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Riociguat

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https://www.readbyqxmd.com/read/29099661/express-first-in-child-use-of-the-oral-soluble-guanylate-cyclase-stimulator-riociguat-in-pulmonary-arterial-hypertension
#1
Till Spreemann, Harald Bertram, Christoph Happel, Rainer Kozlik-Feldmann, Georg Hansmann
No abstract text is available yet for this article.
January 1, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/29051185/cgmp-elevating-compounds-and-ischemic-conditioning-provide-cardioprotection-against-ischemia-and-reperfusion-injury-via-cardiomyocyte-specific-bk-channels
#2
Sandra Frankenreiter, Piotr Bednarczyk, Angelina Kniess, Nadja Bork, Julia Straubinger, Piotr Koprowski, Antoni Wrzosek, Eva Mohr, Angela Logan, Michael P Murphy, Meinrad Gawaz, Thomas Krieg, Adam Szewczyk, Viacheslav O Nikolaev, Peter Ruth, Robert Lukowski
Background -The nitric oxide-sensitive guanylyl cyclase (NO-GC)/cyclic guanosine-3',5'-monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI)-signaling pathway can afford protection against the ischemia and reperfusion (I/R) injury that occurs during myocardial infarction (MI). Reportedly, voltage and Ca(2+)-activated K(+) channels of the BK-type are stimulated by cGMP/cGKI and recent ex-vivo studies implicated that increased BK activity favors the survival of the myocardium at I/R. It remains unclear, however, whether the molecular events downstream of cGMP involve BK channels present in cardiomyocytes (CMs) or in other cardiac cell types...
October 19, 2017: Circulation
https://www.readbyqxmd.com/read/28980994/comparison-of-the-crystal-structures-and-thermochemistry-of-a-novel-soluble-guanylate-cyclase-stimulator-riociguat-and-its-solvates
#3
Xinbo Zhou, Xiurong Hu, Jianming Gu, Jianrong Zhu
Riociguat (Rio) is the first oral soluble guanylate cyclase stimulator to be approved for pulmonary arterial hypertension. In this study, form (II) of riociguat and three solvates with acetonitrile [form (III)], N,N-dimethylformamide [form (IV)] and ethyl acetate [form (V)] were crystallized. They were identified and characterized by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and their crystal structures were determined by single-crystal X-ray diffraction. No crystal structure has previously been reported for the known form (II) of riociguat...
October 1, 2017: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
https://www.readbyqxmd.com/read/28914189/a-hopeful-prospect-of-riociguat-as-a-soluble-guanylate-cyclase-stimulator-for-management-of-pressure-ulcers
#4
Soha Azadi, Hajar Ashrafi, Amir Azadi
Pressure ulcer remains as a common problem, especially developed in disabled patients and hence, subjected to continuous pressure for prolonged periods of time. Most of the studies investigating the preventive and therapeutic approaches have focused on wound cleansing, dressing and supportive strategies , as well as pharmacological therapy including zinc sulphate, vitamin A or phenytoin. Despite such efforts, pressure ulcer continues to impair the life quality and expectancy. Thus involving in the paradigm shift in biomedical studies, the recent ones focus on biological signaling pathways involving nitric oxide (NO)- soluble guanylatecyclase (sGC)- cyclic guanosine monophosphate (cGMP) contributing in vasodilation, reperfusion and oxygen delivery...
September 15, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28889107/respite-switching-to-riociguat-in-pulmonary-arterial-hypertension-patients-with-inadequate-response-to-phosphodiesterase-5-inhibitors
#5
Marius M Hoeper, Gérald Simonneau, Paul A Corris, Hossein-Ardeschir Ghofrani, James R Klinger, David Langleben, Robert Naeije, Pavel Jansa, Stephan Rosenkranz, Laura Scelsi, Ekkehard Grünig, Carmine Dario Vizza, MiKyung Chang, Pablo Colorado, Christian Meier, Dennis Busse, Raymond L Benza
A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients.RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165-440 m, cardiac index <3.0 L·min(-1)·m(-2) and pulmonary vascular resistance >400 dyn·s·cm(-5) underwent a 1-3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28732819/individual-dose-adjustment-of-riociguat-in-patients-with-pulmonary-arterial-hypertension-and-chronic-thromboembolic-pulmonary-hypertension
#6
REVIEW
Nicholas S Hill, Franck F Rahaghi, Namita Sood, Reiner Frey, Hossein-Ardeschir Ghofrani
Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2...
August 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28715904/considerations-for-optimal-management-of-patients-with-pulmonary-arterial-hypertension-a-multi-stakeholder-roundtable-discussion
#7
Sean M Studer, Martha Kingman, Luis Calo, H Eric Cannon, Jeffrey D Dunn, Thomas James, Sonya J Lewis, Robert J Gilkin, Janis A Pruett
A roundtable panel of national and regional managed care decision makers and providers met to discuss pulmonary arterial hypertension (PAH) and strategies for management. As a rare, complex disease with high economic costs and potentially devastating outcomes, PAH necessitates that managed care providers balance optimal care with efficient use of healthcare resources. PAH specialists are recognized by health plans as knowledgeable experts and integral partners in managing patients and resources. The diagnosis of PAH must be confirmed by a right heart catheterization...
May 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28705306/riociguat-for-patients-with-chronic-thromboembolic-pulmonary-hypertension-usefulness-of-transitioning-from-phosphodiesterase-type-5-inhibitor
#8
Keiko Yamamoto, Nobuhiro Tanabe, Rika Suda, Akane Sasaki, Akane Matsumura, Ryogo Ema, Hajime Kasai, Fumiaki Kato, Ayumi Sekine, Rintaro Nishimura, Takayuki Jujo, Toshihiko Sugiura, Ayako Shigeta, Seiichiro Sakao, Koichiro Tatsumi
BACKGROUND: Riociguat, the first approved drug for patients with chronic thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase (sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO) and increases sGC sensitivity for NO. The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown. METHODS AND RESULTS: Twenty-three patients were prospectively enrolled: 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat (transitioned group); 15 started riociguat anew (new or add-on group)...
July 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28671485/replacing-a-phosphodiesterase-5-inhibitor-with-riociguat-in-patients-with-connective-tissue-disease-associated-pulmonary-arterial-hypertension-a-case-series
#9
Amresh Raina, Raymond L Benza, Harrison W Farber
Patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-PAH-CTD) such as systemic sclerosis (SSc) have a poorer response to treatment and increased mortality compared with patients with idiopathic PAH. Current treatment options for PAH-CTD include prostanoids, phosphodiesterase type-5 inhibitors (PDE-5i), endothelin receptor antagonists, and the soluble guanylate cyclase stimulator riociguat. In this case series, we describe three patients with PAH-CTD related to limited scleroderma who were switched from a PDE-5i to riociguat due to insufficient clinical response...
July 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28652963/switching-from-sildenafil-to-riociguat-for-the-treatment-of-pah-and-inoperable-cteph-real-life-experiences
#10
Asger Andersen, Kasper Korsholm, Søren Mellemkjær, Jens Erik Nielsen-Kudsk
Riociguat is a novel soluble guanylate cyclase stimulator that is approved for the treatment of patients with pulmonary arterial hypertension (PAH) and patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA). As riociguat is a relatively new drug, experience of its use in clinical practice is limited, especially in patients who would not have met the inclusion criteria for the pivotal Phase III clinical trials, PATENT-1 and CHEST-1...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28610669/riociguat-for-pulmonary-arterial-hypertension-and-chronic-thromboembolic-pulmonary-hypertension-results-from-a-phase-ii-long-term-extension-study
#11
Michael Halank, Marius M Hoeper, Hossein-Ardeschir Ghofrani, F Joachim Meyer, Gerd Stähler, Jürgen Behr, Ralf Ewert, Monique Fletcher, Pablo Colorado, Sylvia Nikkho, Friedrich Grimminger
BACKGROUND: Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12-week Phase II trial. We present final data from the long-term extension phase of this study. METHODS: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0...
July 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28597779/phosphodiesterase-type-5-inhibitor-to-riociguat-transition-is-associated-with-hemodynamic-and-symptomatic-improvement-in-pulmonary-hypertension
#12
Ryan Davey, Raymond L Benza, Srinivas Murali, Amresh Raina
Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. We studied the clinical and hemodynamics effects of transitioning 12 pulmonary hypertension patients from Phosphodiesterase type 5 inhibitor (PDE5i) to riociguat, and demonstrated a significant increase in cardiac index, fall in pulmonary vascular resistance, and improvement in functional class with this switch. Switch from PDE5i to riociguat appeared to be safe and fairly well tolerated in most patients...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28557445/discovery-of-the-soluble-guanylate-cyclase-stimulator-vericiguat-bay-1021189-for-the-treatment-of-chronic-heart-failure
#13
Markus Follmann, Jens Ackerstaff, Gorden Redlich, Frank Wunder, Dieter Lang, Armin Kern, Peter Fey, Nils Griebenow, Walter Kroh, Eva-Maria Becker-Pelster, Axel Kretschmer, Volker Geiss, Volkhart Li, Alexander Straub, Joachim Mittendorf, Rolf Jautelat, Hartmut Schirok, Karl-Heinz Schlemmer, Klemens Lustig, Michael Gerisch, Andreas Knorr, Hanna Tinel, Thomas Mondritzki, Hubert Trübel, Peter Sandner, Johannes-Peter Stasch
The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-activity relationships and were able to decrease oxidative metabolism significantly...
June 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28513869/transition-of-intravenous-treprostinil-to-oral-therapy-in-a-patient-with-functional-class-iv-chronic-thromboembolic-pulmonary-hypertension
#14
Kristina M Thurber, Breann M Williams, Ruth E Bates, Robert P Frantz
Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary emboli fail to resolve with anticoagulation. For patients with inoperable or residual CTEPH, riociguat is currently the only therapy approved by the United States Food and Drug Administration. However, some patients with CTEPH may require therapy beyond riociguat, such as intravenous prostacyclins, which can present significant administration challenges in patients with complex comorbid conditions. We describe a 42-year-old man with T12 paraplegia complicated by CTEPH (functional class IV with substantial right ventricular dysfunction) and severe pressure ulcers...
August 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28458514/riociguat-a-soluble-guanylate-cyclase-stimulator-for-the-treatment-of-pulmonary-hypertension
#15
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/28356406/balloon-pulmonary-angioplasty-in-chronic-thromboembolic-pulmonary-hypertension
#16
REVIEW
Irene Lang, Bernhard C Meyer, Takeshi Ogo, Hiromi Matsubara, Marcin Kurzyna, Hossein-Ardeschir Ghofrani, Eckhard Mayer, Philippe Brenot
Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to result from incomplete resolution of pulmonary thromboemboli that undergo organisation into fibrous tissue within pulmonary arterial branches, filling pulmonary arterial lumina with collagenous obstructions. The treatment of choice is pulmonary endarterectomy (PEA) in CTEPH centres, which has low post-operative mortality and good long-term survival. For patients ineligible for PEA or who have recurrent or persistent pulmonary hypertension after surgery, medical treatment with riociguat is beneficial...
March 31, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28356404/medical-management-of-chronic-thromboembolic-pulmonary-hypertension
#17
REVIEW
Joanna Pepke-Zaba, Hossein-Ardeschir Ghofrani, Marius M Hoeper
Chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete resolution of acute pulmonary emboli, organised into fibrotic material that obstructs large pulmonary arteries, and distal small-vessel arteriopathy. Pulmonary endarterectomy (PEA) is the treatment of choice for eligible patients with CTEPH; in expert centres, PEA has low in-hospital mortality rates and excellent long-term survival. Supportive medical therapy consists of lifelong anticoagulation plus diuretics and oxygen, as needed...
March 31, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28289495/treatment-of-chronic-thromboembolic-pulmonary-hypertension-the-role-of-medical-therapy-and-balloon-pulmonary-angioplasty
#18
REVIEW
Timothy M Fernandes, David S Poch, William R Auger
Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially curable disease when treated with pulmonary thromboendarterectomy (PTE). However, even at experienced surgical centers, nearly one-third of patients with CTEPH will be deemed inoperable for reasons including distal disease, comorbidities, or out-of-proportion pulmonary hypertension. It is in these patients with inoperable CTEPH that pulmonary hypertension (PH)-targeted medical therapy and balloon pulmonary angioplasty have potential therapeutic value...
October 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/28190787/comparison-of-hemodynamic-parameters-in-treatment-na%C3%A3-ve-and-pre-treated-patients-with-pulmonary-arterial-hypertension-in-the-randomized-phase-iii-patent-1-study
#19
Nazzareno Galiè, Friedrich Grimminger, Ekkehard Grünig, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Anne M Keogh, David Langleben, Lewis J Rubin, Arno Fritsch, Neil Davie, Hossein-Ardeschir Ghofrani
BACKGROUND: Detailed hemodynamic data from the phase III PATENT-1 study of riociguat in patients with pulmonary arterial hypertension (PAH) were investigated. METHODS: Patients with PAH who were treatment naïve or pre-treated with endothelin receptor antagonists or non-intravenous prostanoids were randomly assigned to riociguat up to 2.5 mg 3 times a day or placebo. Hemodynamic parameters were assessed at baseline and week 12. RESULTS: Riociguat significantly decreased pulmonary vascular resistance in treatment-naïve (n = 221; least squares [LS] mean difference -266 dyne∙sec∙cm(-5) [95% confidence interval (CI) -357 to -175; p < 0...
May 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28025101/soluble-guanylate-cyclase-stimulators-increase-sensitivity-to-cisplatin-in-head-and-neck-squamous-cell-carcinoma-cells
#20
Traci R Tuttle, Vinita Takiar, Bhavna Kumar, Pawan Kumar, Nira Ben-Jonathan
Head and neck squamous cell carcinoma (HNSCC) is an aggressive and often fatal disease. Cisplatin is the most common chemotherapeutic drug in the treatment of HNSCC, but intrinsic and acquired resistance are frequent, and severe side effects occur at high doses. The second messenger cyclic GMP (cGMP) is produced by soluble guanylate cyclase (sGC). We previously reported that activation of the cGMP signaling cascade caused apoptosis in HNSCC cells, while others found that this pathway enhances cisplatin efficacy in some cell types...
March 28, 2017: Cancer Letters
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