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[PMID]:28757318
[Au] Autor:Self TH; Ellingson S
[Ad] Endereço:University of Tennessee Health Science Center, Methodist University Hospital, Memphis. Electronic address: tself@uthsc.edu.
[Ti] Título:New Treatment Option for Chronic Obstructive Pulmonary Disease: Two Long-Acting Bronchodilators in a Single Metered-Dose Inhaler.
[So] Source:Am J Med;130(11):1251-1254, 2017 Nov.
[Is] ISSN:1555-7162
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Combination long-acting inhaled bronchodilators are central to the management of patients with moderate to very severe chronic obstructive pulmonary disease. Glycopyrrolate is a long-acting muscarinic antagonist (LAMA), and formoterol fumarate is a long-acting beta agonist (LABA). In randomized controlled trials, this LAMA/LABA combination in a metered-dose inhaler was shown to be effective in improving pulmonary function and quality of life. Clinicians now have the availability of 3 delivery systems for LAMA/LABA therapy, including metered-dose inhaler, dry-powder inhaler, and Soft Mist inhaler. On the basis of numerous patient factors, such as cognitive ability, manual strength/dexterity, and peak inspiratory flow, clinicians may select the most appropriate inhalation device. For each inhalation device, persistent patient education is absolutely essential, including observation of patient use. International evidence-based guidelines stress the critical importance of ensuring correct use of inhalation devices.
[Mh] Termos MeSH primário: Agonistas de Receptores Adrenérgicos beta 2/farmacologia
Fumarato de Formoterol/farmacologia
Glicopirrolato/farmacologia
Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
[Mh] Termos MeSH secundário: Broncodilatadores/farmacologia
Preparações de Ação Retardada/farmacologia
Combinação de Medicamentos
Seres Humanos
Antagonistas Muscarínicos/farmacologia
Nebulizadores e Vaporizadores
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic beta-2 Receptor Agonists); 0 (Bronchodilator Agents); 0 (Delayed-Action Preparations); 0 (Drug Combinations); 0 (Muscarinic Antagonists); V92SO9WP2I (Glycopyrrolate); W34SHF8J2K (Formoterol Fumarate)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


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[PMID]:28596292
[Au] Autor:Kistemaker LEM; Oenema TA; Baarsma HA; Bos IST; Schmidt M; Facchinetti F; Civelli M; Villetti G; Gosens R
[Ad] Endereço:Department of Molecular Pharmacology, University of Groningen, The Netherlands; l.e.m.kistemaker@rug.nl.
[Ti] Título:The PDE4 inhibitor CHF-6001 and LAMAs inhibit bronchoconstriction-induced remodeling in lung slices.
[So] Source:Am J Physiol Lung Cell Mol Physiol;313(3):L507-L515, 2017 Sep 01.
[Is] ISSN:1522-1504
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Combination therapy of PDE4 inhibitors and anticholinergics induces bronchoprotection in COPD. Mechanical forces that arise during bronchoconstriction may contribute to airway remodeling. Therefore, we investigated the impact of PDE4 inhibitors and anticholinergics on bronchoconstriction-induced remodeling. Because of the different mechanism of action of PDE4 inhibitors and anticholinergics, we hypothesized functional interactions of these two drug classes. Guinea pig precision-cut lung slices were preincubated with the PDE4 inhibitors CHF-6001 or roflumilast and/or the anticholinergics tiotropium or glycopyorrolate, followed by stimulation with methacholine (10 µM) or TGF-ß (2 ng/ml) for 48 h. The inhibitory effects on airway smooth muscle remodeling, airway contraction, and TGF-ß release were investigated. Methacholine-induced protein expression of smooth muscle-myosin was fully inhibited by CHF-6001 (0.3-100 nM), whereas roflumilast (1 µM) had smaller effects. Tiotropium and glycopyrrolate fully inhibited methacholine-induced airway remodeling (0.1-30 nM). The combination of CHF-6001 and tiotropium or glycopyrrolate, in concentrations partially effective by themselves, fully inhibited methacholine-induced remodeling in combination. CHF-6001 did not affect airway closure and had limited effects on TGF-ß -induced remodeling, but rather, it inhibited methacholine-induced TGF-ß release. The PDE4 inhibitor CHF-6001, and to a lesser extent roflumilast, and the LAMAs tiotropium and glycopyrrolate inhibit bronchoconstriction-induced remodeling. The combination of CHF-6001 and anticholinergics was more effective than the individual compounds. This cooperativity might be explained by the distinct mechanisms of action inhibiting TGF-ß release and bronchoconstriction.
[Mh] Termos MeSH primário: Remodelação das Vias Aéreas/efeitos dos fármacos
Broncoconstrição/efeitos dos fármacos
Antagonistas Colinérgicos/farmacologia
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo
Pulmão/efeitos dos fármacos
Pulmão/fisiopatologia
Inibidores da Fosfodiesterase 4/farmacologia
Sulfonamidas/farmacologia
para-Aminobenzoatos/farmacologia
[Mh] Termos MeSH secundário: Aminopiridinas
Animais
Benzamidas
Ciclopropanos
Interações Medicamentosas
Glicopirrolato/farmacologia
Cobaias
Masculino
Cloreto de Metacolina/farmacologia
Brometo de Tiotrópio/farmacologia
Fator de Crescimento Transformador beta/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide); 0 (Aminopyridines); 0 (Benzamides); 0 (Cholinergic Antagonists); 0 (Cyclopropanes); 0 (Phosphodiesterase 4 Inhibitors); 0 (Sulfonamides); 0 (Transforming Growth Factor beta); 0 (para-Aminobenzoates); 0P6C6ZOP5U (Roflumilast); 0W5ETF9M2K (Methacholine Chloride); EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4); V92SO9WP2I (Glycopyrrolate); XX112XZP0J (Tiotropium Bromide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE
[do] DOI:10.1152/ajplung.00069.2017


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[PMID]:28443352
[Au] Autor:Rabe KF
[Ad] Endereço:a LungenClinic Grosshansdorf, Airway Research Center North , Member of the German Center for Lung Research (DZL) , Grosshansdorf , Germany.
[Ti] Título:GFF MDI for the improvement of lung function in COPD - A look at the PINNACLE-1 and PINNACLE-2 data and beyond.
[So] Source:Expert Rev Clin Pharmacol;10(7):685-698, 2017 Jul.
[Is] ISSN:1751-2441
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and incidence rates are continuing to rise. Long-acting bronchodilators are the foundation on which current pharmacological approaches to COPD management are built, with long-acting muscarinic antagonists (LAMAs) and long-acting ß -agonists (LABAs) recommended across the spectrum of the disease continuum. Combining LAMAs and LABAs provides additional lung function improvements and relief of patient symptoms compared with either therapy alone. Several options for LAMA/LABA fixed-dose combinations (FDC) delivered via a single inhaler device are available; however, only recently has a LAMA/LABA FDC become available as a pressurized metered dose inhaler (MDI). Areas covered: This article describes the rationale for the development of the LAMA/LABA FDC of glycopyrrolate and formoterol fumarate, formulated by Co-Suspension™ Delivery Technology and delivered by MDI (GFF MDI). The clinical trial program of GFF MDI, including the pivotal Phase III studies (PINNACLE-1 and PINNACLE-2) that supported regulatory approval, are reviewed, providing insights into interpretation and future directions for research. Expert commentary: LAMA/LABA FDCs are already a crucial part of the COPD treatment paradigm, but additional data are needed in order to maximize their role as maintenance therapies in patients with COPD.
[Mh] Termos MeSH primário: Broncodilatadores/administração & dosagem
Fumarato de Formoterol/administração & dosagem
Glicopirrolato/administração & dosagem
Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração por Inalação
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem
Agonistas de Receptores Adrenérgicos beta 2/farmacologia
Broncodilatadores/farmacologia
Preparações de Ação Retardada
Combinação de Medicamentos
Sistemas de Liberação de Medicamentos
Fumarato de Formoterol/farmacologia
Glicopirrolato/farmacologia
Seres Humanos
Inaladores Dosimetrados
Antagonistas Muscarínicos/administração & dosagem
Antagonistas Muscarínicos/farmacologia
Doença Pulmonar Obstrutiva Crônica/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-2 Receptor Agonists); 0 (Bronchodilator Agents); 0 (Delayed-Action Preparations); 0 (Drug Combinations); 0 (Muscarinic Antagonists); V92SO9WP2I (Glycopyrrolate); W34SHF8J2K (Formoterol Fumarate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE
[do] DOI:10.1080/17512433.2017.1320218


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[PMID]:28183573
[Au] Autor:Howard J; Wigley J; Rosen G; D'mello J
[Ad] Endereço:Resident- Mount Sinai Medical Center of Florida, Miami Beach, FL.
[Ti] Título:Glycopyrrolate: It's time to review.
[So] Source:J Clin Anesth;36:51-53, 2017 Feb.
[Is] ISSN:1873-4529
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Medication shortages have become an all-too-common inconvenience that has forced anesthesia providers to examine our administering practices. Because of these shortages, commonly used medications are at the greatest risk. Glycopyrrolate (Robinul), which has been in short supply in recent years, is one of the most widely used anticholinergic agents, especially in conjunction with the anticholinesterase neostigmine, for reversal of neuromuscular blockade (NMB) drugs. Here we review multiple studies from 1972 through 1986 that used varying methods of patient selection and dosage and drug combination criteria, and which noted that glycopyrrolate had a superior efficacy and adverse effect profile when compared with atropine in NMB reversal. Meta-analysis from these studies indicated that the dosage of 0.2 mg of glycopyrrolate for every 1 mg of neostigmine, given concomitantly (maximum 1 mg glycopyrrolate and 5 mg neostigmine), demonstrated the greatest efficacy with the lowest incidence of unwanted adverse effects. It has now become common practice to use a dosage ratio of 0.2 mg glycopyrrolate to 1.0 mg neostigmine for NMB reversal. Yet since 1986, there have been no studies on reversal with glycopyrrolate and neostigmine. Frequent medication shortages and good medical practice should be an impetus for clinicians to reevaluate dosing practices of critical medications and revisit these drugs, such as glycopyrrolate, with more current studies.
[Mh] Termos MeSH primário: Glicopirrolato/administração & dosagem
[Mh] Termos MeSH secundário: Pesquisa Biomédica
Relação Dose-Resposta a Droga
Esquema de Medicação
Glicopirrolato/provisão & distribuição
Seres Humanos
Antagonistas Muscarínicos/administração & dosagem
Antagonistas Muscarínicos/provisão & distribuição
Neostigmina/administração & dosagem
Bloqueio Neuromuscular/métodos
Bloqueadores Neuromusculares/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Muscarinic Antagonists); 0 (Neuromuscular Blocking Agents); 3982TWQ96G (Neostigmine); V92SO9WP2I (Glycopyrrolate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE


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[PMID]:28176893
[Au] Autor:Wedzicha JA; Zhong N; Ichinose M; Humphries M; Fogel R; Thach C; Patalano F; Banerji D
[Ad] Endereço:National Heart and Lung Institute, Imperial College London, London, UK.
[Ti] Título:Indacaterol/glycopyrronium versus salmeterol/fluticasone in Asian patients with COPD at a high risk of exacerbations: results from the FLAME study.
[So] Source:Int J Chron Obstruct Pulmon Dis;12:339-349, 2017.
[Is] ISSN:1178-2005
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting ß -agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study. PATIENTS AND METHODS: Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included. IND/GLY was compared versus SFC for effects on exacerbations, lung function (forced expiratory volume in 1 second [FEV ] and forced vital capacity [FVC]), health status (St George's Respiratory Questionnaire [SGRQ]), rescue medication use, and safety. RESULTS: A total of 510 Asian patients (IND/GLY, n=250 or SFC, n=260) were included. Compared to the overall FLAME population, the Asian cohort had more males, a shorter duration of COPD, fewer patients using inhaled corticosteroid (ICS) at screening, fewer current smokers, and more patients with very severe COPD. IND/GLY significantly reduced the rate of moderate/severe exacerbations (rate ratio: 0.75; 95% confidence interval: 0.58-0.97; =0.027) and prolonged time to first moderate/severe exacerbation versus SFC (hazard ratio: 0.77; 95% confidence interval: 0.59-1.01; =0.055). Predose trough FEV and FVC significantly improved in Asian patients ( <0.001). IND/GLY improved SGRQ for COPD (SGRQ-C score; =0.006) and reduced rescue medication use ( =0.058) at week 52. Pneumonia incidence was 3.6% with IND/GLY and 7.7% with SFC ( =0.046). CONCLUSION: In exacerbating Asian COPD patients, IND/GLY was more effective than SFC.
[Mh] Termos MeSH primário: Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem
Grupo com Ancestrais do Continente Asiático
Broncodilatadores/administração & dosagem
Combinação Fluticasona-Salmeterol/administração & dosagem
Glicopirrolato/administração & dosagem
Indanos/administração & dosagem
Pulmão/efeitos dos fármacos
Antagonistas Muscarínicos/administração & dosagem
Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
Quinolonas/administração & dosagem
[Mh] Termos MeSH secundário: Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos
Idoso
Ásia/epidemiologia
Broncodilatadores/efeitos adversos
Progressão da Doença
Método Duplo-Cego
Feminino
Combinação Fluticasona-Salmeterol/efeitos adversos
Volume Expiratório Forçado
Glicopirrolato/efeitos adversos
Nível de Saúde
Seres Humanos
Indanos/efeitos adversos
Pulmão/fisiopatologia
Masculino
Meia-Idade
Antagonistas Muscarínicos/efeitos adversos
Doença Pulmonar Obstrutiva Crônica/diagnóstico
Doença Pulmonar Obstrutiva Crônica/etnologia
Doença Pulmonar Obstrutiva Crônica/fisiopatologia
Quinolonas/efeitos adversos
Recuperação de Função Fisiológica
Inquéritos e Questionários
Fatores de Tempo
Resultado do Tratamento
Capacidade Vital
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adrenergic beta-2 Receptor Agonists); 0 (Bronchodilator Agents); 0 (Fluticasone-Salmeterol Drug Combination); 0 (Indans); 0 (Muscarinic Antagonists); 0 (Quinolones); 8OR09251MQ (indacaterol); V92SO9WP2I (Glycopyrrolate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.2147/COPD.S125058


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[PMID]:28129312
[Au] Autor:Man WH; Colen-de Koning JC; Schulte PF; Cahn W; van Haelst IM; Doodeman HJ; Egberts TC; Heerdink ER; Wilting I
[Ad] Endereço:From the *Department of Clinical Pharmacy, University Medical Center Utrecht; †Department of Clinical Pharmacy, Medical Centrum Alkmaar; ‡Mental Health Services North-Holland North, Heerhugowaard; §Department of Psychiatry, University Medical Center Utrecht; and ∥Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
[Ti] Título:The Effect of Glycopyrrolate on Nocturnal Sialorrhea in Patients Using Clozapine: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial.
[So] Source:J Clin Psychopharmacol;37(2):155-161, 2017 Apr.
[Is] ISSN:1533-712X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nocturnal sialorrhea is one of the most frequent adverse events in clozapine treatment. Symptomatic management of sialorrhea usually consists of off-label treatment with anticholinergic agents. The aim of the current study is to evaluate the efficacy and safety of glycopyrrolate in patients using clozapine that experience sialorrhea. METHODS: In a double-blind randomized crossover trial, patients with nocturnal sialorrhea (n = 32) were randomized to treatment with glycopyrrolate 1 mg or placebo. This double-blinded phase was followed by an optional open label extension phase with glycopyrrolate 2 mg. Exposure periods consisted of 6 consecutive days and were separated with 1 washout week. The primary outcome was clinical improvement of nocturnal sialorrhea assessed by the Patient Global Impression of Improvement (PGI-I). RESULTS: The proportion of patients with a clinical improvement according to PGI-I did not significantly differ between 1 mg and placebo (18.8% vs 6.3%, P = 0.289); however, in patients using glycopyrrolate 2 mg once daily versus placebo, it did (43.5% vs 6.3%, P = 0.039). Glycopyrrolate was not associated with severe adverse events or worsening of cognitive adverse events. CONCLUSIONS: Glycopyrrolate 1 mg was not superior to placebo, whereas 2 mg showed a significant clinical improvement of nocturnal sialorrhea compared with placebo. Glycopyrrolate seemed to be a tolerable anticholinergic agent in the treatment of clozapine-associated sialorrhea.
[Mh] Termos MeSH primário: Antipsicóticos/efeitos adversos
Clozapina/administração & dosagem
Glicopirrolato/farmacologia
Antagonistas Muscarínicos/farmacologia
Avaliação de Resultados (Cuidados de Saúde)
Sialorreia/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Estudos Cross-Over
Método Duplo-Cego
Feminino
Glicopirrolato/administração & dosagem
Seres Humanos
Masculino
Transtornos Mentais/tratamento farmacológico
Meia-Idade
Antagonistas Muscarínicos/administração & dosagem
Sialorreia/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Muscarinic Antagonists); J60AR2IKIC (Clozapine); V92SO9WP2I (Glycopyrrolate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE
[do] DOI:10.1097/JCP.0000000000000657


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[PMID]:28081026
[Au] Autor:Lee ZI; Yu KJ; Lee DH; Hong SK; Woo SB; Kim JM; Park D
[Ad] Endereço:From the Department of Rehabilitation Medicine, Daegu Fatima Hospital, Daegu, South Korea.
[Ti] Título:The Effect of Nebulized Glycopyrrolate on Posterior Drooling in Patients with Brain Injury: Two Cases of Different Brain Lesions.
[So] Source:Am J Phys Med Rehabil;96(8):e155-e158, 2017 Aug.
[Is] ISSN:1537-7385
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Posterior drooling, which can lead to substantial respiratory morbidity, including unexplained lung diseases and recurrent pneumonia, is an important issue in the rehabilitation unit. There are various treatment options for posterior drooling, including pharmacologic therapy, oral motor or behavioral therapy, biofeedback, local glandular injection of botulinum toxin, irradiation, and surgery. Among them, nebulized glycopyrrolate has the following advantages: It is noninvasive and is relatively free of central adverse effects because it does not cross the blood-brain barrier unlike other anticholinergics. Although there has been one case report regarding the effectiveness of nebulized glycopyrrolate for drooling in a motor neuron patient, there have not been any reports on its effectiveness for posterior drooling. Herein, we report two cases (an 82-year-old male bilateral hemiplegic stroke patient and a 1-year-old female cerebral palsy infant with bilaterally spastic hemiplegia of posterior drooling treated with nebulized glycopyrrolate) and identify salivary aspiration and the effect of nebulized glycopyrrolate using radionuclide salivagram. Considering its advantages and effectiveness, nebulized glycopyrrolate should be considered as one of the reliable methods to manage posterior drooling in patients with impaired cognition or swallowing difficulties, such as severe brain injury.
[Mh] Termos MeSH primário: Paralisia Cerebral/complicações
Glicopirrolato/administração & dosagem
Antagonistas Muscarínicos/administração & dosagem
Sialorreia/tratamento farmacológico
Acidente Vascular Cerebral/complicações
[Mh] Termos MeSH secundário: Administração por Inalação
Idoso de 80 Anos ou mais
Feminino
Hemiplegia/complicações
Seres Humanos
Lactente
Masculino
Nebulizadores e Vaporizadores
Glândulas Salivares/efeitos dos fármacos
Sialorreia/etiologia
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Muscarinic Antagonists); V92SO9WP2I (Glycopyrrolate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170113
[St] Status:MEDLINE
[do] DOI:10.1097/PHM.0000000000000669


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[PMID]:27966225
[Au] Autor:Siebenmann C; Rasmussen P; Hug M; Keiser S; Flück D; Fisher JP; Hilty MP; Maggiorini M; Lundby C
[Ad] Endereço:Centre for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zürich, Switzerland.
[Ti] Título:Parasympathetic withdrawal increases heart rate after 2 weeks at 3454 m altitude.
[So] Source:J Physiol;595(5):1619-1626, 2017 Mar 01.
[Is] ISSN:1469-7793
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:KEY POINTS: Heart rate is increased in chronic hypoxia and we tested whether this is the result of increased sympathetic nervous activity, reduced parasympathetic nervous activity, or a non-autonomic mechanism. In seven lowlanders, heart rate was measured at sea level and after 2 weeks at high altitude after individual and combined pharmacological inhibition of sympathetic and/or parasympathetic control of the heart. Inhibition of parasympathetic control of the heart alone or in combination with inhibition of sympathetic control abolished the high altitude-induced increase in heart rate. Inhibition of sympathetic control of the heart alone did not prevent the high altitude-induced increase in heart rate. These results indicate that a reduced parasympathetic nervous activity is the main mechanism underlying the elevated heart rate in chronic hypoxia. ABSTRACT: Chronic hypoxia increases resting heart rate (HR), but the underlying mechanism remains incompletely understood. We investigated the relative contributions of the sympathetic and parasympathetic nervous systems, along with potential non-autonomic mechanisms, by individual and combined pharmacological inhibition of muscarinic and/or ß-adrenergic receptors. In seven healthy lowlanders, resting HR was determined at sea level (SL) and after 15-18 days of exposure to 3454 m high altitude (HA) without drug intervention (control, CONT) as well as after intravenous administration of either propranolol (PROP), or glycopyrrolate (GLYC), or PROP and GLYC in combination (PROP+GLYC). Circulating noradrenaline concentration increased from 0.9 ± 0.4 nmol l at SL to 2.7 ± 1.5 nmol l at HA (P = 0.03). The effect of HA on HR depended on the type of autonomic inhibition (P = 0.006). Specifically, HR was increased at HA from 64 ± 10 to 74 ± 12 beats min during the CONT treatment (P = 0.007) and from 52 ± 4 to 59 ± 5 beats min during the PROP treatment (P < 0.001). In contrast, HR was similar between SL and HA during the GLYC treatment (110 ± 7 and 112 ± 5 beats min , P = 0.28) and PROP+GLYC treatment (83 ± 5 and 85 ± 5 beats min , P = 0.25). Our results identify a reduction in cardiac parasympathetic activity as the primary mechanism underlying the elevated HR associated with 2 weeks of exposure to hypoxia. Unexpectedly, the sympathoactivation at HA that was evidenced by increased circulating noradrenaline concentration had little effect on HR, potentially reflecting down-regulation of cardiac ß-adrenergic receptor function in chronic hypoxia. These effects of chronic hypoxia on autonomic control of the heart may concern not only HA dwellers, but also patients with disorders that are associated with hypoxaemia.
[Mh] Termos MeSH primário: Altitude
Hemodinâmica
Sistema Nervoso Parassimpático/fisiologia
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos beta/farmacologia
Adulto
Glicopirrolato/farmacologia
Hemodinâmica/efeitos dos fármacos
Seres Humanos
Hipóxia/sangue
Hipóxia/fisiopatologia
Masculino
Antagonistas Muscarínicos/farmacologia
Norepinefrina/sangue
Propranolol/farmacologia
Adulto Jovem
[Pt] Tipo de publicação:CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Muscarinic Antagonists); 9Y8NXQ24VQ (Propranolol); V92SO9WP2I (Glycopyrrolate); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161215
[St] Status:MEDLINE
[do] DOI:10.1113/JP273726


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[PMID]:27940287
[Au] Autor:Watz H; Mailänder C; May C; Baier M; Kirsten AM
[Ad] Endereço:Pulmonary Research Institute at Lung Clinic Grosshansdorf GmbH, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. Electronic address: h.watz@pulmoresearch.de.
[Ti] Título:Fast onset of action of glycopyrronium compared with tiotropium in patients with moderate to severe COPD - A randomised, multicentre, crossover trial.
[So] Source:Pulm Pharmacol Ther;42:13-20, 2017 Feb.
[Is] ISSN:1522-9629
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Long-acting bronchodilators, including anticholinergics glycopyrronium and tiotropium, are central to symptomatic management of chronic obstructive pulmonary disease (COPD). In patients with moderate to severe COPD, glycopyrronium has demonstrated comparable efficacy to open-label and single-blinded tiotropium, but with faster onset of bronchodilation. The FAST study assessed the efficacy of glycopyrronium compared with tiotropium in serial spirometry and body plethysmography assessments to further characterize the earlier onset of action associated with glycopyrronium. METHODS: In this German multicentre, randomised, double-blinded, double-dummy, cross-over study, patients with moderate-to-severe COPD received single-dose of glycopyrronium 44 µg and tiotropium 18 µg via the Breezhaler and Handihaler devices, respectively. Primary objective was to demonstrate superiority of glycopyrronium over tiotropium in terms of improvement in forced expiratory volume in 1 s as assessed by the area under the curve from 0 to 2 h (FEV AUC ). Secondary endpoints were functional residual capacity (FRC), residual volume (RV), inspiratory capacity (IC), and specific airway resistance (sR ), all measured by body plethysmography. RESULTS: Of the 152 patients randomised, 99.3% completed the study. After inhalation of the single dose, glycopyrronium demonstrated superiority over tiotropium in early bronchodilation as assessed by improvement in FEV AUC (least squares mean treatment difference = 37 mL; 95% CI: 16, 59 mL; p < 0.01) and FEV at 15 min post-dose (least square mean treatment difference = 36 mL; 95% CI: 14, 58 mL; p < 0.01). Both treatments showed similar improvements in FRC , RV, and IC. Glycopyrronium showed statistically significant improvement in sR compared with tiotropium over the first 90 min after dosing, with the difference of 0.184 kPa × s at 90 min post-dose (95% CI: 0.315,0.054 kPa × s; p < 0.01). CONCLUSIONS: Glycopyrronium was superior to tiotropium in terms of early bronchodilation. Although both glycopyrronium and tiotropium showed similar improvements in static lung volume parameters, glycopyrronium reduced specific airway resistance faster than tiotropium, which could in part explain the earlier FEV response seen with glycopyrronium. TRIAL REGISTRATION: ClinicalTrials.govNCT01922271.
[Mh] Termos MeSH primário: Broncodilatadores/uso terapêutico
Glicopirrolato/uso terapêutico
Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
Brometo de Tiotrópio/uso terapêutico
[Mh] Termos MeSH secundário: Administração por Inalação
Idoso
Broncodilatadores/administração & dosagem
Estudos Cross-Over
Método Duplo-Cego
Feminino
Volume Expiratório Forçado
Alemanha
Glicopirrolato/administração & dosagem
Seres Humanos
Capacidade Inspiratória
Masculino
Meia-Idade
Pletismografia Total
Doença Pulmonar Obstrutiva Crônica/fisiopatologia
Volume Residual
Índice de Gravidade de Doença
Espirometria
Fatores de Tempo
Brometo de Tiotrópio/administração & dosagem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Bronchodilator Agents); V92SO9WP2I (Glycopyrrolate); XX112XZP0J (Tiotropium Bromide)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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[PMID]:27939204
[Au] Autor:Vaghela MM; Mahajan JK; Sundram J; Bhardwaj N; Rao KL
[Ad] Endereço:Department of Pediatric Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
[Ti] Título:Role of glycopyrrolate in healing of anastomotic dehiscence after primary repair of esophageal atresia in a low resource setting-A randomized controlled study.
[So] Source:J Pediatr Surg;52(3):420-423, 2017 Mar.
[Is] ISSN:1531-5037
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: To investigate the role of glycopyrrolate in decreasing oral secretions in patients of esophageal atresia (EA) with anastomotic leak and evaluate its effect on healing of anastomotic dehiscence. METHODS: The study comprised consecutive neonates of esophageal atresia, who had undergone primary surgery and developed anastomotic leak. The patients were randomized into two groups with the observer blinded to the group. The patients in the treatment group were administered glycopyrrolate in the dose of 8 µg/kg 8 hourly, whereas placebo group patients were injected normal saline only. Neonates, in both the groups, were managed conservatively based on the clinical and radiological parameters. The end points of the study were either resolution or progression of the leak. The study was approved by the institute ethics committee. RESULTS: There were 21 patients each in two groups with comparable preoperative characteristics. All the cases had anastomotic leaks clinically detectable in the chest tube. Saliva alone constituted the leak material in 18 cases in the treatment group and 10 in the placebo group. Cumulative total of mean chest tube output per patient for all patients in the treatment group was 124.15ml as compared to 370.27ml in the placebo group (p=0.001). Anastomotic leak stopped in 16 cases (76%) in the treatment group, as compared to 6 cases (29%) in the placebo group (p=0.004). The postoperative ventilation was required in 8 cases (8/21, 38%) in the treatment group and 17 cases (17/21, 81%) in the placebo group (p=0.010). In the treatment group, the diversion procedures were carried out in 2 out of 21 cases (10%), whereas in the placebo group, 52% of the patients (11/21) required such an intervention (p=0.003). At the time of discharge, the oral feeds could be started in 15 cases (15/21, 71%) in the treatment group, as compared to 3 (3/21, 14%) in the placebo group (p=0.0004). CONCLUSIONS: Administration of glycopyrrolate in patients of anastomotic leak after primary repair of esophageal atresia resulted in reduced oral secretions, which helped in healing of the anastomotic dehiscence in a significant number of patients.
[Mh] Termos MeSH primário: Fístula Anastomótica/tratamento farmacológico
Atresia Esofágica/cirurgia
Glicopirrolato/administração & dosagem
Antagonistas Muscarínicos/administração & dosagem
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Fístula Anastomótica/etiologia
Fístula Anastomótica/cirurgia
Atresia Esofágica/diagnóstico por imagem
Feminino
Seres Humanos
Índia
Recém-Nascido
Masculino
Estudos Prospectivos
Radiografia
Método Simples-Cego
Deiscência da Ferida Operatória/tratamento farmacológico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Muscarinic Antagonists); V92SO9WP2I (Glycopyrrolate)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170426
[Lr] Data última revisão:
170426
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE



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