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1.
Rev Assoc Med Bras (1992) ; 65(11): 1343-1348, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31800894

RESUMO

OBJECTIVE: To evaluate chronological age as a limiting factor to perform the bronchodilator test, determine significant adverse effects of short-acting beta 2 agonists with clinical repercussions, and assess bronchodilator response in extreme-old-age patients who undergo the spirometry test. METHODS: This is a cross-sectional and retrospective study. The sample was extracted from the database (spirometer and respiratory questionnaire) of a pulmonary function service. Patients over 90 years old were included in the research, and we evaluated their bronchodilator response and its significant adverse effects that may have clinical repercussions related to the bronchodilator. RESULTS: A sample of 25 patients aged 92.12 ± 2.22 years (95% CI, 91.20 - 93.04), with a minimum age of 90 years and a maximum of 97 years and a predominance of females with 72% (18/25). The bronchodilator test was performed in 84% (21/25) of the patients. The bronchodilator response was evaluated in 19 of the 21 patients (90.47%) who underwent the bronchodilator test. Two tests did not meet the criteria of acceptability and reproducibility. No clinical adverse effects were observed with the bronchodilator medication (salbutamol) during or after the exam. CONCLUSIONS: Chronological age is not a limiting factor for the bronchodilator test, short-acting beta-2 agonists did not present adverse effects with significant clinical repercussion and were useful in the diagnosis and therapeutic guidance of extreme-old-age patients.


Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Envelhecimento , Testes de Provocação Brônquica/métodos , Broncodilatadores/administração & dosagem , Espirometria/métodos , Agonistas Adrenérgicos beta/efeitos adversos , Idoso de 80 Anos ou mais , Testes de Provocação Brônquica/efeitos adversos , Broncodilatadores/efeitos adversos , Estudos Transversais , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Espirometria/efeitos adversos
2.
Ter Arkh ; 91(1): 78-83, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090376

RESUMO

AIM: The aim of the study. To estimate the effectiveness of clinical patients register implementation as well as to analyze different treatment and prophylactic programs on chronic obstructive pulmonary disease (COPD) patients' structure. MATERIALS AND METHODS: The COPD patient's register consists of 4257 cases. Spirometrical data were evaluated. Dynamic follow was performed on 567 COPD patients. Bronchodilator's therapy was estimated as well as combined inhaled corticosteroid/ long acting ß2-agonist medications and vaccination against pneumococcal infection. RESULTS: Computer program "Electronic polyclinic" proposed by the authors of this article is effective in precision of diagnostic decision making in cohort study, dynamic follow up after clinical symptoms, evaluation of instrumental and laboratory results, prophylactics and treatment effectiveness, "clinical patients registers" automatic formation using syndrome or nosological principle, checking the COPD patients in the group of those with bronchial obstruction. CONCLUSION: Positive effects of long-acting bronchodilator treatment on COPD exacerbation decreasing and more expressed effect of inhaled corticosteroid/ long acting ß2-agonists were confirmed. More interesting result was influence of vaccination against pneumococcal infection PCV13 (polyvalent conjugated vaccine) on exacerbation frequency and dyspnea severity.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas Adrenérgicos beta/efeitos adversos , Agonistas Adrenérgicos beta/uso terapêutico , Broncodilatadores/efeitos adversos , Broncodilatadores/uso terapêutico , Estudos de Coortes , Seguimentos , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Sistema de Registros , Resultado do Tratamento
3.
Clin Perinatol ; 46(2): 203-213, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010556

RESUMO

Many conditions that require frequent medication use are common during pregnancy. The purpose of this article is to list some of the most common of these disorders and to discuss the risk to the developing fetus of the medications used most frequently to treat them. Included are drugs used for the treatment of asthma, nausea and vomiting, hyperthyroidism, pain and fever, and depression during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Congênitas/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/prevenção & controle , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/efeitos adversos , Agonistas Adrenérgicos beta/uso terapêutico , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos não Entorpecentes/uso terapêutico , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Antitireóideos/efeitos adversos , Antitireóideos/uso terapêutico , Asma/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Feminino , Humanos , Hipertireoidismo/tratamento farmacológico , Antagonistas de Leucotrienos/efeitos adversos , Antagonistas de Leucotrienos/uso terapêutico , Troca Materno-Fetal , Metimazol/uso terapêutico , Êmese Gravídica/tratamento farmacológico , Ondansetron/uso terapêutico , Gravidez , Propiltiouracila/uso terapêutico , Teratogênios
4.
Artigo em Inglês | MEDLINE | ID: mdl-30863037

RESUMO

Introduction: This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting ß2-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT). Methods: Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database. MITT was defined as subjects with ≥1 overlapping days' supply of three COPD medications (ICS, LABA, and LAMA). Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up. In addition, analyses were stratified by number of inhalers. Results: In total, 14,635 MITT users were identified (mean age, 62 years). Mean PDC for MITT at 12 months was 0.37%. Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively. The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT. Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up. Conclusion: Patients with COPD had low adherence to and persistence with MITT in a real-world setting. Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT. Reducing the number of inhalers may improve overall adherence to intended triple therapy.


Assuntos
Corticosteroides/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Adesão à Medicação , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/efeitos adversos , Agonistas Adrenérgicos beta/efeitos adversos , Adulto , Idoso , Broncodilatadores/efeitos adversos , Bases de Dados Factuais , Combinação de Medicamentos , Feminino , Humanos , Seguro Saúde , Estudos Longitudinais , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
5.
Obstet Gynecol Surv ; 74(1): 50-55, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30648727

RESUMO

Importance: Preterm delivery represents an important cause of infant morbidity and mortality. Various tocolytics have been studied with the objective of stopping preterm labor, increasing gestational age at delivery, and preventing complications related to preterm birth. Objective: This review aims to summarize the major classes of tocolytics and review the evidence regarding use of each. Evidence Acquisition: A PubMed search of the following terms was performed to gather relevant data: "tocolytic," "preterm labor," "preterm delivery," "PPROM," "magnesium," "indomethacin," "nifedipine," and "betamimetics." Results: The benefits and risks of nonsteroid anti-inflammatory drugs, calcium channel blockers, magnesium, and betamimetics are reviewed. Calcium channel blockers afford superior outcomes in terms of prolonging gestation and decreasing neonatal morbidity and mortality with the fewest adverse effects. Conclusions and Relevance: Tocolytics, particularly calcium channel blockers, may provide benefit to pregnant women and their infants. Their use should be tailored to the particular clinical circumstances of the patient and used in conjunction with other management strategies (e.g., administration of corticosteroids for fetal lung maturation or magnesium for neuroprotection and transfer to a tertiary medical center). Further research and professional guidelines are needed on optimal use of these agents.


Assuntos
Trabalho de Parto Prematuro/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Tocólise/métodos , Tocolíticos/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Ruptura Prematura de Membranas Fetais/tratamento farmacológico , Idade Gestacional , Humanos , Gravidez , Tocolíticos/efeitos adversos
6.
Mov Disord ; 33(9): 1465-1471, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30311974

RESUMO

BACKGROUND: ß2-adrenoreceptors have recently been identified as regulators of the α-synuclein gene, which is implicated in the pathogenesis of Parkinson's disease. OBJECTIVE: The objectives of this study were to assess the association between use of ß2-agonists and ß-antagonists and the risk of developing PD. METHODS: We conducted a nested case-control study in a cohort of 1,762,164 adults without a diagnosis of PD. They were identified on January, 1, 2004, from the electronic medical records of the largest health care provider in Israel. Participants were followed up until June 30, 2017, for the occurrence of PD. Ten randomly selected controls were matched to each case of PD on age, sex, ethnic group, and duration of follow-up. RESULTS: During follow-up 11,314 patients were newly diagnosed with PD and were matched with 113,140 controls. An increased risk of PD was seen with the use of nonselective ß-antagonists (RR, 2.04 [1.90-2.20]) but not with the use of selective ß1-antagonists (RR, 1.00 [0.95-1.05]). Use of ß2-agonists was associated with reduced risk of PD (RR, 0.89 [0.82-0.96] for short-acting; RR, 0.84 [0.76-0.93] for long-acting; and RR, 0.49 [0.25-0.92] for ultra-long-acting ß2-agonists). In an analysis of individual drugs, propranolol and salbutamol were significantly associated with PD risk, even when these drugs were ascertained 5 years prior to the index date, compared with nonusers (RR, 1.31 [1.08-1.58] and 1.89 {1.53-2.33]) in patients who filled <6 and ≥6 propranolol prescriptions, respectively; the corresponding RRs for salbutamol were 0.95 (0.83-1.08) and 0.65 (0.45-0.94), respectively. CONCLUSIONS: Use of propranolol appears to be associated with an increased risk of PD, whereas use of ß2-agonists is associated with a decreased risk of PD. © 2018 International Parkinson and Movement Disorder Society.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Doença de Parkinson/epidemiologia , Doença de Parkinson/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
7.
Bull Exp Biol Med ; 165(5): 606-609, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30225718

RESUMO

The contractile function of the heart was studied in adult frogs Rana temporaria under the influence of a toxic dose of isoprenaline under conditions of natural sinoatrial rhythm and during heart pacing. The dynamics of ventricular pressure was recorded with a Prucka MacLab 2000 instrument via a catheter introduced into the ventricle through the ventricular wall. Reduced (p<0.05) parameters of the pump function (HR, maximum ventricular systolic pressure, isovolumic indices dP/dtmax and dP/dtmin) and lengthening of QRS complex and QT interval on ECG attested to impairment of contractile function and electrical processes after exposure to isoprenaline. Electrical stimulation of the right atrium improved myocardial contractility and ECG parameters after the administration of isoprenaline.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Ventrículos do Coração/efeitos dos fármacos , Isoproterenol/efeitos adversos , Contração Miocárdica/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos , Animais , Cateteres Cardíacos , Estimulação Elétrica , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Rana temporaria , Nó Sinoatrial/efeitos dos fármacos , Função Ventricular/efeitos dos fármacos
8.
PLoS One ; 13(9): e0203377, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30188953

RESUMO

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at a higher risk of many types of cancer. However, specific investigation of the risk of prostate cancer and the influence of COPD pharmacotherapy in patients with COPD is lacking. This study investigated the risk and influence of COPD pharmacotherapy on risk of prostate cancer in patients with COPD. METHODS: This retrospective cohort study used data from Taiwan's Longitudinal Health Insurance Database 2005 (LHID2005). The study cohort comprised COPD patients who received treatment between 2004 and 2008, and who were identified from the LHID2005. The control cohort comprised patients without COPD and was matched to the study cohort by age and sex. Two-stage propensity score calibration with the National Health Interview Survey 2005 was performed to obtain the missing confounders of smoking, alcohol drinking, and body mass index in the LHID. The hazard ratio (HR) and adjusted HR were estimated. Moreover, the influence of inhaled medications and other related medication on the risk of prostate cancer was analyzed by Cox proportional hazard regression. RESULTS: The COPD cohort comprised 12,774 patients, and the control cohort comprised 38,322 patients (1:3). The incidence of prostate cancer was 633 per 100,000 person-years in the COPD cohort and 361 per 100,000 person-years in the control cohort. The propensity score calibration-adjusted HR was 1.62 (95% CI, 1.40-1.87, p < 0.001) in the COPD cohort. Further analysis revealed that the adjusted HR for the risk of prostate cancer was 1.61 (95% CI, 1.19-2.16, p = 0.002) in patients with COPD who used short-acting muscarinic antagonists (SAMAs) and 1.89 (95% CI, 1.40-2.54, p < 0.001) in patients with COPD who used short-acting beta-agonists (SABAs). COPD patients had lower risk of prostate cancer when using statin (HR = 0.63, 95% CI, 0.45-0.89, p = 0.010) or aspirin (HR = 0.55, 95% CI, 0.35-0.85, p = 0.008). CONCLUSION: Patients with COPD are at a higher risk of prostate cancer, particularly those using SAMAs or SABAs. This finding suggests that inflammation control may be an effective strategy for decreasing the risk of prostate cancer.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Aspirina/efeitos adversos , Bases de Dados Factuais , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Antagonistas Muscarínicos/efeitos adversos , Neoplasias da Próstata , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Agonistas Adrenérgicos beta/administração & dosagem , Idoso , Aspirina/administração & dosagem , Estudos Transversais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/epidemiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco
9.
J Cardiovasc Electrophysiol ; 29(12): 1635-1640, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30192033

RESUMO

BACKGROUND: Electrophysiology study (EPS) is an important part of the diagnosis and workup for supraventricular tachycardia (SVT). Provocative medications are used to induce arrhythmias, when they are not inducible at baseline. The most common medication is the ß1-specific agonist, isoproterenol, but recent price increases have resulted in a shift toward the nonspecific agonist, epinephrine. OBJECTIVE: We hypothesize that isoproterenol is a better induction agent for SVT during EPS than epinephrine. METHODS: We created a retrospective cohort of 131 patients, who underwent EPS and required medication infusion with either isoproterenol or epinephrine for SVT induction. The primary outcome was arrhythmia induction. RESULTS: Successful induction was achieved in 71% of isoproterenol cases and 53% of epinephrine cases (P = 0.020). Isoproterenol was significantly better than epinephrine for SVT induction during EPS (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.14-4.85; P = 0.021). There was no difference in baseline variables or complications between the two groups. Other variables associated with successful arrhythmia induction included a longer procedure duration and atrioventricular nodal re-entry tachycardia as the clinical arrhythmia. In a multivariable model, isoproterenol remained significantly associated with successful induction (OR, 2.57; 95% CI, 1.002-6.59; P = 0.05). CONCLUSIONS: Isoproterenol was significantly better than epinephrine for SVT arrhythmia induction. However, epinephrine was safe and successfully induced arrhythmias in the majority of patients who received it. Furthermore, when atropine was added in epinephrine-refractory cases, in a post hoc analysis there was no difference in arrhythmia induction between medications. Cost savings could thus be significant without compromising safety.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Técnicas Eletrofisiológicas Cardíacas/métodos , Epinefrina/efeitos adversos , Isoproterenol/efeitos adversos , Taquicardia Supraventricular/induzido quimicamente , Taquicardia Supraventricular/fisiopatologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Am Heart J ; 204: 196-201, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30100052

RESUMO

Management of acute decompensated heart failure patients presenting with cardiogenic shock (CS) is not straightforward, as few data are available from clinical trials. Stabilization before left ventricle assist device (LVAD) or heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD implant or HTx in critical status have worse outcomes. This was a multicenter phase II study with a Simon 2-stage design, including 24 consecutive patients treated with low-moderate epinephrine doses, whose refractory CS prompted implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded with peripheral venoarterial extracorporeal membrane oxygenation. At admission, patients had severe left ventricular dysfunction and overt CS, 7 patients could be managed only with inotropic therapy, and 16 patients were transitioned to IABP and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median duration of epinephrine therapy was 7 days (interquartile range 6-15), and the median dose was 0.08 µg/kg/min (interquartile range 0.05-0.1); 21 patients (87.5%) survived at 60 days (primary outcome); among them, 13 (61.9%) underwent LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical treatment, indicating that early and intensive treatment of CS in chronic advanced heart failure patients with low-dose epinephrine and timely short-term mechanical circulatory support leads to satisfactory outcomes.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Epinefrina/uso terapêutico , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/complicações , Balão Intra-Aórtico , Choque Cardiogênico/terapia , Vasoconstritores/uso terapêutico , Agonistas Adrenérgicos beta/efeitos adversos , Idoso , Algoritmos , Terapia Combinada , Epinefrina/efeitos adversos , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Cardiogênico/etiologia , Resultado do Tratamento , Vasoconstritores/efeitos adversos
12.
N Engl J Med ; 378(26): 2497-2505, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29949492

RESUMO

BACKGROUND: Safety concerns regarding long-acting ß2-agonists (LABAs) in asthma management were initially identified in a large postmarketing trial in which the risk of death was increased. In 2010, the Food and Drug Administration (FDA) mandated that the four companies marketing LABAs for asthma perform prospective, randomized, controlled trials comparing the safety of combination therapy with a LABA plus an inhaled glucocorticoid with that of an inhaled glucocorticoid alone in adolescents (12 to 17 years of age) and adults. In conjunction with the FDA, the manufacturers harmonized their trial methods to allow an independent joint oversight committee to provide a final combined analysis of the four trials. METHODS: As members of the joint oversight committee, we performed a combined analysis of the four trials comparing an inhaled glucocorticoid plus a LABA (combination therapy) with an inhaled glucocorticoid alone. The primary outcome was a composite of asthma-related intubation or death. Post hoc secondary outcomes included serious asthma-related events and asthma exacerbations. RESULTS: Among the 36,010 patients in the intention-to-treat study, there were three asthma-related intubations (two in the inhaled-glucocorticoid group and one in the combination-therapy group) and two asthma-related deaths (both in the combination-therapy group) in 4 patients. In the secondary analysis of serious asthma-related events (a composite of hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the combination-therapy group had at least one composite event (relative risk in the combination-therapy group, 1.09; 95% confidence interval [CI], 0.83 to 1.43; P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in the combination-therapy group (9.8%) had at least one asthma exacerbation (relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001). CONCLUSIONS: Combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations.


Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Glucocorticoides/administração & dosagem , Administração por Inalação , Adolescente , Agonistas Adrenérgicos beta/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/efeitos adversos , Criança , Preparações de Ação Retardada , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Feminino , Glucocorticoides/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
13.
N Engl J Med ; 378(18): 1671-1680, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29668352

RESUMO

BACKGROUND: The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting ß2-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid-LABA or LAMA-LABA), are uncertain. METHODS: In this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 µg, umeclidinium (a LAMA) at a dose of 62.5 µg, and vilanterol (a LABA) at a dose of 25 µg (triple therapy) with fluticasone furoate-vilanterol (at doses of 100 µg and 25 µg, respectively) and umeclidinium-vilanterol (at doses of 62.5 µg and 25 µg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment. RESULTS: The rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate-vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium-vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium-vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium-vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium-vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001). CONCLUSIONS: Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate-vilanterol or umeclidinium-vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium-vilanterol. (Funded by GlaxoSmithKline; IMPACT ClinicalTrials.gov number, NCT02164513 .).


Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Broncodilatadores/administração & dosagem , Glucocorticoides/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Agonistas Adrenérgicos beta/efeitos adversos , Adulto , Idoso , Androstadienos/administração & dosagem , Álcoois Benzílicos/administração & dosagem , Broncodilatadores/efeitos adversos , Clorobenzenos/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Dispneia/tratamento farmacológico , Dispneia/etiologia , Feminino , Glucocorticoides/efeitos adversos , Hospitalização/estatística & dados numéricos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/complicações , Qualidade de Vida , Quinuclidinas/administração & dosagem
14.
Can J Physiol Pharmacol ; 96(7): 639-646, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29633627

RESUMO

Catecholamines are involved in the regulation of a wide variety of vital functions. The ß-adrenergic receptor (ß-AR) - adenylyl cyclase system has been identified early in embryogenesis before the heart has received adrenergic innervation. The structure of ß-receptors in the immature myocardium is similar to that in adults; there are, however, significant quantitative developmental changes in the inotropic and chronotropic responsiveness. Information on the toxic effect of the ß-AR agonists in the immature heart is surprisingly scarce, even though these agents are used in clinical practice both during pregnancy and in early postnatal development. Large doses of ß-AR agonists induce malformations of the cardiovascular system; the type of change depends upon the time at which the ß-AR agonist was administered during embryogenesis. During postnatal ontogeny, the cardiotoxicity of ß-AR agonists increased from birth to adulthood. It seems likely that despite interspecies differences, developmental changes in the cardiac sensitivity to ß-AR agonists may exist in all mammals, depending on the degree of maturation of the system involved in ß-adrenergic signaling. All the existing data draw attention to the possible harmful consequences of the clinical use of ß-AR agonists during early phases of cardiac development. Late effects of the early disturbances of the cardiac muscle cannot be excluded.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Catecolaminas/efeitos adversos , Coração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tocolíticos/efeitos adversos , Adenilil Ciclases/metabolismo , Animais , Cardiotoxicidade/etiologia , Feminino , Coração/embriologia , Humanos , Gravidez , Receptores Adrenérgicos beta/metabolismo
15.
Rev. esp. enferm. dig ; 110(4): 254-256, abr. 2018. ilus
Artigo em Espanhol | IBECS | ID: ibc-174602

RESUMO

This article is the first description of a spontaneous hepatic rupture in a young bodybuilder with a history of clenbuterol and ephedrine alkaloid use. The patient presented with a sudden mid-epigastric pain and vomiting. Hemoglobin levels decreased a few hours later and a computed tomography scan was performed which revealed a rupture of the right liver capsule and hemoperitoneum. Two attempts at transarterial embolization did not control the bleeding and a right hemihepatectomy was performed. The pathological report identified a hepatic adenoma, a capsular tear and diffuse peliosis hepatis. The patient was discharged in a good condition after eleven days. Spontaneous hepatic ruptures are rare and life-threatening and are usually described in association with tumors, connective tissue diseases and gestosis. This article is a review of the available literature with regard to this condition, with a focus on its relation to peliosis hepatis and banned substance used by body image fanatics. The present case highlights the challenging diagnosis of this potentially fatal liver complication in a healthy appearing male, the risk associated with the online trade of performance enhancing drugs and its relation with peliosis hepatis


No disponible


Assuntos
Humanos , Masculino , Adulto , Fígado/lesões , Peliose Hepática/induzido quimicamente , Ruptura/etiologia , Substâncias para Melhoria do Desempenho/efeitos adversos , Agonistas Adrenérgicos beta/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Clembuterol/efeitos adversos , Efedrina/efeitos adversos , Fígado/cirurgia , Peliose Hepática/complicações , Ruptura/cirurgia , Resultado do Tratamento
19.
J Toxicol Environ Health A ; 81(7): 194-201, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29405861

RESUMO

The occurrence of ractopamine (RAC) hydrochloride in water bodies is of significant concern due to its ecological impacts and toxicity to humans. RAC hydrochloride is a ß-adrenergic agonist drug used as a feed additive to (1) improve feed efficiency, (2) rate of weight gain, and (3) increase carcass leanness in animals raised for their meat. This drug is excreted by animals in urine and introduced into the environment affecting nontarget organisms including fish. In wastewater released from farms, RAC concentrations were detected from 0.124 µg/L to 30.1 µg/L, and in levels ranging from 1.3 × 10-5 to 5.4 × 10-4 µg/L in watersheds. The aim of this study was to examine the effects of exposure to RAC at 0.1, 0.2, 0.85, 8.5, or 85 µg/L dissolved in water on behavior and oxidative status in adult zebrafish. At 0.85 µg/L, RAC treatment increased exploratory behavior of zebrafish; while at 8.5 µg/L, decreased locomotor and exploratory activities were noted. With respect to oxidative stress biomarkers, results showed that RAC at 0.2 µg/L induced lipid peroxidation and elevated total thiol content in zebrafish brain. All drug tested concentrations produced a fall in nonprotein thiol content. Finally, RAC at 0.85, 8.5, or 85 µg/L increased catalase enzyme activity. Our results demonstrated that the exposure to RAC induced behavioral alterations and oxidative stress in zebrafish.


Assuntos
Comportamento Exploratório/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenetilaminas/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , Peixe-Zebra/fisiologia , Agonistas Adrenérgicos beta/efeitos adversos , Animais , Suplementos Nutricionais/efeitos adversos , Relação Dose-Resposta a Droga , Aditivos Alimentares/efeitos adversos
20.
PLoS One ; 13(2): e0192322, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466442

RESUMO

AIMS: In contrast to the membrane bound adenylyl cyclases, the soluble adenylyl cyclase (sAC) is activated by bicarbonate and divalent ions including calcium. sAC is located in the cytosol, nuclei and mitochondria of several tissues including cardiac muscle. However, its role in cardiac pathology is poorly understood. Here we investigate whether sAC is involved in hypertrophic growth using two different model systems. METHODS AND RESULTS: In isolated adult rat cardiomyocytes hypertrophy was induced by 24 h ß1-adrenoceptor stimulation using isoprenaline (ISO) and a ß2-adrenoceptor antagonist (ICI118,551). To monitor hypertrophy cell size along with RNA/DNA- and protein/DNA ratios as well as the expression level of α-skeletal actin were analyzed. sAC activity was suppressed either by treatment with its specific inhibitor KH7 or by knockdown. Both pharmacological inhibition and knockdown blunted hypertrophic growth and reduced expression levels of α-skeletal actin in ISO/ICI treated rat cardiomyocytes. To analyze the underlying cellular mechanism expression levels of phosphorylated CREB, B-Raf and Erk1/2 were examined by western blot. The results suggest the involvement of B-Raf, but not of Erk or CREB in the pro-hypertrophic action of sAC. In wild type and sAC knockout mice pressure overload was induced by transverse aortic constriction. Hemodynamics, heart weight and the expression level of the atrial natriuretic peptide were analyzed. In accordance, transverse aortic constriction failed to induce hypertrophy in sAC knockout mice. Mechanistic analysis revealed a potential role of Erk1/2 in TAC-induced hypertrophy. CONCLUSION: Soluble adenylyl cyclase might be a new pivotal player in the cardiac hypertrophic response either to long-term ß1-adrenoceptor stimulation or to pressure overload.


Assuntos
Adenilil Ciclases/metabolismo , Agonistas Adrenérgicos beta/efeitos adversos , Cardiomegalia/enzimologia , Isoproterenol/efeitos adversos , Animais , Cardiomegalia/induzido quimicamente , Camundongos , Pressão , Ratos
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