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1.
Anesth Prog ; 70(2): 58-64, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37379094

RESUMO

OBJECTIVE: This study investigated the involvement of α1- and ß2-adrenergic receptors in skeletal muscle blood flow changes during variations in ETCO2. METHODS: Forty Japanese White rabbits anesthetized with isoflurane were randomly allocated to 1 of 5 groups: phentolamine, metaproterenol, phenylephrine, butoxamine, and atropine. Heart rate (HR), systolic blood pressure (SBP), common carotid artery blood flow (CCBF), masseter muscle tissue blood flow (MBF), and quadriceps muscle tissue blood flow (QBF) were recorded and analyzed at 3 periods: (1) baseline, (2) during hypercapnia (phentolamine and metaproterenol groups) or hypocapnia (phenylephrine, butoxamine, and atropine groups), and (3) during or after receiving vasoactive agents. RESULTS: MBF and QBF decreased during hypercapnia. The decrease in MBF was smaller than that in QBF. SBP and CCBF increased, while HR decreased. Both MBF and QBF recovered to their baseline levels after phentolamine administration. MBF became greater than its baseline level, while QBF did not fully recover after metaproterenol administration. MBF and QBF increased during hypocapnia. The increase rate in MBF was larger than that in QBF. HR, SBP, and CCBF did not change. Both MBF and QBF decreased to ∼90% to 95% of their baseline levels after phenylephrine or butoxamine administration. Atropine showed no effects on MBF and QBF. CONCLUSION: These results suggest the skeletal muscle blood flow changes observed during hypercapnia and hypocapnia may mainly involve α1-adrenergic but not ß2-adrenergic receptor activity.


Assuntos
Hipercapnia , Hipocapnia , Animais , Coelhos , Fentolamina/farmacologia , Receptores Adrenérgicos beta , Butoxamina , Pressão Sanguínea , Músculo Esquelético , Fenilefrina/farmacologia , Metaproterenol , Derivados da Atropina , Fluxo Sanguíneo Regional
2.
Terminologia | DeCS - Descritores em Ciências da Saúde | ID: 010100

RESUMO

A beta-2 adrenergic agonist used in the treatment of ASTHMA and BRONCHIAL SPASM.


Un agonista adrenérgico beta utilizado en el tratamiento del ASMA y en el ESPASMO BRONQUIAL.


Agonista beta-2 adrenérgico utilizado no tratamento da ASMA e de ESPASMO BRÔNQUICO.

3.
Med Hypotheses ; 144: 110027, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758873

RESUMO

There currently is no specific antiviral drug or a vaccine for SARS-CoV-2/COVID-19 infections; now exceeding 10,300,000 infections worldwide. In the absence of animal models to test drugs, we need to find molecular explanations for any unforeseen peculiarities in clinical data, especially the recent reports describing an unexpected asthma paradox. Asthma is considered a high medical risk factor for susceptibility to SARS-CoV-2/COVID-19 infection, yet asthma is not on the list of top 10 chronic health problems suffered by people who died from SARS-CoV-2/COVID-19. Resolving this paradox requires looking beyond the binary model of a viral receptor-binding domain (RBD) attaching to the ACE-2 receptor. A NCBI pBlast analysis revealed that the SARS-CoV-2 surface spike protein contains key two calcium-dependent fusion domains that are almost identical to those that were recently discovered SARS-CoV-1. These viral calcium-dependent binding domains can facilitate membrane fusion only after cleavage by the host surface protease TMPRSS2. Importantly, TMPRSS2 also requires calcium for its SRCR (scavenger receptor cysteine-rich) domain and itsLDLRA(LDL receptor class A) domain. Thus, the presence of EDTA excipients in nebulized ß2-agonist medicines can disrupt SARS-CoV-2/COVID-19 infection and can explain the asthma paradox. This model validates repurposing EDTA in nebulizer solutions from a passive excipient to an active drug for treating COVID-19 infections. Repurposed EDTA delivery to respiratory tissues at an initial target dose of 2.4 mg per aerosol treatment is readily achievable with standard nebulizer and mechanical ventilator equipment. EDTA warrants further investigation as a potential treatment for SARS-CoV-2/COVID-19 in consideration of the new calcium requirements for virus infection and the regular presence of EDTA excipients in common asthma medications such as Metaproterenol. Finally, the natural history of Coronavirus diseases and further analysis of the fusion loop homologies between the Betacorona SARS-CoV-2 virus and the less pathogenic Alphacorona HC0V-229E virus suggest how to engineer a hybrid virus suitable for an attenuated alpha-beta SARS-CoV-2/COVID-19 vaccine. Thus, replacing SARS-CoV-2 fusion loops (amino acids 816-855) with the less pathogenic HCoV-229E fusion loop (amino acids 923-982) may provide antigenicity of COVID-19, but limit the pathogenicity to the level of HCoV-229E.


Assuntos
Asma/complicações , Asma/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , Reposicionamento de Medicamentos , Ácido Edético/uso terapêutico , Antivirais/uso terapêutico , Broncodilatadores/uso terapêutico , Vacinas contra COVID-19 , Cálcio/química , Suscetibilidade a Doenças , Excipientes/uso terapêutico , Humanos , Metaproterenol/uso terapêutico , Modelos Teóricos , Nebulizadores e Vaporizadores , Prevalência , Receptores de LDL/química , Fatores de Risco , Serina Endopeptidases/metabolismo
4.
Eur J Pharmacol ; 882: 173304, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32592771

RESUMO

Recently, the ß2-adrenoceptor agonist terbutaline was shown to have α1-adrenolytic activity in mouse isolated pulmonary arteries in vitro and to lower pulmonary artery pressure in anaesthetised mice. The aim of our study was to determine the α1-adrenoceptor antagonist activity of terbutaline and its structurally close resorcinol, orciprenaline, in rat isolated small mesenteric arteries set up for myography. Their α1-adrenoceptor antagonist potency was then compared with their potency as ß2-adrenoceptor agonists. Concentration-response curves to methoxamine were competitively antagonised by terbutaline (30-300 µM) or orciprenaline (30-300 µM) with a pKB of 4.70 ± 0.09 or 4.79 ± 0.17, respectively. Both terbutaline and orciprenaline fulfilled the criteria for simple, silent competitive antagonism. Terbutaline (30-300 µM) had no effect on endothelin-1 concentration-contraction curves. Our findings suggest that after oral dosing of terbutaline, the maximum plasma levels would NOT reach levels to show α1-adrenoceptor antagonist activity. In conclusion, our work has provided additional quantitative evidence that terbutaline and orciprenaline are weak competitive α1-adrenoceptor antagonists, but this additional property is probably not therapeutically important in the clinical treatment of asthma or pulmonary artery hypertension with these more potent ß2-adrenoceptor agonists.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Broncodilatadores/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Metaproterenol/farmacologia , Terbutalina/farmacologia , Animais , Masculino , Artérias Mesentéricas/fisiologia , Ratos Sprague-Dawley
7.
Luminescence ; 34(1): 77-83, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30536899

RESUMO

Orciprenaline sulphate (ORP) is a direct-acting sympathomimetic with mainly beta-adrenoceptor stimulant activity. It is used as a bronchodilator in the management of reversible airway obstruction. For the first time, a rapid highly sensitive spectrofluorimetric method is described that is relied on measuring the fluorescence spectra of ORP at acidic pH and without addition of any chemical reagents. The relative fluorescence intensity was measured at 310 nm and after excitation at 224 nm. ORP native fluorescence was calibrated in both water and acetonitrile as diluting solvents. The method was designed to estimate the drug in miscellaneous matrices with high accuracy and precision. Linear ranges of calibration curves were 30.0-400.0 ng/ml and 10.0-240.0 ng/ml in water and acetonitrile, respectively. The detection limits were calculated and reached as low as 3.3 and 3.1 ng/ml, respectively, representing the ultra-sensitivity of the proposed method. This result permitted application of this method for spiked human plasma and urine and was used as a preliminary investigation with good percentage recovery (89.4-106.8%). The application was further extended to analyse ORP in its pharmaceutical formulations. The method was validated in compliance with International Council of Harmonization (ICH) Guidelines.


Assuntos
Metaproterenol/análise , Espectrometria de Fluorescência/métodos , Acetonitrilas/química , Broncodilatadores/análise , Broncodilatadores/sangue , Broncodilatadores/urina , Calibragem , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Metaproterenol/sangue , Metaproterenol/urina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Solventes/química
8.
Cochrane Database Syst Rev ; 1: CD001284, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28076656

RESUMO

BACKGROUND: Inhaled short-acting anticholinergics (SAAC) and short-acting beta2-agonists (SABA) are effective therapies for adult patients with acute asthma who present to the emergency department (ED). It is unclear, however, whether the combination of SAAC and SABA treatment is more effective in reducing hospitalisations compared to treatment with SABA alone. OBJECTIVES: To conduct an up-to-date systematic search and meta-analysis on the effectiveness of combined inhaled therapy (SAAC + SABA agents) vs. SABA alone to reduce hospitalisations in adult patients presenting to the ED with an exacerbation of asthma. SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, SCOPUS, LILACS, ProQuest Dissertations & Theses Global and evidence-based medicine (EBM) databases using controlled vocabulary, natural language terms, and a variety of specific and general terms for inhaled SAAC and SABA drugs. The search spanned from 1946 to July 2015. The Cochrane Airways Group provided search results from the Cochrane Airways Group Register of Trials which was most recently conducted in July 2016. An extensive search of the grey literature was completed to identify any other potentially relevant studies. SELECTION CRITERIA: Included studies were randomised or controlled clinical trials comparing the effectiveness of combined inhaled therapy (SAAC and SABA) to SABA treatment alone to prevent hospitalisations in adults with acute asthma in the emergency department. Two independent review authors assessed studies for inclusion using pre-determined criteria. DATA COLLECTION AND ANALYSIS: For dichotomous outcomes, we calculated individual and pooled statistics as risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) using a random-effects model and reporting heterogeneity (I²). For continuous outcomes, we reported individual trial results using mean differences (MD) and pooled results as weighted mean differences (WMD) or standardised mean differences (SMD) with 95% CIs using a random-effects model. MAIN RESULTS: We included 23 studies that involved a total of 2724 enrolled participants. Most studies were rated at unclear or high risk of bias.Overall, participants receiving combination inhaled therapy were less likely to be hospitalised (RR 0.72, 95% CI 0.59 to 0.87; participants = 2120; studies = 16; I² = 12%; moderate quality of evidence). An estimated 65 fewer patients per 1000 would require hospitalisation after receiving combination therapy (95% 30 to 95), compared to 231 per 1000 patients receiving SABA alone. Although combination inhaled therapy was more effective than SABA treatment alone in reducing hospitalisation in participants with severe asthma exacerbations, this was not found for participants with mild or moderate exacerbations (test for difference between subgroups P = 0.02).Participants receiving combination therapy were more likely to experience improved forced expiratory volume in one second (FEV1) (MD 0.25 L, 95% CI 0.02 to 0.48; participants = 687; studies = 6; I² = 70%; low quality of evidence), peak expiratory flow (PEF) (MD 36.58 L/min, 95% CI 23.07 to 50.09; participants = 1056; studies = 12; I² = 25%; very low quality of evidence), increased percent change in PEF from baseline (MD 24.88, 95% CI 14.83 to 34.93; participants = 551; studies = 7; I² = 23%; moderate quality of evidence), and were less likely to return to the ED for additional care (RR 0.80, 95% CI 0.66 to 0.98; participants = 1180; studies = 5; I² = 0%; moderate quality of evidence) than participants receiving SABA alone.Participants receiving combination inhaled therapy were more likely to experience adverse events than those treated with SABA agents alone (OR 2.03, 95% CI 1.28 to 3.20; participants = 1392; studies = 11; I² = 14%; moderate quality of evidence). Among patients receiving combination therapy, 103 per 1000 were likely to report adverse events (95% 31 to 195 more) compared to 131 per 1000 patients receiving SABA alone. AUTHORS' CONCLUSIONS: Overall, combination inhaled therapy with SAAC and SABA reduced hospitalisation and improved pulmonary function in adults presenting to the ED with acute asthma. In particular, combination inhaled therapy was more effective in preventing hospitalisation in adults with severe asthma exacerbations who are at increased risk of hospitalisation, compared to those with mild-moderate exacerbations, who were at a lower risk to be hospitalised. A single dose of combination therapy and multiple doses both showed reductions in the risk of hospitalisation among adults with acute asthma. However, adults receiving combination therapy were more likely to experience adverse events, such as tremor, agitation, and palpitations, compared to patients receiving SABA alone.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Antagonistas Colinérgicos/uso terapêutico , Albuterol/uso terapêutico , Atropina/uso terapêutico , Quimioterapia Combinada , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Ipratrópio/uso terapêutico , Levalbuterol/uso terapêutico , Metaproterenol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Derivados da Escopolamina/uso terapêutico
9.
Indian Heart J ; 68 Suppl 2: S194-S197, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27751287

RESUMO

Cardiac rhythm abnormalities have been uncommonly observed in dengue fever and most of them have been reported in children. We discuss a 30-year-old female with dengue fever, who presented with repeated symptomatic episodes of high degree atrioventricular block with ventricular asystole, which responded to intravenous atropine and oral orciprenaline without recurrence on 6 months follow-up.


Assuntos
Bloqueio Atrioventricular/etiologia , Atropina/administração & dosagem , Dengue/complicações , Parada Cardíaca/etiologia , Ventrículos do Coração/fisiopatologia , Metaproterenol/administração & dosagem , Administração Oral , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Adulto , Antiarrítmicos/administração & dosagem , Bloqueio Atrioventricular/tratamento farmacológico , Bloqueio Atrioventricular/fisiopatologia , Quimioterapia Combinada , Eletrocardiografia , Feminino , Seguimentos , Parada Cardíaca/tratamento farmacológico , Parada Cardíaca/fisiopatologia , Humanos , Injeções Intravenosas
10.
Can J Cardiol ; 32(12): 1577.e5-1577.e7, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27032887

RESUMO

We present a case of a symptomatic patient with Brugada syndrome, who had sustained right ventricular outflow tract tachycardia after pronounced exercise-induced ST segment elevation in V1 and V2. In electrophysiological study he developed right ventricular outflow tract tachycardia provoked by combined infusion of ajmaline and orciprenaline. After ablation no further arrhythmia was provoked by pharmacological stimulation.


Assuntos
Síndrome de Brugada , Ablação por Cateter/métodos , Taquicardia Ventricular , Ajmalina/administração & dosagem , Ajmalina/efeitos adversos , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatologia , Síndrome de Brugada/terapia , Eletrocardiografia/métodos , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Metaproterenol/administração & dosagem , Metaproterenol/efeitos adversos , Pessoa de Meia-Idade , Estimulação Química , Taquicardia Ventricular/induzido quimicamente , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/prevenção & controle , Resultado do Tratamento
11.
Toxicol Appl Pharmacol ; 312: 53-60, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26627004

RESUMO

Conventional circulating biomarkers of cardiac and skeletal muscle (SKM) toxicity lack specificity and/or have a short half-life. MicroRNAs (miRNAs) are currently being assessed as biomarkers of tissue injury based on their long half-life in blood and selective expression in certain tissues. To assess the utility of miRNAs as biomarkers of cardiac and SKM injury, male Sprague-Dawley rats received a single dose of isoproterenol (ISO); metaproterenol (MET); allylamine (AAM); mitoxantrone (MIT); acetaminophen (APAP) or vehicle. Blood and tissues were collected from rats in each group at 4, 24 and 48h. ISO, MET, and AAM induced cardiac and SKM lesions and APAP induced liver specific lesions. There was no evidence of tissue injury with MIT by histopathology. Serum levels of candidate miRNAs were compared to conventional serum biomarkers of SKM/cardiac toxicity. Increases in heart specific miR-208 only occurred in rats with cardiac lesions alone and were increased for a longer duration than cardiac troponin and FABP3 (cardiac biomarkers). ISO, MET and AAM induced increases in MyL3 and skeletal muscle troponin (sTnl) (SKM biomarkers). MIT induced large increases in sTnl indicative of SKM toxicity, but sTnl levels were also increased in APAP-treated rats that lacked SKM toxicity. Serum levels of miR-133a/b (enriched in cardiac and SKM) increased following ISO, MET, AAM and MIT treatments but were absent in APAP-treated rats. Our results suggest that miR-133a/b are sensitive and specific markers of SKM and cardiac toxicity and that miR-208 used in combination with miR-133a/b can be used to differentiate cardiac from SKM toxicity.


Assuntos
Biomarcadores/sangue , Coração/efeitos dos fármacos , MicroRNAs/sangue , Músculo Esquelético/efeitos dos fármacos , Acetaminofen/toxicidade , Alilamina/toxicidade , Animais , Isoproterenol/toxicidade , Masculino , Metaproterenol/toxicidade , Mitoxantrona/toxicidade , Ratos , Ratos Sprague-Dawley
12.
Europace ; 17(3): 489-94, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25349222

RESUMO

AIMS: Although sinus node modification by catheter ablation is an established therapy for the treatment of inappropriate sinus tachycardia, there is incomplete understanding of sinus node anatomy and function but also limited electroanatomical mapping data. Recently, an automatic, ultra high-resolution mapping system has been presented to accurately and quickly identify right atrial (RA) geometry and activation patterns but detailed assessment of sinus node activation has not been performed which was one aim of this study. Preclinical experiences are compared with previous sinus node mapping studies in animals and humans, and potential clinical implications for catheter ablation are discussed. METHODS AND RESULTS: In anaesthetized and ventilated 14 pigs, 30 endocardial and 2 eipcardial RA maps were generated using the Rhythmia™ mapping system without complications and earliest activation sites (EAS) and sinus break-out (SBO) were determined. At baseline, EAS and SBO were located anterior to the middle (n = 6) or lower third (n = 8) of the crista terminalis exhibiting a unicentric activation pattern in all cases. Conduction pathways were directed anterior, posterior, superior, or inferior with substantial inter-individual variation in direction, pathway distance, and conduction time. Orciprenaline, propranolol, or amiodarone shifted endocardial activation with considerable variation between animals with inconsistent patterns. Multicentric activation was found in one case after orciprenaline infusion. Sequential endocardial and epicardial high-density mapping of the RA was performed in two animals and showed a high congruence of the sinus node activation in the endo- and the epicardial map. CONCLUSION: Ultra high-density mapping allows fast, simple, and very detailed assessment of sinus node activation. Future studies are clearly needed to evaluate novel mapping and ablation strategies for an improved understanding of sinus node disease and better outcomes.


Assuntos
Função do Átrio Direito , Mapeamento Epicárdico/métodos , Nó Sinoatrial/fisiologia , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Amiodarona/farmacologia , Animais , Antiarrítmicos/farmacologia , Técnicas Eletrofisiológicas Cardíacas , Átrios do Coração/efeitos dos fármacos , Metaproterenol/farmacologia , Propranolol/farmacologia , Nó Sinoatrial/efeitos dos fármacos , Suínos
14.
Int J Cardiol ; 168(4): 4122-31, 2013 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-23920058

RESUMO

INTRODUCTION: Recurrences after pulmonary vein isolation (PVI) in patients (pts) with paroxysmal atrial fibrillation (AF) are mostly due to PV reconnection. The effect of adenosine, orciprenalin and their combination on left atrial PV conduction after PVI with a phased radiofrequency (RF) circular multielectrode ablation catheter (Pulmonary Vein Ablation Catheter, PVAC) was prospectively evaluated during a prolonged waiting time. In addition, it was assessed whether pharmacological reconnection characterizes veins requiring use of an irrigated catheter. METHODS AND RESULTS: In 116 consecutive pts [age 62 (IQR:52,68) years, 46% female], PVI was achieved with the PVAC alone in 114/116 (98%) pts and 461/464 (99%) veins after a median of 26 (IQR:22,32) applications delivering 1782 s (IQR:1518,2197) of RF. Mostly transient PV reconnections were observed in 40/116 (34%) pts and 57/464 (12%) PVs, a median of 44 (IQR:30,58) min after initial isolation. Adenosine, alone (43/57, 75%) or during orciprenalin infusion (7/57, 12%), unmasked residual conduction in the majority of veins (50/57, 88%). Additional PVAC applications less frequently achieved permanent isolation in veins showing reconnection compared to those that didn't (52/57, 91% vs. 404/407, 99%; P < .001). All PVs that could not be isolated with the PVAC were successfully treated with a standard irrigated catheter. CONCLUSIONS: After apparent PVI with the PVAC, drug-challenge after prolonged observation unmasked residual PV conduction in a significant number of pts, and adenosine was the most effective strategy. Drug-induced PV reconnection was difficult to treat with the PVAC. Whether this strategy improves clinical outcome of PVI with phased RF needs to be investigated.


Assuntos
Adenosina/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Metaproterenol/administração & dosagem , Veias Pulmonares/cirurgia , Idoso , Fibrilação Atrial/diagnóstico , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/patologia , Fatores de Tempo , Resultado do Tratamento
15.
Eur J Pharmacol ; 700(1-3): 2-12, 2013 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-23270716

RESUMO

We investigated the effects of α- and ß-adrenoceptor agonists on L-ascorbic acid-induced hepatocyte DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. The results showed that phenylephrine (10(-6) M) and metaproterenol (10(-6) M) alone did not induce hepatocyte DNA synthesis and proliferation. However, when combined with L-ascorbic acid (10(-6) M), these adrenoceptor agonists potentiated the hepatocyte DNA synthesis and proliferation induced by L-ascorbic acid. Then intracellular signal transduction mechanisms for the effects of phenylephrine and metaproterenol on L-ascorbic acid-induced hepatocyte mitogenesis were examined. Western blot analysis showed that phenylephrine and metaproterenol did not potentiate L-ascorbic acid-induced insulin-like growth factor I receptor tyrosine kinase phosphorylation. In contrast, they both significantly potentiated L-ascorbic acid-induced extracellular-signal regulated kinase-2 (ERK2) phosphorylation within 5 min. Moreover, cell-permeable second messenger analogs phorbol ester (10(-7) M) and 8-bromo cAMP (10(-7) M) mimicked the effects of phenylephrine and metaproterenol on L-ascorbic acid-induced ERK2 phosphorylation. The effects of these adrenoceptor agents were specifically antagonized by GF109203X and H-89, respectively. These results indicate that activation of ERK2 via protein kinas C and protein kinase A represents a mechanism for potentiation of L-ascorbic acid-induced hepatocyte DNA synthesis and proliferation in primary cultures of adult rat hepatocytes.


Assuntos
Ácido Ascórbico/farmacologia , DNA/biossíntese , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Transdução de Sinais/efeitos dos fármacos , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Sinergismo Farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hepatócitos/metabolismo , Masculino , Metaproterenol/farmacologia , Fenilefrina/farmacologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Receptor IGF Tipo 1/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo
16.
Rev Electron ; 37(11)nov. 2012.
Artigo em Espanhol | CUMED | ID: cum-52343

RESUMO

Una vez instalado por completo el trabajo de parto pretérmino, los recursos para inhibirlos son poco eficaces, de ahí que las acciones preventivas desempeñan un papel fundamental en las estrategias para reducir la frecuencia y el impacto desfavorable del nacimiento pretérmino en la salud infantil. Los medicamentos que interrumpen o detienen la contractilidad uterina, llamados agentes tocolíticos, solo son eficaces cuando se administran antes del completo establecimiento del trabajo de parto. La hidratación puede reducir la contractilidad mediante el aumento del flujo sanguíneo uterino y una disminución de la secreción pituitaria de la hormona antidiurética y la oxitocina. Los medicamentos empleados para tocolisis incluyen los agentes betamiméticos (ritodrina, la terbutalina y la orciprenalina), los que inhiben la síntesis de prostaglandinas (anti-inflamatorios no esteroideos, indometacina), los que modifican la transmisión nerviosa en la placa neuromuscular (el sulfato de magnesio), y los inhibidores de los canales del calcio (la nifedipina). El nifedipino es considerado el tocolítico de primera elección y el más eficaz en la prevención del parto pretérmino (AU)


Once preterm labor is completely set up, the resources to restrain it are slightly effective; consequently preventive measures play an important role in the strategies to reduce the frequency and unfavorable impact of a preterm birth in neonatal health. The drugs to interrupt or stop uterine contractility, known as tocolytic agents, are only effective when administered before the full establishment of the delivery labor. Hydration can reduce contractility by increasing uterine blood flow and decreasing pituitary secretion of the antidiuretic hormone and the oxytocin. Drugs used as tocolytic agents include beta mimetic agents (ritodrine, terbutaline and orciprenaline), the ones inhibiting prostaglandin synthesis (nonsteroidal anti-inflammatory drugs, indomethacin), those modifying neural transmission at the neuromuscular plate (magnesium sulfate), and calcium channel blockers (nifedipine). Nifedipine is considered as a first choice tocolytic and the most effective one in the prevention of preterm delivery (AU)


Assuntos
Humanos , Trabalho de Parto Prematuro , Nifedipino , Bloqueadores dos Canais de Cálcio , Trabalho de Parto Prematuro/prevenção & controle
17.
J Med Chem ; 55(15): 6716-23, 2012 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-22817559

RESUMO

Metaproterenol and isoproterenol are bronchodilators that provide a structural basis for many other bronchodilators currently in use. One of these structurally related bronchodilators is terbutaline; it is administered as a prodrug, bambuterol, and is metabolized (bioconverted) into terbutaline by butyrylcholinesterase (BChE). The metabolism rate can be affected by BChE gene polymorphism in the human population and BChE stereoselectivity. The aim of our study was to investigate inhibition of human BChE and acetylcholinesterase (AChE) with metaproterenol, isoproterenol, and newly synthesized racemic bisdimethylcarbamate derivatives of metaproterenol (metacarb) and isoproterenol (isocarb) and their (R)-enantiomers to see if their bioconversion is affected by BChE inhibition in the same way as that for bambuterol. Metacarb and isocarb proved to be selective BChE inhibitors, as they progressively inhibited AChE 960 to 80 times more slowly than BChE(UU). All studied cholinesterases displayed poor affinity for metaproterenol and isoproterenol, yet BChE(UU) had an affinity about five times higher than that of AChE.


Assuntos
Carbamatos/química , Inibidores da Colinesterase/química , Isoproterenol/análogos & derivados , Isoproterenol/química , Metaproterenol/análogos & derivados , Metaproterenol/química , Acetilcolinesterase/química , Butirilcolinesterase/química , Carbamatos/síntese química , Inibidores da Colinesterase/síntese química , Ensaios Enzimáticos , Humanos , Isoproterenol/síntese química , Metaproterenol/síntese química , Modelos Moleculares , Estereoisomerismo , Relação Estrutura-Atividade
18.
Cochrane Database Syst Rev ; (5): CD008585, 2012 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-22592732

RESUMO

BACKGROUND: Dysmenorrhoea is a common gynaecological complaint that can affect as many as 50% of premenopausal women, 10% of whom suffer severely enough to be rendered incapacitated for one to three days during each menstrual cycle. Primary dysmenorrhoea is where women suffer from menstrual pain but lack any pathology in their pelvic anatomy. Beta2-adrenoceptor agonists have been used in the treatment of women with primary dysmenorrhoea but their effects are unclear. OBJECTIVES: To determine the effectiveness and safety of beta2-adrenoceptor agonists in the treatment of primary dysmenorrhoea. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register; CENTRAL (The Cochrane Library 2011, Issue 8); MEDLINE; EMBASE; PsycINFO and the EBM Reviews databases. The last search was on 22 August 2011. SELECTION CRITERIA: Randomised controlled trials comparing beta2-adrenoceptor agonists with placebo or no treatment, each other or any other conventional treatment in women of reproductive age with primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. MAIN RESULTS: Five trials involving 187 women with an age range of 15 to 40 years were included. Oral isoxsuprine was compared with placebo in two trials; terbutaline oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared with placebo in a further three trials. Clinical diversity in the studies in terms of the interventions being evaluated, assessments at different time points and the use of different assessment tools mitigated against pooling of outcome data across studies in order to provide a summary estimate of effect for any of the comparisons. Only one study, with unclear risk of bias, reported pain relief with a combination of isoxsuprine, acetaminophen and caffeine. None of the other studies reported any significant clinical difference in effectiveness between the intervention and placebo. Adverse effects were reported with all of these medications in up to a quarter of the total number of participants. They included nausea, vomiting, dizziness, quivering, tremor and palpitations. AUTHORS' CONCLUSIONS: The evidence presented in this review was based on a few relatively small-sized studies that were categorised to have unclear to high risk of bias, which does not allow confident decision-making at present about the use of beta2-adrenoceptor agonists for dysmenorrhoea. The benefits as reported in one study should be balanced against the wide array of unacceptable side effects documented with this class of medication. We have emphasised the lack of precision and limitations in the reported data where appropriate.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Dismenorreia/tratamento farmacológico , Acetaminofen/uso terapêutico , Adolescente , Adulto , Cafeína/uso terapêutico , Feminino , Humanos , Isoxsuprina/uso terapêutico , Metaproterenol/análogos & derivados , Metaproterenol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritodrina/uso terapêutico , Terbutalina/uso terapêutico , Adulto Jovem
19.
Cochrane Database Syst Rev ; (4): CD003797, 2012 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-22513916

RESUMO

BACKGROUND: Inhaled anticholinergics as single agent bronchodilators (or in combination with beta(2)-agonists) are one of the several medications available for the treatment of acute asthma in children. OBJECTIVES: To determine the effectiveness of only inhaled anticholinergic drugs (i.e. administered alone), compared to a control in children over the age of two years with acute asthma. SEARCH METHODS: The Cochrane Register of Controlled Trials (CENTRAL), and the Cochrane Airways Group Register of trials were searched by the Cochrane Airways Group. The latest search was performed in April 2011. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) in which inhaled anticholinergics were given as single therapy and compared with placebo or any other drug or drug combinations for children over the age of two years with acute asthma. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data and assessed trial quality. MAIN RESULTS: Six studies met the inclusion criteria but were limited by small sample sizes, various treatment regimes used and outcomes assessed. The studies were overall of unclear quality. Data could only be pooled for the outcomes of treatment failure and hospitalisation. Other data could not be combined due to divergent outcome measurements. Meta-analysis revealed that children who received anticholinergics alone were significantly more likely to have treatment failure compared to those who received beta(2)-agonists from four trials on 171 children (odds ratio (OR) 2.27; 95% CI 1.08 to 4.75). Also, treatment failure on anticholinergics alone was more likely than when anticholinergics were combined with beta(2)-agonists from four trials on 173 children (OR 2.65; 95% CI 1.2 to 5.88). Data on clinical scores/symptoms that were measured on different scales were conflicting. Individual trials reported that lung function was superior in the combination group when compared with anticholinergic agents used alone. The use of anticholinergics was not found to be associated with significant side effects. AUTHORS' CONCLUSIONS: In children over the age of two years with acute asthma exacerbations, inhaled anticholinergics as single agent bronchodilators were less efficacious than beta(2)-agonists. Inhaled anticholinergics were also less efficacious than inhaled anticholinergics combined with beta(2)-agonists. Inhaled anticholinergic drugs alone are not appropriate for use as a single agent in children with acute asthma exacerbations.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Antagonistas Colinérgicos/administração & dosagem , Doença Aguda , Administração por Inalação , Adolescente , Albuterol/administração & dosagem , Atropina/administração & dosagem , Criança , Pré-Escolar , Quimioterapia Combinada/métodos , Fenoterol/administração & dosagem , Humanos , Ipratrópio/administração & dosagem , Metaproterenol/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Derivados da Escopolamina/administração & dosagem , Falha de Tratamento
20.
Sleep Breath ; 16(4): 1229-35, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22198635

RESUMO

OBJECTIVE: International guidelines recommend short- (SABA) or long-acting b-agonists for the prevention of bronchoconstriction after exercise (EIB) in patients with exercise-induced asthma (EIA). However, other drugs are still in discussion for the prevention of EIB. We investigated the efficacy of a combination of inhaled sodium cromoglycate and the ß-mimetic drug reproterol versus inhaled reproterol alone and both versus inhaled placebo in subjects with exercise-induced asthma (EIA). METHODS: The study aimed to prove the preventive effect of a combination of 1-mg reproterol and 2-mg disodium cromoglycate (DSCG) and its single components vs. placebo, measuring the decrease of FEV1 after a standardized treadmill test in 11 patients with recorded EIA. The study medication was twice as high as those of drugs which are commercially available (e.g., Allergospasmin®, Aarane®). RESULTS: The results revealed that the combination of reproterol and DSCG was significantly effective against a decrease of FEV1 after a standardized exercise challenge test (ECT) compared to placebo. The short-acting b-agonist reproterol alone had almost the same effectiveness as the combination of reproterol and DNCG. The difference between the combination with DNCG and reproterol alone was less than 10% and insignificant (p 0.48). DNCG alone did not show a difference in the effectiveness compared to placebo. CONCLUSION: Prevention of EIA with the combination of reproterol and DSCG or with reproterol only is effective. An exclusive recommendation in favor of the combination cannot be given due to the low difference in the effectiveness versus reproterol alone. Due to the limited number of subjects and some probands showing protection under DSCG, it cannot be completely excluded that there is some preventive power of DSCG in individual cases.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Antiasmáticos/uso terapêutico , Asma Induzida por Exercício/tratamento farmacológico , Cromolina Sódica/uso terapêutico , Metaproterenol/análogos & derivados , Teofilina/análogos & derivados , Administração por Inalação , Agonistas Adrenérgicos beta/efeitos adversos , Adulto , Antiasmáticos/efeitos adversos , Cromolina Sódica/efeitos adversos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Teste de Esforço , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Metaproterenol/efeitos adversos , Metaproterenol/uso terapêutico , Pessoa de Meia-Idade , Teofilina/efeitos adversos , Teofilina/uso terapêutico , Capacidade Vital/efeitos dos fármacos , Adulto Jovem
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