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1.
Toxicol Lett ; 325: 67-76, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017982

RESUMO

Racemic 3-quinuclidinyl-α-methoxydiphenylacetate (MB266) was synthesised. Its activity at muscarinic acetylcholine receptors (mAChRs), and muscle and neuronal nicotinic acetylcholine receptors (nAChRs), was compared to that of atropine and racemic 3-quinucidinyl benzilate (QNB) using a functional assay based on agonist-induced elevation of intracellular calcium ion concentration in CN21, Chinese Hamster Ovary (CHO) and SHSY5Y human cell lines. MB266 acted as an antagonist at acetylcholine receptors, displaying 18-fold selectivity for mAChR versus nAChR (compared to the 15,200-fold selectivity observed for QNB). Thus O-methylation of QNB reduced the affinity for mAChR antagonism and increased the relative potency at both muscle and neuronal nAChRs. Despite MB266 having a pharmacological profile potentially useful for the treatment of anticholinesterase poisoning, its administration did not improve the neuromuscular function in a soman-poisoned guinea-pig diaphragm preparation pretreated with the organophosphorus nerve agent soman. Consideration should be given to exploring the potential of MB266 for possible anticonvulsant action in vitro as part of a multi-targeted ligand approach.


Assuntos
Antídotos/farmacologia , Antídotos/uso terapêutico , Inibidores da Colinesterase/envenenamento , Antagonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/uso terapêutico , Agentes Neurotóxicos/envenenamento , Antagonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/uso terapêutico , Animais , Anticonvulsivantes/química , Anticonvulsivantes/uso terapêutico , Antídotos/síntese química , Células CHO , Linhagem Celular , Cricetinae , Cricetulus , Diafragma/efeitos dos fármacos , Cobaias , Humanos , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/síntese química , Músculo Esquelético/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Antagonistas Nicotínicos/síntese química , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Soman/envenenamento
2.
Expert Opin Pharmacother ; 21(2): 213-231, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31955671

RESUMO

Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a disease phenotype that shares T helper lymphocyte cell Th1/neutrophilic/non-Type-2 Inflammation pathways thought to be key in COPD and Th2/eosinophilic/Type-2 inflammatory pathways of asthma. The pharmacology of treating ACOS is challenging in severe circumstances.Areas covered: This review evaluates the stepwise treatment of ACOS using pharmacological treatments used in both COPD and asthma. The most common medications involve the same inhalers used to treat COPD and asthma patients. Advanced stepwise therapies for ACOS patients are based on patient characteristics and biomarkers. Very few clinical trials exist that focus specifically on ACOS patients.Expert opinion: After inhalers, advanced therapies including phosphodiesterase inhibitors, macrolides, N-acetylcysteine and statin therapy for those ACOS patients with a COPD appearance and exacerbations are available. In atopic ACOS patients with exacerbations, advanced asthma therapies (leukotriene receptor antagonists and synthesis blocking agents.) are used. ACOS patients with elevated blood eosinophil/IgE levels are considered for immunotherapy or therapeutic monoclonal antibodies blocking specific Th2/Type-2 interleukins or IgE. Symptom control, stabilization/improvement in pulmonary function and reduced exacerbations are the metrics of success. More pharmacological trials of ACOS patients are needed to better understand which patients benefit from specific treatments.Abbreviations: 5-LOi: 5-lipoxygenase inhibitor; ACOS: asthma - COPD overlap syndrome; B2AR: Beta2 adrenergic receptors; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRS : chronic rhinosinusitis; cys-LT: cysteinyl leukotrienes; DPI: dry powder inhaler; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: fixed-dose combination; FeNO: exhaled nitric oxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICS : inhaled corticosteroids; IL: interleukin; ILC2: Type 2 innate lymphoid cells; IP3: Inositol triphosphate; IRR: incidence rate ratio; KOLD: Korean Obstructive Lung Disease; LABA: long-acting B2 adrenergic receptor agonist; LAMA: long-acting muscarinic receptor antagonist; LRA: leukotriene receptor antagonist; LT: leukotrienes; MDI: metered-dose inhalers; MN: M-subtype muscarinic receptors; MRA: muscarinic receptor antagonist; NAC: N-acetylcysteine; NEB: nebulization; OR: odds ratio; PDE: phosphodiesterase; PEFR: peak expiratory flow rate; PGD2: prostaglandin D2; PRN: as needed; RR: risk ratio; SABA: short-acting B2 adrenergic receptor agonist; SAMA: short-acting muscarinic receptor antagonist; SDMI: spring-driven mist inhaler; Th1: T helper cell 1 lymphocyte; Th2: T helper cell 2 lymphocytes; TNF-α: tumor necrosis factor alpha; US : United States.


Assuntos
/tratamento farmacológico , Broncodilatadores/uso terapêutico , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Volume Expiratório Forçado , Humanos , Antagonistas Muscarínicos/uso terapêutico , Nebulizadores e Vaporizadores , Capacidade Vital
3.
Curr Urol Rep ; 20(11): 75, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707521

RESUMO

PURPOSE OF REVIEW: Nocturia is defined as awakening due to the desire to void during a period of intended sleep. The pathophysiology of nocturia is multifactorial and management remains a challenge. Herein, we provide an overview of the management strategies for nocturia and summarize the existing evidence for treatment of nocturia across the condition's broad etiologic categories: nocturnal polyuria, diminished bladder capacity, and global polyuria. RECENT FINDINGS: Treatment should begin with behavioral modification. A high level of evidence supports the efficacy of desmopressin in the treatment of nocturnal polyuria. Data supporting the efficacy of α-blockers, antimuscarinics, and surgical bladder outlet procedures in the treatment of nocturia remains limited. Treatment options for nocturia are determined by underlying mechanism. Desmopressin is effective in treating nocturnal polyuria. Surgical intervention, α-blockers, and antimuscarinics may improve nocturia when associated with lower urinary tract symptoms or overactive bladder in the setting of diminished bladder capacity.


Assuntos
Noctúria/etiologia , Noctúria/terapia , Bexiga Urinária/patologia , Antagonistas Adrenérgicos alfa/uso terapêutico , Antidiuréticos/uso terapêutico , Terapia Comportamental , Desamino Arginina Vasopressina/uso terapêutico , Humanos , Sintomas do Trato Urinário Inferior/complicações , Antagonistas Muscarínicos/uso terapêutico , Tamanho do Órgão , Poliúria/complicações , Bexiga Urinária Hiperativa/complicações
4.
FP Essent ; 486: 26-32, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31710455

RESUMO

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease characterized by cough, dyspnea, and sputum production caused by inhalation of harmful chemicals, such as tobacco smoke. COPD should be suspected in patients with a significant smoking history, shortness of breath, and sputum production. The diagnosis is made by spirometry. A forced expiratory volume in the first second of expiration to forced vital capacity (FEV1/FVC) ratio of less than 0.7 after bronchodilator administration confirms the diagnosis. Therapy for patients with stable COPD should include a bronchodilator, either a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). For patients who continue to experience dyspnea with a single bronchodilator, dual therapy with a LABA and LAMA is appropriate. For patients with continued exacerbations, inhaled corticosteroids can be added to LABA-LAMA therapy. Acute exacerbations are characterized by a worsening of symptoms that requires additional therapy. Short-acting beta2-agonists with or without short-acting muscarinic antagonists are the basic therapy for acute exacerbations of COPD. Systemic glucocorticoids have been shown to shorten exacerbations and improve lung function. Antibiotics have been shown to reduce rates of treatment failure and sputum purulence. Noninvasive mechanical ventilation is preferred for patients with respiratory failure.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado , Humanos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
7.
Medicina (Kaunas) ; 55(9)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540331

RESUMO

Background and Objectives: Atropine is a nonselective muscarinic antagonist which has been used to prevent worsening of myopia in children. Different concentrations of atropine were used for myopia, ranging from 0.01% to 1.0%. However, there are still potential toxicity of different doses of atropine to the cornea. Here, we present a study of investigating novel genes potentially involved in the effects of very low dose atropine treatment (0.003%) on corneal epithelial cells using next-generation sequencing (NGS) and bioinformatics approaches. Materials and Methods: Human corneal epithelial cells were treated with 0.003% atropine, cultured until confluence, and RNA extracted for differential expression profiling of mRNA and microRNA (miRNA) between control and atropine-treated corneal epithelial cells. The functional enrichment analysis for differentially expressed genes was performed using two bioinformatics databases, including Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity® Pathway Analysis (IPA). In addition, potential miRNA-mRNA interactions involved in atropine-treated corneal epithelial cells were predicted and validated using different miRNA target prediction databases. Results: Our results showed 0.003% atropine might suppress the apoptosis of corneal epithelial cells, potentially through Ras and protein kinase A signaling pathways. We also validated the possible miRNA regulations by using TargetScan and miRDB databases. Hsa-miR-651-3p-EPHA7, hsa-miR-3148-TMEM108 and hsa-miR-874-5p-TBX6 were validated as possible miRNA regulations involved in corneal epithelial cells treated with 0.003% atropine. Conclusions: These findings may contribute novel insights into therapeutic strategies for treating cornea with 0.003% atropine.


Assuntos
Atropina/farmacologia , Córnea/citologia , Células Epiteliais/efeitos dos fármacos , MicroRNAs/genética , Antagonistas Muscarínicos/farmacologia , Atropina/uso terapêutico , Biologia Computacional , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/efeitos dos fármacos , Antagonistas Muscarínicos/uso terapêutico , Miopia/tratamento farmacológico
9.
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
10.
Herz ; 44(6): 517-521, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297545

RESUMO

Chronic heart and lung diseases are very common in the elderly population. The combination of chronic heart failure and chronic obstructive pulmonary disease (COPD) is also common and, according to current guidelines, these patients should be treated for both diseases. In patients with heart failure, beta-blockers are very important drugs because their use is associated with significantly improved morbidity and mortality. These beneficial effects were documented in patients with and without COPD, although theoretically there is a risk for bronchoconstriction, particularly with non-beta1 selective blockers. In COPD patients, long-acting sympathomimetics (LABA) improve lung function, dyspnea, and quality of life and their combination with a beta-blocker makes sense from a pharmacological and a clinical point of view, because any potential arrhythmogenic effects of the LABA will be ameliorated by the beta-blocker. Inhaled tiotropium, a long-acting muscarinic antagonist (LAMA), has been extensively investigated and no safety concerns were reported in terms of cardiac adverse effects. The same applies for the other approved LAMA preparations and LAMA-LABA combinations. Severe COPD causes air-trapping with increasing pressures in the thorax, leading to limitations in blood return into the thorax from the periphery of the body. This causes a decrease in stroke volume and cardiac index and is associated with dyspnea. All these adverse effects can be ameliorated by potent anti-obstructive therapy as recently shown by means of a LABA-LAMA combination.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Interações de Medicamentos , Humanos , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida
11.
Geriatr Gerontol Int ; 19(9): 913-917, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342625

RESUMO

AIM: Alzheimer's disease is a common cause of dementia, and is usually treated with medications that elevate acetylcholine levels. The objective of the present study was to identify drugs with anticholinergic properties prescribed to patients diagnosed with Alzheimer's disease in Colombia. METHODS: A cross-sectional study was carried out in outpatients diagnosed with Alzheimer's disease who were identified from a population database from Colombia, and had been treated with cholinesterase inhibitors and glutamate N-methyl-D-aspartate receptor antagonists. The anticholinergic burden was evaluated using the Anticholinergic Cognitive Burden scale, and patients were classified on a scale of 0-3 points according to anticholinergic potential, and were grouped into those with mild-to-moderate (1-2 points) or high (≥3 points) anticholinergic load. RESULTS: The study included 4134 Alzheimer's disease patients. The mean age was 81.50 ± 8.16 years, and 67.8% were women. At least 22.9% of patients took anticholinergic drugs. Of these, the most frequently prescribed medication was quetiapine (8.6%). Age >85 years was associated with a high risk of having an anticholinergic burden ≥3 points (OR 2.19, 95%CI 1.159-4.162). Potential interactions between cholinesterase inhibitors and anticholinergic drugs were identified in 7.8% of patients. CONCLUSIONS: The majority of patients who were prescribed anticholinergic drugs were older women, had a significant total anticholinergic burden and had frequent pharmacological interactions with cholinesterase inhibitors. The use of anticholinergics reduces the clinical effectiveness of antidementia drugs and increases the risk of adverse reactions. Geriatr Gerontol Int 2019; 19: 913-917.


Assuntos
Doença de Alzheimer , Inibidores da Colinesterase/uso terapêutico , Prescrição Inadequada , Antagonistas Muscarínicos/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/epidemiologia , Antagonistas Colinérgicos/uso terapêutico , Colômbia/epidemiologia , Estudos Transversais , Feminino , Humanos , Prescrição Inadequada/prevenção & controle , Prescrição Inadequada/estatística & dados numéricos , Masculino , Conduta do Tratamento Medicamentoso/normas , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Pacientes Ambulatoriais/estatística & dados numéricos , Farmacovigilância , Lista de Medicamentos Potencialmente Inapropriados , Psicotrópicos/uso terapêutico
13.
Respir Res ; 20(1): 141, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286970

RESUMO

There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease. This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls. However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials. Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Volume Expiratório Forçado/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Tolerância ao Exercício/fisiologia , Volume Expiratório Forçado/fisiologia , Humanos , Antagonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Resultado do Tratamento
15.
Arch. Soc. Esp. Oftalmol ; 94(6): 285-287, jun. 2019.
Artigo em Espanhol | IBECS | ID: ibc-185048

RESUMO

Se describe un caso probable de espasmo de acomodación aislado unilateral en una niña de 10 años sin antecedentes de relevancia. Presentó disminución de agudeza visual en el ojo derecho (OD) que variaba entre 0,2-0,6 y de cerca (Rossano Weiss) 0,125. La refracción sin cicloplejía era de OD -6 dioptrías (D) y OI + 0,25 D y con cicloplejía OD + 0,5 D OI + 0,75 D. Presentó ortotropía, ducciones y versiones normales. Pupilas isocóricas, reactivas a la luz, segmento anterior y posterior, la tomografía de coherencia óptica, estudios neurofisiológicos (potenciales evocados, electrorretinograma y electroculograma) y resonancia magnética craneal normales. Se prescribió atropina 1% en OD durante 15 días mejorando la agudeza visual de lejos 0,8 y cerca 0,25. El espasmo de la acomodación es una situación rara y suele ser bilateral. Puede estar asociado a traumatismos craneales u oculares por lo que las pruebas de imagen son necesarias. El tratamiento consiste en fármacos ciclopléjicos (atropina, ciclopentolato), sin embargo, no existe una pauta definida


This case report describes a probable unilateral accommodation spasm in a 10 year-old girl with no significant medical history. The right eye showed decreased visual acuity, 0.2 to 0.6 for far distance and 0.125 for near distance. Refraction without cycloplegia showed myopization up to -6 and cycloplegic refraction of + 0.50. The patient had normal ocular motility, orthophoria, normal pupil reflex, normal anterior and posterior segments, normal optical coherence tomography. Neurophysiological tests and brain magnetic resonance imaging were all normal. Treatment with atropine 1% drops for 15 days improved distance visual acuity to 0.8. Accommodation spasm is a rare condition and is usually bilateral. Imaging test are necessary because it may be associated with ocular or head trauma. Treatment consists of cycloplegic drugs (atropine, cyclopentolate); however, there is no defined guideline


Assuntos
Humanos , Feminino , Criança , Acomodação Ocular , Atropina/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Espasmo/diagnóstico , Espasmo/tratamento farmacológico
16.
Drugs ; 79(9): 997-1008, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31119643

RESUMO

Tiotropium/olodaterol (Stiolto® Respimat®; Spiolto® Respimat®) is an inhaled fixed-dose combination of the long-acting muscarinic antagonist tiotropium bromide (hereafter referred to as tiotropium) and the long-acting ß2-adrenergic agonist olodaterol. It is available in several countries, including the USA, Japan, China and those of the EU, where it is indicated for the long-term maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). The efficacy of tiotropium/olodaterol 5/5 µg/day in patients with COPD was evaluated in phase III or IV trials of 6-52 weeks' duration. Tiotropium/olodaterol improved lung function to a greater extent than each of its individual components or placebo in 12- and 52-week trials. In 6-week trials, tiotropium/olodaterol provided greater lung function benefits over 24 h than the individual components, placebo or twice-daily fluticasone propionate/salmeterol. Tiotropium/olodaterol also demonstrated beneficial effects on health-related quality of life (HR-QoL), dyspnoea, inspiratory capacity, exercise endurance and the need for rescue medication. In an 8-week open-label trial, umeclidinium/vilanterol was superior to tiotropium/olodaterol for the primary endpoint of trough forced expiratory volume in 1 s. The tolerability profile of tiotropium/olodaterol was generally similar to that of the individual components. In conclusion, tiotropium/olodaterol provides a useful option for the maintenance treatment of COPD, with the convenience of once-daily administration via a single inhaler.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Benzoxazinas/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/uso terapêutico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Benzoxazinas/farmacologia , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Fase IV como Assunto , Combinação de Medicamentos , Humanos , Antagonistas Muscarínicos/farmacologia , Qualidade de Vida , Brometo de Tiotrópio/farmacologia , Resultado do Tratamento
17.
Curr Urol Rep ; 20(6): 33, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31098731

RESUMO

Overactive bladder syndrome (OAB) negatively affects the quality of life of patients and their interactions with society. Treatment of OAB starts with behavioral modification and then pharmacotherapy using monotherapy with either antimuscarinics or ß3 agonists. The third-line more invasive approaches are the next treatment option currently recommended. Both antimuscarinic agents and ß3 agonists work through a different molecular pathway. This brings up the potential of having an additive effect when using a combination treatment for patients with OAB. Currently, the potential for using combination therapy to treat OAB in patients who had no improvement with a monotherapy approach before we attempt a more invasive approach is being explored. Several studies have shown the benefits of combination therapy which will be an additional option to the tools to treat OAB.


Assuntos
Terapia Comportamental/métodos , Antagonistas Muscarínicos/uso terapêutico , Qualidade de Vida , Bexiga Urinária Hiperativa/terapia , Humanos
18.
Ter Arkh ; 91(3): 76-85, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31094464

RESUMO

Currently, combinations of long-acting beta2-agonists and long-acting anticholinergics are considered as the basic therapy for majority of patients with chronic obstructive pulmonary disease (COPD). These combinations have different pharmacological characteristics and delivery devices that provides different clinical effects and new opportunities for personalized treatment of COPD. Aclidinium/formoterol fixed combination differs from other dual bronchodilators by twice-daily dosing regimen, good safety profile and a specific delivery system. Recent information on clinical efficacy and safety of aclidinium/formoterol combination in COPD patients is given in this article.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/uso terapêutico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Combinação de Medicamentos , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/efeitos adversos , Humanos , Pulmão/fisiopatologia , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Resultado do Tratamento , Tropanos/administração & dosagem , Tropanos/efeitos adversos
19.
JAMA ; 321(17): 1693-1701, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063575

RESUMO

Importance: There is concern that long-acting muscarinic antagonists increase cardiovascular morbidity or mortality in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine the cardiovascular safety (noninferiority) and efficacy (superiority) of aclidinium bromide, 400 µg twice daily, in patients with COPD and cardiovascular disease or risk factors. Design, Setting, and Participants: Multicenter, randomized, placebo-controlled, double-blind, parallel-design study conducted at 522 sites in North America. A total of 3630 patients with moderate to very severe COPD and either a history of cardiovascular disease or at least 2 atherothrombotic risk factors were randomized; follow-up occurred for up to 3 years until at least 122 major adverse cardiovascular events (MACE) occurred. The first patient was enrolled on October 16, 2013 and the last on August 22, 2016. The final patient completed follow-up on September 21, 2017. Interventions: Patients were randomized to receive aclidinium (n = 1812) or placebo (n = 1818) by dry-powder inhaler, twice daily for up to 3 years. Main Outcomes and Measures: The primary safety end point was time to first MACE over up to 3 years (hazard ratio [HR] 1-sided 97.5% CI noninferiority margin = 1.8). The primary efficacy end point was the annual COPD exacerbation rate during the first year of treatment. Secondary outcomes included an expanded MACE definition (time to first MACE or serious cardiovascular event of interest) and annual rate of exacerbations requiring hospitalization. Results: Among 3589 patients analyzed (mean age, 67.2 years; 58.7% male), 2537 (70.7%) completed the study. Of these, 69 (3.9%) aclidinium and 76 (4.2%) placebo patients had a MACE (HR, 0.89; 1-sided 97.5% CI, 0-1.23); the expanded MACE definition included 168 (9.4%) aclidinium vs 160 (8.9%) placebo patients with events (HR, 1.03; 1-sided 97.5% CI, 0-1.28). Annual moderate to severe exacerbation rates (aclidinium, 0.44; placebo, 0.57; rate ratio, 0.78; 2-sided 95% CI, 0.68-0.89; P < .001) and rate of exacerbations requiring hospitalization (aclidinium, 0.07; placebo, 0.10; rate ratio, 0.65; 2-sided 95% CI, 0.48-0.89; P = .006) decreased significantly with aclidinium vs placebo. The most common adverse events were pneumonia (aclidinium, 109 events [6.1%]; placebo, 105 events [5.8%]), urinary tract infection (aclidinium, 93 events [5.2%]; placebo, 89 events [5.0%]), and upper respiratory tract infection (aclidinium, 86 events [4.8%]; placebo, 101 events [5.6%]). Conclusions and Relevance: Among patients with COPD and increased cardiovascular risk, aclidinium was noninferior to placebo for risk of MACE over 3 years. The rate of moderate to severe COPD exacerbations was reduced over the first year. Trial Registration: ClinicalTrials.gov Identifier: NCT01966107.


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/uso terapêutico , Administração por Inalação , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Gravidade do Paciente , Fatores de Risco , Tropanos/efeitos adversos
20.
Int Braz J Urol ; 45(4): 782-789, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136113

RESUMO

PURPOSE: To evaluate the efficacy and tolerability of mirabegron in females with overactive bladder (OAB) symptoms after surgical treatment for stress urinary incontinence (SUI). MATERIALS AND METHODS: The study was conducted with a prospective, randomized and double-blinded design. 62 patients over the age of 40 who met the inclusion-exclusion criterias of the study were enrolled and randomly divided into two groups as Group A (mirabegron 50mg) and B (solifenacin 5mg). Patients were compared based on efficacy of treatment [Patient Perception of Bladder Condition (PPBC) scale and micturition diaries], safety of treatment (heart rate, systolic and diastolic blood pressure, adverse events), number of micturitions per day, patient's satisfaction status after treatment [Visual Analog Scale(VAS)] and quality of life. RESULTS: The mean age of the population was 48.2±3.8 years and the duration of OAB symptoms was 5.9±2.9 months. Baseline values for the mean number of micturitions, volume voided in each micturition, nocturia episodes, urgency and urgency incontinence episodes were 15.3±0.34, 128±3.88mL, 3.96±1.67, 5.72±1.35 and 4.22±0.69, respectively. After treatment, values for these parameters were 11.7±0.29, 164.7±2.9mL, 2.25±0.6, 3.38±0.71, 2.31±0.49 respectively. Quality of life score, symptom bother score, VAS for treatment satisfaction score, PPBC score after treatment were 66.1±0.85, 43.7±0.77, 4.78±0.14, 4.78±0.14, respectively. There were no significant differences between two groups on any parameter. However, mirabegron showed better tolerability than solifenacin, particularly after 6 months. CONCLUSION: Mirabegron is safe, effective and tolerable in the long-term treatment of females with OAB symptoms after surgery for stress urinary incontinence.


Assuntos
Acetanilidas/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária por Estresse/cirurgia , Adulto , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Antagonistas Muscarínicos/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Valores de Referência , Reprodutibilidade dos Testes , Succinato de Solifenacina/uso terapêutico , Resultado do Tratamento , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária por Estresse/fisiopatologia , Escala Visual Analógica
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