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1.
Expert Rev Clin Pharmacol ; 13(2): 103-113, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31951778

RESUMO

Introduction: Treatment options for COPD have evolved rapidly in the last decade and inhaled bronchodilators have largely supplanted the use of oral bronchodilators because of their increased efficacy and excellent safety with topical delivery to the lung. Recently added to the therapeutic armamentarium are fixed-dose combinations (FDC) of two long acting bronchodilators. LAMAs (long acting muscarinic antagonists) and LABAs (long acting beta agonists) are the main classes available and use different pathways to effectively produce bronchial smooth muscle relaxation.Areas covered: The most recent inhaled FDC LAMA/LABA to come to market is Aclidinium Bromide and Formoterol Fumarate. We searched databases of PubMed, Cochrane Library, and manufacturers' websites and retrieved all the randomized-controlled trials (RCTs) conducted with these drugs up to September 2019.Expert opinion: It is likely that FDCs will become the core of our COPD pharmacotherapy for all but the mildest COPD patients. These individual drugs have excellent efficacy and safety records for the maintenance treatment of COPD. Studies have demonstrated that twice daily treatment with aclidinium/formoterol resulted in significant improvement in lung function and an improved exercise tolerance when compared to placebo. Adverse effects are within the range of what is seen with other LAMA/LABA combinations.


Assuntos
Fumarato de Formoterol/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Broncodilatadores/farmacologia , Combinação de Medicamentos , Fumarato de Formoterol/efeitos adversos , Fumarato de Formoterol/farmacologia , Humanos , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tropanos/efeitos adversos , Tropanos/farmacologia
2.
Expert Opin Drug Metab Toxicol ; 16(2): 103-110, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918590

RESUMO

Introduction: Overactive bladder (OAB) has a heterogeneous presentation that varies between individuals and by gender. Treatment with antimuscarinic medications is standard first line pharmacotherapy for most patients with OAB. However, gender specific differences in the pharmacokinetics and pharmacodynamics of antimuscarinic therapy are often overlooked and not discussed.Areas covered: This review will explore differences by gender between the presentation and treatment of OAB. We will discuss the differences between sexes in terms of lower urinary tract anatomy, muscarinic receptors, and hormone variation. The effect of antimuscarinics on males and females as well as adherence and persistence patterns will be reviewed in order to fully review all available literature on the gender specific pharmacokinetic and pharmacodynamic considerations for antimuscarinic use in the treatment of OAB.Expert opinion: Despite extensive research into various antimuscarinic formulations and therapeutic regimens for the treatment of OAB, identification of gender specific pharmacokinetic and pharmacodynamics considerations remains scant. As our knowledge and understanding of OAB, muscarinic receptors, and antimuscarinic medications evolve, we will hopefully be better able to understand and implement gender-specific and genomic-sprecific treatment regimens and considerations for improved clinical outcomes.


Assuntos
Antagonistas Muscarínicos/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Animais , Feminino , Humanos , Masculino , Adesão à Medicação , Antagonistas Muscarínicos/farmacocinética , Antagonistas Muscarínicos/farmacologia , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/metabolismo , Fatores Sexuais , Bexiga Urinária Hiperativa/fisiopatologia
3.
Expert Opin Drug Metab Toxicol ; 16(2): 143-148, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958237

RESUMO

Introduction: There is solid evidence that in patients with poorly controlled severe asthma despite the use of ICS and LABA, the addition of LAMAs, such as tiotropium, significantly increases the time to the first severe exacerbation and provides a modest but sustained bronchodilation. However, only a very limited number of pharmacokinetic studies with these agents have been performed in asthmatic patients.Areas covered: The pharmacokinetic profile of inhaled tiotropium, umeclidinium and glycopyrronium in healthy volunteers and that of inhaled tiotropium and umeclidinium in asthmatic patients have been reviewed.Expert opinion: In asthmatic patients, LAMAs are rapidly absorbed into the systemic compartment and demonstrate bi-exponential elimination (rapidly declining plasma concentrations followed by slow apparent terminal elimination). Apparently, the severity of asthma does not change the pharmacokinetics of LAMAs. The limited information available is focused on the plasma pharmacokinetic profile of these drugs and, consequently, although suitable for establishing a systemic safety profile, it does not tell us much about possible therapeutic efficacy of LAMAs in asthmatics because quantification of systemic plasma values is neither at the airways, which are their site of action nor representative of their transport to this site.


Assuntos
Asma/tratamento farmacológico , Antagonistas Muscarínicos/administração & dosagem , Receptor Muscarínico M3/antagonistas & inibidores , Administração por Inalação , Antiasmáticos/administração & dosagem , Antiasmáticos/farmacocinética , Antiasmáticos/farmacologia , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Broncodilatadores/farmacocinética , Broncodilatadores/farmacologia , Humanos , Antagonistas Muscarínicos/farmacocinética , Antagonistas Muscarínicos/farmacologia , Receptor Muscarínico M3/metabolismo , Índice de Gravidade de Doença
6.
Am J Case Rep ; 20: 1418-1421, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31554781

RESUMO

BACKGROUND Pyridostigmine is a quaternary amine parasympathomymetic which inhibits acetylcholinesterase for the treatment of various conditions such as myasthenia gravis. Previously, no cases of pyridostigmine toxicity in human beings have been reported except the cases reported among the troops of Persian Gulf War. CASE REPORT A 47-year-old female intentionally ingested a high dose of pyridostigmine (Mestinon) and developed its toxic symptoms within 1 hour of ingestion. She was treated with injections of atropine and pralidoxime. The patient made an excellent recovery and responded to the classical treatment using atropine and pralidoxime. She was discharged on the second day of admission. CONCLUSIONS The authors demonstrated that pyridostigmine poisoning is self-limiting and well tolerated by young adults; however, unwanted effects of pyridostigmine on the heart has still to be considered which may become profound to the point of generating heart failure, syncope, or stress particularly in elderly patients. As the literature on human toxicity with pyridostigmine is scarce, not much data is available on its toxicity. However, prompt and specific management of pyridostigmine toxicity promises safety.


Assuntos
Inibidores da Colinesterase/efeitos adversos , Miastenia Gravis , Brometo de Piridostigmina/efeitos adversos , Tentativa de Suicídio , Atropina/administração & dosagem , Reativadores da Colinesterase/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Miastenia Gravis/tratamento farmacológico , Compostos de Pralidoxima/administração & dosagem
7.
Int J Neurosci ; 129(12): 1203-1212, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31393204

RESUMO

Purpose of the study: Kaempferol (KM) is a flavonoid found in plant-derived foods and medicinal plants. Recently, it is well established that KM plays a protective role to develop Alzheimer's disease. The current study aimed at evaluating the effect of intracerebroventricular micro-injection of KM on memory retention of passive avoidance learning (MRPAM) and identifying the potentially related cholinergic mechanisms (ChMs) in rats. Materials and methods: In the current study, male Wistar rats randomly divided into control, vehicle and KM (10, 20 and 40 µg/rat) groups. Moreover, MRPAM was evaluated by shuttle box test. The role of ChM was studied using non-selective and selective acetylcholine antagonists (scopolamine [SCN], 4-DAMP and methoctramine [MN], respectively) as well as pirenzepine (PZ) in combination with KM. Results: The employment of KM (40 µg/rat) improved the SCN-induced memory impairment in MRPAM. Co-treatment with KM (40 µg/rat) plus 4-DAMP significantly increased the step-through latency (STL, P < 0.05; 167 ± 28 s) and decreased the total dark chamber (TDC, P < 0.05; 121 ± 31 s) compared with those of the 4-DAMP group (STL: 75 ± 13 s; TDC: 178 ± 46 s). Co-treatment with KM (40 µg/rat) plus PZ attenuated STL, and also increased TDC (P < 0.01; 220 ± 28 s) compared with those of the PZ group. Co-treatment with KM (10 and 20 µg/rat) and MN increased STL (P < 0.05), and deceased TDC compared with those of the MN group (P < 0.01). Conclusions: Totally, the results of the present study showed that cholinergic system may be involved in improving effect of KM on SCN-induced memory impairment.


Assuntos
Acetilcolina/fisiologia , Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas Colinérgicos/administração & dosagem , Quempferóis/administração & dosagem , Memória/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Animais , Aprendizagem da Esquiva/fisiologia , Diaminas/administração & dosagem , Injeções Intraventriculares , Masculino , Memória/fisiologia , Microinjeções , Piperidinas/administração & dosagem , Pirenzepina/administração & dosagem , Ratos Wistar , Escopolamina/administração & dosagem
8.
Int J Chron Obstruct Pulmon Dis ; 14: 1539-1548, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371939

RESUMO

Background: This study aims to compare the effects of single inhaler triple therapy comprised of inhaled corticosteroids (ICSs), long-acting ß2-agonists (LABAs), and long-acting muscarinic receptor antagonists (LAMAs) with dual therapies comprised of either LABA/LAMA, ICS/LABA or separate ICS/LABA plus LAMA triple therapy. Methods: The Pubmed, Embase, and Cochrane databases were searched up to October 31st 2018. Only randomized controlled trials were included in the meta-analysis. The primary outcome was the rate of moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbations. Results: Seven studies fulfilling the inclusion criteria were included in the meta-analysis. Single inhaler triple therapy was associated with a significantly lower risk of COPD exacerbation compared with LABA/LAMA (rate ratio, 0.69; 95% confidence interval [CI] 0.55 to 0.87, I2 =85%), and ICS/LABA (rate ratio, 0.81; 95% CI 0.73 to 0.89, I2 =29%) dual therapy. Single inhaler triple therapy led to a more significant improvement in lung function and quality of life compared with LABA/LAMA and ICS/LABA dual therapy. Single inhaler triple therapy was associated with a higher risk of pneumonia compared with LABA/LAMA (risk ratio, 1.38, 95% CI 1.14 to 1.67, I2 =0) dual therapy. Conclusions: The use of single inhaler triple therapy for COPD patients can result in lower rates of moderate or severe exacerbations of COPD as well as improved lung function and quality of life compared with dual therapy with LABA/LAMA or ICS/LABA.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Progressão da Doença , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Resultado do Tratamento
9.
Ann Saudi Med ; 39(4): 279-282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381360

RESUMO

A 28-month-old boy mistakenly received intranasal atropine sulfate instead of Otrivin (xylometazoline hydrochloride) for the treatment of adenoid hypertrophy. Later on, he came to the emergency department with anticholinergic manifestations after the administration of multiple drops. The child presented with a tonic-clonic seizure lasting for a few minutes, followed by a brief loss of consciousness, vomiting, agitation, and irritability, all of which were stabilized by a dose of intravenous lorazepam. Subsequently, he was admitted to the pediatric intensive care unit for observation. Afterwards, he developed agitation and unsteady gait, both of which resolved after receiving neostigmine. Eventually, the child became asymptomatic and was discharged home. To the best of our knowledge, only one similar case has been reported in the literature. SIMILAR CASES PUBLISHED: 1.


Assuntos
Atropina/envenenamento , Erros de Medicação , Antagonistas Muscarínicos/envenenamento , Administração Intranasal , Atropina/administração & dosagem , Pré-Escolar , Serviço Hospitalar de Emergência , Humanos , Imidazóis/administração & dosagem , Lorazepam/administração & dosagem , Masculino , Antagonistas Muscarínicos/administração & dosagem
10.
Expert Opin Drug Saf ; 18(10): 915-923, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373245

RESUMO

Introduction: Muscarinic receptor antagonists, 5α-reductase inhibitors and α1-adrenoceptor antagonists are frequently used drug classes for the treatment of lower urinary tract symptoms including those of overactive bladder syndrome and benign prostatic enlargement/benign prostatic obstruction. Areas covered: The authors review the evidence for adverse effects of these drug classes on cognitive function, mood and other functions of the central nervous system and discuss such effects against the evidence for mechanistic plausibility. Expert opinion: Muscarinic antagonists carry a risk for impaired cognition and other brain functions that differs quantitatively between compounds, being highest with oral formulations of oxybutynin. 5□-Reductase inhibitors can cause depressive symptoms even at low doses and starting several months after discontinuation of treatment. The evidence for α1-adrenoceptor antagonists and specifically tamsulosin to cause dementia is controversial and lacks mechanistic plausibility. We recommend that physicians treating patients with lower urinary tract symptoms carefully monitor mental status prior to prescribing and periodically thereafter.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Antagonistas Muscarínicos/efeitos adversos , Inibidores de 5-alfa Redutase/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Afeto/efeitos dos fármacos , Animais , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Masculino , Antagonistas Muscarínicos/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/efeitos adversos , Tansulosina/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico
11.
Respir Res ; 20(1): 189, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429756

RESUMO

BACKGROUND: The number of pharmacological agents and guidelines available for COPD has increased markedly but guidelines remain poorly followed. Understanding underlying clinical reasoning is challenging and could be informed by clinical characteristics associated with treatment prescriptions. METHODS: To determine whether COPD treatment choices by respiratory physicians correspond to specific patients' features, this study was performed in 1171 patients who had complete treatment and clinical characterisation data. Multiple statistical models were applied to explain five treatment categories: A: no COPD treatment or short-acting bronchodilator(s) only; B: one long-acting bronchodilator (beta2 agonist, LABA or anticholinergic agent, LAMA); C: LABA+LAMA; D: a LABA or LAMA + inhaled corticosteroid (ICS); E: triple therapy (LABA+LAMA+ICS). RESULTS: Mean FEV1 was 60% predicted. Triple therapy was prescribed to 32.9% (treatment category E) of patients and 29.8% received a combination of two treatments (treatment categories C or D); ICS-containing regimen were present for 44% of patients altogether. Single or dual bronchodilation were less frequently used (treatment categories B and C: 19% each). While lung function was associated with all treatment decisions, exacerbation history, scores of clinical impact and gender were associated with the prescription of > 1 maintenance treatment. Statistical models could predict treatment decisions with a < 35% error rate. CONCLUSION: In COPD, contrary to what has been previously reported in some studies, treatment choices by respiratory physicians appear rather rational since they can be largely explained by the patients' characteristics proposed to guide them in most recommendations.


Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/uso terapêutico , Idoso , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Tomada de Decisão Clínica , Estudos de Coortes , Terapia Combinada , Feminino , Volume Expiratório Forçado , Guias como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/uso terapêutico , Seleção de Pacientes , Médicos , Testes de Função Respiratória , Fatores Sexuais
12.
Int J Chron Obstruct Pulmon Dis ; 14: 1441-1453, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308649

RESUMO

Background: Patients with chronic obstructive pulmonary disease (COPD) show signs of reduced physical activity from the early stages of the disease, impacting morbidity and mortality. Data suggest treatment with tiotropium, a long-acting muscarinic antagonist, and olodaterol, a long-acting ß2-agonist (LABA), as monotherapies and in combination, increases exercise capacity. This study assessed the effects of fixed-dose tiotropium/olodaterol (delivered via Respimat®) on physical function in Global Initiative for Chronic Obstructive Lung Disease A-D patients requiring long-acting dual bronchodilation treatment in a real-world setting. Methods: This open-label, single arm, noninterventional study measured changes in physical function in COPD patients treated with tiotropium/olodaterol 5/5 µg for approximately 6 weeks (between Visit 1 [baseline] and Visit 2). Primary end point was therapeutic success, defined as a minimum 10-point increase in Physical Functioning Questionnaire (PF-10) score. Secondary end points included change in PF-10 from Visit 1 to Visit 2, the patient's general condition (measured by Physician's Global Evaluation score) at Visit 1 and Visit 2, and patient satisfaction with treatment delivered via the Respimat® device (assessed by Patient Satisfaction Questionnaire) at study end. Results: Therapeutic success was observed in 51.5% of 1578 patients (95% confidence interval [CI] 49.0, 54.0) after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 11.6 points (95% CI 10.7, 12.6). Patient general condition improved as indicated by a general improvement in scores between visits. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment (82.5%), inhalation (87.5%), and handling of Respimat® (85.2%). One percent of patients reported an investigator-defined drug-related adverse events (AE). Conclusion: Tiotropium/olodaterol treatment improved physical functioning in COPD patients. An associated increase in patient general condition was observed. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment, inhaling, and handling of the Respimat® device. No unexpected drug-related AE occurred.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Benzoxazinas/administração & dosagem , Broncodilatadores/administração & dosagem , Tolerância ao Exercício/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Benzoxazinas/efeitos adversos , Broncodilatadores/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Nebulizadores e Vaporizadores , Satisfação do Paciente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Brometo de Tiotrópio/efeitos adversos , Resultado do Tratamento
13.
Respir Res ; 20(1): 167, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358008

RESUMO

BACKGROUND: Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). METHODS: In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 µg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 µg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 µg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed. RESULTS: In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range - 0.12 to 0.38%) and P score (LSM range 0.02-0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of -2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs)  was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24. CONCLUSIONS: In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02536508. Registered 27 August 2015.


Assuntos
Densidade Óssea/efeitos dos fármacos , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Glicopirrolato/administração & dosagem , Cristalino/efeitos dos fármacos , Inaladores Dosimetrados/tendências , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Densidade Óssea/fisiologia , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Combinação Budesonida e Fumarato de Formoterol/efeitos adversos , Catarata/induzido quimicamente , Catarata/diagnóstico , Método Duplo-Cego , Feminino , Glicopirrolato/efeitos adversos , Humanos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Cristalino/fisiologia , Masculino , Inaladores Dosimetrados/efeitos adversos , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico
14.
Int J Chron Obstruct Pulmon Dis ; 14: 1377-1388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303751

RESUMO

Background: This study compared real-world patient-reported outcomes (PROs) measured by the Clinical COPD Questionnaire (CCQ), the London Chest Activities of Daily Living (LCADL) scale, and the Work Productivity and Activity Impairment (WPAI) questionnaire between individuals with COPD initiating LAMA/LABA fixed-dose combination (FDC) dual therapy versus either long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) monotherapy. Methods: Individuals with COPD aged ≥40 years initiating a LAMA/LABA FDC dual therapy or a LAMA or LABA monotherapy (index date = first prescription date) between January 1, 2016 and December 31, 2016 were identified from a large US administrative claims database. Individuals were excluded if they were prescribed an inhaled corticosteroid (ICS) or ICS/LABA two months prior to the index date or were diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma. The cohorts were propensity score matched (PSM) 1:1 for COPD severity using baseline measures. Each participant completed a survey. Results: Surveys were completed by 399 participants in the dual therapy cohort, and 718 participants in the monotherapy cohort. Following PSM, 379 participants remained in each cohort for analysis (monotherapy: 369 LAMA and 10 LABA). The dual therapy cohort reported fewer COPD-related symptoms (CCQ symptom score 2.75 vs 2.97, respectively, P=0.023), and, fewer limitations in leisure activities (LCADL leisure score 4.78 vs 5.17, respectively, P=0.021) versus the monotherapy cohort. No significant differences were found in the WPAI. A greater percentage of participants in the dual therapy cohort stayed on index therapy (63.1%) when compared with the monotherapy cohort (30.3%, P<0.0001). Conclusions: Only 30% of the participants prescribed monotherapy, usually with a LAMA, remained on index therapy alone at the time of survey administration. In the dual therapy cohort, 63% of the participants remained on the index medication and had fewer COPD-related symptoms and fewer limitations in leisure activities compared with participants in the monotherapy cohort.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Atividades Cotidianas , Administração por Inalação , Demandas Administrativas em Assistência à Saúde , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Broncodilatadores/efeitos adversos , Efeitos Psicossociais da Doença , Estudos Transversais , Combinação de Medicamentos , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Pulmão/fisiopatologia , Masculino , Antagonistas Muscarínicos/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
15.
Maturitas ; 126: 11-17, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31239111

RESUMO

OBJECTIVES: The aim of this study is to compare the re-treatment probabilities after a 3-month versus a 6-month course of antimuscarinic treatment for women with overactive bladder syndrome (OAB). STUDY DESIGN: A prospective randomized controlled study. MAIN OUTCOME MEASURES: Between-group differences in the probability of re-treatment for OAB between the 3-month and 6-month groups. METHODS: Women with OAB were randomly allocated to receive solifenacin (5 mg per day) for a treatment interval of either 3 or 6 months. RESULTS: Ninety-one patients were treated in each group. The probability of re-treatment did not differ between the 3-month and 6-month groups (P = 0.11). Parity (hazard ratio = 1.81, P = 0.001), number of incontinence episodes (hazard ratio = 1.09, P = 0.008) and suboptimal response (hazard ratio = 3.56, P = 0.006) were independent predictors of re-treatment of OAB. Physical limitation, as indicated on the King's Health Questionnaire, was the only independent factor predicting completion of the scheduled treatment period (odds ratio = 1.01, P = 0.008). CONCLUSIONS: Prolonged antimuscarinic treatment does not decrease the need for re-treatment of OAB. Nonetheless, female patients with increased parity, more severe incontinence and a suboptimal response to antimuscarinic treatment are more likely to seek re-treatment of OAB due to recurrence of symptoms. In addition, patients with more serious physical limitation related to OAB are more likely to complete the scheduled treatment period. These findings could serve as a guide in clinical consultations regarding antimuscarinic treatment and if taken into consideration in future studies could lower the dropout rate.


Assuntos
Antagonistas Muscarínicos/administração & dosagem , Succinato de Solifenacina/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/administração & dosagem , Idoso , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Retratamento , Resultado do Tratamento
16.
Int J Chron Obstruct Pulmon Dis ; 14: 1251-1265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239659

RESUMO

The use of inhaled, fixed-dose, long-acting muscarinic antagonists (LAMA) combined with long-acting, beta2-adrenergic receptor agonists (LABA) has become a mainstay in the maintenance treatment of chronic obstructive pulmonary disease (COPD). One of the fixed-dose LAMA/LABA combinations is the dry powder inhaler (DPI) of umeclidinium bromide (UMEC) and vilanterol trifenatate (VI) (62.5 µg/25 µg) approved for once-a-day maintenance treatment of COPD. This paper reviews the use of fixed-dose combination LAMA/LABA agents focusing on the UMEC/VI DPI inhaler in the maintenance treatment of COPD. The fixed-dose combination LAMA/LABA inhaler offers a step beyond a single inhaled maintenance agent but is still a single device for the COPD patient having frequent COPD exacerbations and persistent symptoms not well controlled on one agent. Currently available clinical trials suggest that the once-a-day DPI of UMEC/VI is well-tolerated, safe and non-inferior or better than other currently available inhaled fixed-dose LAMA/LABA combinations for COPD.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Álcoois Benzílicos/administração & dosagem , Broncodilatadores/administração & dosagem , Clorobenzenos/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/farmacocinética , Álcoois Benzílicos/efeitos adversos , Álcoois Benzílicos/farmacocinética , Broncodilatadores/efeitos adversos , Broncodilatadores/farmacocinética , Clorobenzenos/efeitos adversos , Clorobenzenos/farmacocinética , Combinação de Medicamentos , Inaladores de Pó Seco , Medicina Baseada em Evidências , Humanos , Pulmão/fisiopatologia , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacocinética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinuclidinas/efeitos adversos , Quinuclidinas/farmacocinética , Recuperação de Função Fisiológica , Resultado do Tratamento
17.
Invest Ophthalmol Vis Sci ; 60(7): 2623-2630, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31226711

RESUMO

Purpose: To explore the effect of topical atropine on axial eye growth and emmetropization in infant marmosets. Methods: Atropine was applied to one eye from the age of 7 to 56 days in two dose regimens, High (0.1-1% twice daily, increasing with age) or moderate (Mod) (0.1% once daily). Both eyes of the marmosets were refracted, and axial dimensions were measured ultrasonically, at 14, 28, 42, 49, 56, 70, 105, 168, and 279 days of age. The time course of each measured variable was analyzed using multilevel mixed-effects modeling realized in R. Results: The logistic growth curves fitted to anterior segment depth (ASD) did not differ significantly between the dose regimens, but xmid, the age at which growth was half-maximal, and scal, the time constant of the exponential term in the logistic growth curve equation, differed significantly between the ASD of atropinized and untreated eyes (P = 0.03 and P < 0.0001, respectively), with the ASD of atropinized eyes shorter than that of untreated eyes. The splines fitted to lens thickness did not vary significantly with dose, but differed significantly (P < 0.0001) between the atropinized and untreated eyes, with the atropinized lenses thicker. Vitreous chamber depth (VCD) was not significantly different, but the variance of VCD was significantly greater (P < 0.001) in the atropinized compared with the untreated eyes. Refractive error (RE) became relatively myopic in atropinized eyes. The variance of RE in atropinized eyes was significantly greater (P < 0.0001) than in untreated eyes. Conclusions: Atropine caused the infant marmoset lens to move forward and thicken, a relative myopia, and increases in the between-animals variance in VCD, which could be considered a failure of emmetropization.


Assuntos
Atropina/administração & dosagem , Comprimento Axial do Olho/efeitos dos fármacos , Olho/crescimento & desenvolvimento , Antagonistas Muscarínicos/administração & dosagem , Miopia/etiologia , Acomodação Ocular/efeitos dos fármacos , Acomodação Ocular/fisiologia , Administração Oftálmica , Animais , Animais Recém-Nascidos , Callithrix , Emetropia/fisiologia , Masculino , Miopia/fisiopatologia , Soluções Oftálmicas , Retinoscopia , Corpo Vítreo/efeitos dos fármacos
18.
Int J Chron Obstruct Pulmon Dis ; 14: 1167-1176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213796

RESUMO

Background: Dynamic lung hyperinflation (DLH) following metronome-paced incremental hyperventilation (MPIH) was reported to be useful for assessment of pathophysiological impairment in patients with chronic obstructive pulmonary disease (COPD), and the effects of tiotropium and olodaterol on DLH following MPIH have not been reported. Methods: Treatment consisted of administration of tiotropium/olodaterol 5/5 µg inhalation solution (2.5/2.5 µg per actuation) using a soft-mist inhaler once a day. We compared outcomes before and after 8 weeks of treatment. The primary outcome was defined as a decrease in inspiratory capacity (IC) from rest by MPIH, which is an index of DLH. The secondary outcomes were COPD assessment test (CAT), forced expiratory volume in 1 s (FEV1), and 6-min walking distance (6MWD). In addition, we investigated whether there were correlations between changes with treatment in DLH and FEV1, 6MWD, and dyspnea. Results: Thirty-three of the 38 registered patients completed this study. Most of these 33 patients had mild to moderate COPD. Decreasing IC by MPIH was significantly reduced by treatment for 8 weeks, with a mean change of about -0.11 to -0.13 mL (P <0.05). In addition, CAT score, FEV1, and 6MWD improved with treatment (P <0.05). There were no significant correlations between changes in DLH, FEV1, 6MWD, or dyspnea with treatment. Conclusions: The results of this study showed that the combination of tiotropium and olodaterol is effective for improvement of DLH following hyperventilation.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Benzoxazinas/administração & dosagem , Broncodilatadores/administração & dosagem , Dispneia/tratamento farmacológico , Hiperventilação/fisiopatologia , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Benzoxazinas/efeitos adversos , Broncodilatadores/efeitos adversos , Combinação de Medicamentos , Dispneia/diagnóstico , Dispneia/fisiopatologia , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Hiperventilação/diagnóstico , Japão , Pulmão/fisiopatologia , Masculino , Antagonistas Muscarínicos/efeitos adversos , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Brometo de Tiotrópio/efeitos adversos , Resultado do Tratamento
19.
Artigo em Inglês | MEDLINE | ID: mdl-31114180

RESUMO

Background: There are currently limited real-world data on the clinical burden of illness in patients with COPD who continue to exacerbate despite receiving triple therapy. The aim of this study was to compare the burden of COPD in patients with and without a phenotype characterized by a high blood eosinophil count and high risk of exacerbations while receiving triple therapy. Methods: This retrospective cohort study (GSK ID: 207323/PRJ2647) used UK Clinical Practice Research Datalink records linked with Hospital Episode Statistics. Eligible patients had a COPD medical diagnosis code recorded between January 1, 2004 and December 31, 2014, and a blood eosinophil count recorded on/after that date. Patients were followed from index date (first qualifying blood eosinophil count) until December 31, 2015. The study phenotype was defined as ≥2 moderate/≥1 severe acute exacerbation of COPD (AECOPD) in the year prior to the index date, current use of multiple-inhaler triple therapy (MITT), and blood eosinophil count ≥150 cells/µL on the index date. Outcomes measured during follow-up included moderate/severe AECOPDs, severe AECOPDs, all-cause mortality, primary care (GP) clinical consultations, and non-AECOPD-related unscheduled hospitalizations. Results: Of 46,814 patients eligible for inclusion, 2512 (5.4%) met the definition of the study phenotype. Adjusted rate ratios (95% CI) of moderate/severe AECOPDs and all-cause mortality in patients with the study phenotype versus those without were 2.32 (2.22, 2.43) and 1.26 (1.16, 1.37), respectively. For GP visits and non-AECOPD-related unscheduled hospitalizations, adjusted rate ratios (95% CI), in patients with the study phenotype versus those without, were 1.09 (1.05, 1.12) and 1.31 (1.18, 1.46), respectively. Conclusion: Patients with COPD and raised blood eosinophil counts who continue to exacerbate despite MITT represent a distinct subgroup who experience substantial clinical burden and account for high healthcare expenditure. There is a need for more effective management and therapeutic options for these patients.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Efeitos Psicossociais da Doença , Eosinofilia/sangue , Eosinófilos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Progressão da Doença , Quimioterapia Combinada , Eosinofilia/diagnóstico , Eosinofilia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Fenótipo , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Reino Unido/epidemiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-31114181

RESUMO

Background: Long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs) are the mainstay of maintenance therapy for chronic obstructive pulmonary disease (COPD). Although previous studies have supported inhaled long-acting bronchodilators (ILABs) for overall cardiovascular safety, the risk of specific cardiovascular outcomes such as arrhythmia, heart failure and stroke is still unknown. Materials and methods: We systematically searched from PubMed, the Embase database and the Cochrane Library for published studies on ILABs and COPD, from its inception to November 10, 2018, with no language restrictions. The RRs and corresponding 95% CIs were pooled to evaluate ILAB/placebo. Results: Finally, 43 randomized controlled trials were included. Compared with placebo, ILABs do not increase the risk of overall and specific cardiovascular adverse events (AEs); on the contrary, they can reduce the incidence of hypertension (RR 0.73, 95% CI 0.55-0.98;I219.9%; P= 0.221). However, when stratified according to the specific agents of ILABs, olodaterol might reduce the risk of overall cardiovascular adverse events (OCAEs) (RR 0.65, 95% CI 0.49-0.88;I227.5%; P= 0.000), and the protective effect of lowing blood pressure disappeared. Similarly, the use of inhaled LABA might increase the risk of cardiac failure (RR 1.71, 95% CI 1.04-2.84;I20%; P= 0.538), but this risk disappeared when stratified according to the specific agents of LABA. Besides, formoterol might decrease the risk of cardiac ischemia (RR 0.53, 95% CI 0.32-0.91; I20%; P= 0.676). Conclusions: Overall, the use of ILABs was not associated with overall cardiovascular AEs in patients with stable COPD. When stratified according to the specific agents of LABA, olodaterol might reduce the risk of OCAE; and formoterol might decrease the risk of cardiac ischemia. LABA might reduce the incidence of hypertension, but might increase the risk of heart failure. Therefore, COPD patients with a history of heart failure should use it with caution.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Doenças Cardiovasculares/epidemiologia , Sistema Cardiovascular/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Broncodilatadores/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/fisiopatologia , Esquema de Medicação , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Pulmão/fisiopatologia , Antagonistas Muscarínicos/efeitos adversos , Fatores de Proteção , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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