of pulmonary arterial hypertension (PAH). In contrast to selexipag, PGI2 analogs used in the clinic are non-selective agonists at prostanoid receptors and can also activate contractile EP3 receptors. Leg pain is a common side effect in patients receiving treatment with PGI2 analogs and peripheral vasoconstriction can be responsible for side effects related to muscular ischemia. This study tested the hypothesis that PGI2 analogs could cause paradoxical vasoconstriction of the femoral artery via EP3 receptor activation but that only vasorelaxation would be observed in response to selexipag and its active metabolite ACT-333679...
March 27, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29582710/dosing-characteristics-of-oral-treprostinil-in-real-world-clinical-practice
#6
Vijay P Balasubramanian, Chad R Messick, Meredith Broderick, Andrew C Nelson
No abstract text is available yet for this article.
January 1, 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29558853/transitioning-parenteral-or-inhaled-treprostinil-to-oral-treprostinil-diolamine-case-series-and-review-of-the-literature
#7
Zachary R Smith, Bryan Kelly, Rana L Awdish, Sara Hegab
Treprostinil diolamine is the first oral dosage preparation of a prostacyclin analogue for use in treatment naive pulmonary arterial hypertension (PAH). This case series and review of the available literature describes the experience of patients with PAH receiving treprostinil by intravenous (IV), subcutaneous (SQ), or inhalation route who were transitioned to treprostinil diolamine. At our institution, 3 patients were transitioned to treprostinil diolamine who received treprostinil administered by each of the alternative routes: IV, SQ, and inhalation...
January 1, 2018: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29525197/perioperative-management-of-pregnant-women-with-idiopathic-pulmonary-arterial-hypertension-an-observational-case-series-study-from-china
#8
Jinglan Zhang, Jiakai Lu, Xiaorui Zhou, Xuefeng Xu, Qing Ye, Qitan Ou, Yanna Li, Jiapeng Huang
OBJECTIVES: The mortality of pregnant women with idiopathic pulmonary arterial hypertension (PAH) is very high. There are limited data on the management of idiopathic PAH during pregnancy. The authors aimed to examine systematically the characteristics of parturient women with idiopathic PAH, to explore the adverse effects of idiopathic PAH on pregnancy outcomes, and to report the multidisciplinary perioperative management strategy from the largest comprehensive cardiac hospital in China...
March 7, 2018: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/29453947/evaluation-of-the-effects-of-rp5063-a-novel-multimodal-serotonin-receptor-modulator-as-single-agent-therapy-and-co-administrated-with-sildenafil-bosentan-and-treprostinil-in-a-monocrotaline-induced-pulmonary-arterial-hypertension-rat-model
#9
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles-E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
Pulmonary arterial hypertension (PAH), a condition that is defined by pulmonary vasculature constriction and remodeling, involves dysfunctional signaling of the serotonin (5-HT) receptors, 5-HT 2/2B/7 . In a rat model of monocrotaline (MCT)-induced PAH, the effectiveness of RP5063 (RP), a dopamine and 5-HT receptor modulator, was evaluated as monotherapy and as an adjunct to standard PAH treatments. After a single 60mg/kg dose of MCT, rats received vehicle (MCT+Veh; gavage twice-daily [b.i.d.]), RP (10mg/kg; gavage b...
February 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29436381/subcutaneous-treprostinil-in-congenital-heart-disease-related-pulmonary-arterial-hypertension
#10
Nika Skoro-Sajer, Christian Gerges, Olga Hajnalka Balint, Dora Kohalmi, Monika Kaldararova, Iveta Simkova, Johannes Jakowitsch, Harald Gabriel, Helmut Baumgartner, Mario Gerges, Roela Sadushi-Kolici, David S Celermajer, Irene Marthe Lang
OBJECTIVE: To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment. METHODS: Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study. RESULTS: Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13)...
February 7, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29421665/inhaled-hexadecyl-treprostinil-provides-pulmonary-vasodilator-activity-at-significantly-lower-plasma-concentrations-than-infused-treprostinil
#11
Richard W Chapman, Zhili Li, Michel R Corboz, Helena Gauani, Adam J Plaunt, Donna M Konicek, Franziska G Leifer, Charles E Laurent, Han Yin, Dany Salvail, Chad Dziak, Walter R Perkins, Vladimir Malinin
INS1009 is a long acting pulmonary vasodilator prodrug of treprostinil (TRE) that is formulated in a lipid nanoparticle for inhaled delivery by nebulization. This study examined the ability of INS1009 to inhibit vasoconstriction in the pulmonary vasculature of rats and dogs and the extent to which local activity within the lung contributes to its activity. Rats received a single dose of INS1009 by nose-only inhalation or were given a continuous intravenous (i.v.) infusion of TRE, followed by an i.v. challenge of the thromboxane mimetic pulmonary vasoconstrictor U46619 and the increase in pulmonary arterial pressure (PAP) was measured...
February 5, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29408757/therapeutic-administration-of-inhaled-ins1009-a-treprostinil-prodrug-formulation-inhibits-bleomycin-induced-pulmonary-fibrosis-in-rats
#12
Michel R Corboz, Jimin Zhang, Daniel LaSala, Keith DiPetrillo, Zhili Li, Vladimir Malinin, Jeremy Brower, Philip J Kuehl, Ted E Barrett, Walter R Perkins, Richard W Chapman
Idiopathic pulmonary fibrosis is a progressive and lethal disease and while there are now two approved drugs (Esbriet® and Ofev®) additional effective treatments are still needed. Recently, prostacyclin analogs such as iloprost and treprostinil (TRE) have been shown to exert some protection against bleomycin-induced pulmonary fibrosis in mice when administered in a prophylactic regimen. In this study, we evaluated the effect of the inhaled treprostinil prodrug hexadecyl-treprostinil (C16TR) formulated in a lipid nanoparticle (INS1009) administered therapeutically in a fibrotic rat model...
February 1, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29348469/treprostinil-inhibits-proliferation-and-extracellular-matrix-deposition-by-fibroblasts-through-camp-activation
#13
Christopher Lambers, Michael Roth, Peter Jaksch, Gabriella Muraközy, Michael Tamm, Walter Klepetko, Bahil Ghanim, Feng Zhao
Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lung donors were stimulated by PDGF, or TGF-β1, or the combination...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310475/human-factors-and-usability-engineering-in-the-development-of-smt-101-for-the-treatment-of-pulmonary-arterial-hypertension
#14
Peter Noymer, Assaf Shaked, Kay Newell
BACKGROUND: SMT-101, a novel, proprietary, water-resistant wearable infusion pump prefilled with a preset dosage of treprostinil, was designed to address many of the administration-related shortcomings of existing parenteral therapy for pulmonary arterial hypertension (PAH). The objective of the human factors (HF) program was to demonstrate that the SMT-101 system is safe and effective when used by patients with PAH, their caregivers, or healthcare providers. METHODS: The HF program for SMT-101 consisted of 8 studies (148 participants): an ethnographic study, an online survey of patients with PAH, 4 formative studies, a study of the instructions for use (IFU), and a summative study for validation...
April 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29275453/inhaled-treprostinil-in-pulmonary-hypertension-associated-with-lung-disease
#15
Mariana Faria-Urbina, Rudolf K F Oliveira, Manyoo Agarwal, Aaron B Waxman
PURPOSE: Pulmonary hypertension (PH) in the setting of parenchymal lung disease adversely affects quality of life and survival. However, PH-specific drugs may result in ventilation/perfusion imbalance and currently, there are no approved PH treatments for this patient population. In the present retrospective study, data from 22 patients with PH associated with lung disease treated with inhaled treprostinil (iTre) and followed up clinically for at least 3 months are presented. METHODS: PH was defined by resting right heart catheterization as a mean pulmonary artery pressure (mPAP) ≥ 35 mmHg, or mPAP ≥ 25 mmHg associated with pulmonary vascular resistance ≥ 4 Woods Units...
April 2018: Lung
https://www.readbyqxmd.com/read/29199910/impact-of-four-times-daily-dosing-of-oral-treprostinil-on-tolerability-and-daily-dose-achieved-in-pulmonary-hypertension
#16
James C Coons, Cheryl Bunner, David C Ishizawar, Michael G Risbano, Belinda Rivera-Lebron, Michael A Mathier, Stephen Y Chan, Marc A Simon
Oral treprostinil (TRE) is a prostacylin that is approved for the treatment of patients with pulmonary arterial hypertension (PAH). Dosing is approved for two or three times daily (t.i.d.); however, adverse effects, including gastrointestinal-related symptoms, may limit the ability to reach optimal doses. We report our experience with a four times daily (q.i.d.) regimen of oral TRE for goal-directed therapy of PAH. We describe three patients that were transitioned from infusion or inhaled TRE to oral TRE with initial t...
January 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29195500/an-implantable-pump-lenus-pro%C3%A2-in-the-treatment-of-pulmonary-arterial-hypertension-with-intravenous-treprostinil
#17
Marcin Kurzyna, Katarzyna Małaczyńska-Rajpold, Andrzej Koteja, Agnieszka Pawlak, Łukasz Chrzanowski, Michał Furdal, Zbigniew Gąsior, Wojciech Jacheć, Bożena Sobkowicz, Justyna Norwa, Tatiana Mularek-Kubzdela, Adam Torbicki
BACKGROUND: Subcutaneous treprostinil is a prostacyclin analogue used to treat pulmonary arterial hypertension (PAH). Due to local pain it can cause a deterioration of heart related quality of life (HRQoL) or even abandonment of treatment. The aim of this paper was to assess the feasibility of treatment with intravenous treprostinil administered by means of the Lenus Pro® implantable pump. METHODS: This was a retrospective, multi-center study involving 12 patients (8 females) with PAH treated with a subcutaneous infusion of treprostinil with intolerable pain at the infusion site...
December 2, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29145311/pulmonary-hypertension-as-a-manifestation-of-mitochondrial-disease-a-case-report-and-review-of-the-literature
#18
REVIEW
Shan Xu, Xiaoling Xu, Jisong Zhang, Kejing Ying, Yuquan Shao, Ruifeng Zhang
BACKGROUND: Mitochondrial diseases are a group of multisystem heterogeneous diseases caused by pathologic dysfunction of the mitochondrial respiratory chain. A wide range of clinical expression has been described. However, pulmonary hypertension has rarely been described in association with mitochondrial disease until the past decade, and there is no currently recognized treatment for the pulmonary hypertension complicated with mitochondrial disorder. PATIENT CONCERNS: We reported the case of a 15-year-old boy who presented with shortness of breath and exercise limitation after a cold, and the diagnosis of pulmonary hypertension was confirmed by right heart catheter...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29076824/preliminary-results-from-a-nationwide-adult-cardiology-perspective-for-pulmonary-hypertension-registry-on-clinical-outcome-and-survival-in-pulmonary-hypertension-groups-simurg
#19
Cihangir Kaymaz, Bülent Mutlu, M Serdar Küçükoğlu, Barış Kaya, Bahri Akdeniz, Burçak Kılıçkıran Avcı, Enbiya Aksakal, Mehmet Akbulut, Zehra Atılgan Arıtürk, Sümeyye Güllülü, Gülten Aydoğdu Taçoy, Meral Kayıkçıoğlu, Sanem Nalbantgil, Cihan Örem, Hatice Betül Erer, Murat Yüce, Necip Ermiş, Omaç Tüfekçioğlu, Mesut Demir, Mehmet Birhan Yılmaz, Mehmet Güngör Kaya, Hakan Kültürsay, Zeki Öngen, Lale Tokgözoğlu
OBJECTIVE: The present study was designed to evaluate the characteristics of pulmonary hypertension (PH) and adult cardiology practice patterns for PH in our country. METHODS: We evaluated preliminary survey data of 1501 patients with PH (females, 69%; age, 44.8±5.45) from 20 adult cardiology centers (AdCCs). RESULTS: The average experience of AdCCs in diagnosing and treating patients with PH was 8.5±3.7 years. Pulmonary arterial hypertension (PAH) was the most frequent group (69%) followed by group 4 PH (19%), group 3 PH (8%), and combined pre- and post-capillary PH (4%)...
October 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29073911/successful-transition-from-treprostinil-to-selexipag-in-patient-with-severe-pulmonary-arterial-hypertension
#20
Asuka Furukawa, Yuichi Tamura, Hiroya Iwahori, Masato Goto, Narutaka Ohashi, Teruo Okabe, Akio Kawamura
BACKGROUND: In this report, we describe the first successful case of transition from subcutaneous administration of treprostinil to selexipag in a patient with severe pulmonary arterial hypertension (PAH), by evaluating hemodynamic changes and exercise tolerance. CASE PRESENTATION: A 38-year-old female with idiopathic PAH (IPAH) had received initial triple combination therapy (macitentan PO, tadalafil PO, and treprostinil SC) and achieved excellent improvement in hemodynamics...
October 26, 2017: BMC Pulmonary Medicine
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