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1.
Food Chem ; 371: 131140, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34583185

RESUMO

The aim of this study is to develop a portable wireless intelligent nanosensor (PWIN) for rapid cost-effective on-site determination of terbutaline (TRA) residue in meat products outdoors in comparison with traditional nanosensor and high-performance liquid chromatography (HPLC). The layer-by-layer sandwiched nanohybrid fabricated by platinum-palladium nanoparticles, carboxylated graphene and graphene-like molybdenum disulfide displayed a wide linear range of 0.55-14.9 µmol/L using the portable potentiostat with smartphone, and the result was almost close to the linear range (0.4-14 µmol/L) using the traditional potentiostat with desktop computer for TRA. The limit of detections were identified as 0.44 µmol/L and 0.18 µmol/L, respectively. PWIN displayed satisfactory recovery (91%-98.43%) of TRA in samples by the standard addition method and in comparison with both traditional sensor (93.79%-98%) and HPLC (93.4%-98.6%), revealing that PWIN for rapid cost-effective on-site analysis in the food safety field is feasible.


Assuntos
Grafite , Produtos da Carne , Nanopartículas Metálicas , Técnicas Eletroquímicas , Eletrodos , Paládio , Terbutalina
2.
Life Sci ; 285: 119992, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592235

RESUMO

Terbutaline sulphate (TS) is a selective short-acting ß2 adrenoceptor agonist used for asthma treatment. The pharmacological activity of TS depends on its binding to the transmembrane protein, ß2 adrenoceptor. Thus, the interactions of this drug with biological membranes are expected, affecting its pharmacological activity. Using in vitro models to study the interaction of TS with biological membranes can provide important information about the activity of the drug. Here, liposomes with different lipid compositions were used as biomimetic models of cell membranes to evaluate the effect of composition, complexity, and physical state of membranes on TS-membrane interactions. For that, liposomes containing dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and liposomes containing DMPC and cholesterol (CHOL) were prepared. For the study of TS-membrane interactions, the TS lipophilicity was evaluated in terms of i) partition coefficient; ii) the preferential location of the drug within the membrane; iii) and the effect of TS on the membrane fluidity. The obtained data suggest that TS has an affinity for the lipid membrane, partitioning from the aqueous to the lipid phase. The affinity was dependent on the liposomes' compositions, showing a greater affinity for DMPC membranes than for DMPC:CHOL model. Dynamic light scattering (DLS) results revealed that this is due to the rigidizing effect caused by CHOL molecules. These findings provide valuable insights in the understanding of the complex interaction of TS with biomembrane models as well as the relevance of lipid compositions and membrane structure in such interactions, which may be related to its pharmacological activity and side effects.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Antiasmáticos/farmacologia , Materiais Biomiméticos/farmacologia , Membrana Celular/efeitos dos fármacos , Terbutalina/farmacologia , Antagonistas de Receptores Adrenérgicos beta 2/química , Antiasmáticos/química , Materiais Biomiméticos/química , Membrana Celular/química , Colesterol/química , Dimiristoilfosfatidilcolina/química , Difusão Dinâmica da Luz , Lipossomos/química , Terbutalina/química
3.
Front Immunol ; 12: 628065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220796

RESUMO

Objective: Hypersympathetic activity is prominent in rheumatoid arthritis, and major life stressors precede onset in ~80% of patients. These findings and others support a link between stress, the sympathetic nervous system and disease onset and progression. Here, we extend previous research by evaluating how selective peripherally acting α/ß2-adrenergic drugs affect joint destruction in adjuvant-induced arthritis. Methods: Complete Freund's adjuvant induced inflammatory arthritis in male Lewis rats. Controls received no treatment. Arthritic rats then received vehicle or twice-daily treatment with the α-adrenergic antagonist, phentolamine (0.5 mg/day) and the ß2-adrenergic agonist, terbutaline (1200 µg/day, collectively named SH1293) from day (D) of disease onset (D12) through acute (D21) and severe disease (D28). Disease progression was assessed in the hind limbs using dorsoplantar widths, X-ray analysis, micro-computed tomography, and routine histology on D14, D21, and D28 post-immunization. Results: On D21, SH1293 significantly attenuated arthritis in the hind limbs, based on reduced lymphocytic infiltration, preservation of cartilage, and bone volume. Pannus formation and sympathetic nerve loss were not affected by SH1293. Bone area and osteoclast number revealed high- and low-treatment-responding groups. In high-responding rats, treatment with SH1293 significantly preserved bone area and decreased osteoclast number, data that correlated with drug-mediated joint preservation. SH1293 suppressed abnormal bone formation based on reduced production of osteophytes. On D28, the arthritic sparing effects of SH1293 on lymphocytic infiltration, cartilage and bone sparing were maintained at the expense of bone marrow adipocity. However, sympathetic nerves were retracted from the talocrural joint. Conclusion and Significance: Our findings support a significant delay in early arthritis progression by treatment with SH1293. Targeting sympathetic neurotransmission may provide a strategy to slow disease progression.


Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Artrite Experimental/prevenção & controle , Articulações/efeitos dos fármacos , Fentolamina/farmacologia , Receptores Adrenérgicos alfa/efeitos dos fármacos , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Terbutalina/farmacologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Combinação de Medicamentos , Adjuvante de Freund , Articulações/diagnóstico por imagem , Articulações/metabolismo , Articulações/patologia , Masculino , Ratos Endogâmicos Lew , Receptores Adrenérgicos alfa/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Transdução de Sinais
6.
Cochrane Database Syst Rev ; 5: CD013518, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33945639

RESUMO

BACKGROUND: Asthma affects 350 million people worldwide including 45% to 70% with mild disease. Treatment is mainly with inhalers containing beta2-agonists, typically taken as required to relieve bronchospasm, and inhaled corticosteroids (ICS) as regular preventive therapy. Poor adherence to regular therapy is common and increases the risk of exacerbations, morbidity and mortality. Fixed-dose combination inhalers containing both a steroid and a fast-acting beta2-agonist (FABA) in the same device simplify inhalers regimens and ensure symptomatic relief is accompanied by preventative therapy. Their use is established in moderate asthma, but they may also have potential utility in mild asthma. OBJECTIVES: To evaluate the efficacy and safety of single combined (fast-onset beta2-agonist plus an inhaled corticosteroid (ICS)) inhaler only used as needed in people with mild asthma. SEARCH METHODS: We searched the Cochrane Airways Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, ClinicalTrials.gov and the World Health Organization (WHO) trials portal. We contacted trial authors for further information and requested details regarding the possibility of unpublished trials. The most recent search was conducted on 19 March 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over trials with at least one week washout period. We included studies of a single fixed-dose FABA/ICS inhaler used as required compared with no treatment, placebo, short-acting beta agonist (SABA) as required, regular ICS with SABA as required, regular fixed-dose combination ICS/long-acting beta agonist (LABA), or regular fixed-dose combination ICS/FABA with as required ICS/FABA. We planned to include cluster-randomised trials if the data had been or could be adjusted for clustering. We excluded trials shorter than 12 weeks. We included full texts, abstracts and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We analysed dichotomous data as odds ratios (OR) or rate ratios (RR) and continuous data as mean difference (MD). We reported 95% confidence intervals (CIs). We used Cochrane's standard methodological procedures of meta-analysis. We applied the GRADE approach to summarise results and to assess the overall certainty of evidence. Primary outcomes were exacerbations requiring systemic steroids, hospital admissions/emergency department or urgent care visits for asthma, and measures of asthma control. MAIN RESULTS: We included six studies of which five contributed results to the meta-analyses. All five used budesonide 200 µg and formoterol 6 µg in a dry powder formulation as the combination inhaler. Comparator fast-acting bronchodilators included terbutaline and formoterol. Two studies included children aged 12+ and adults; two studies were open-label. A total of 9657 participants were included, with a mean age of 36 to 43 years. 2.3% to 11% were current smokers. FABA / ICS as required versus FABA as required Compared with as-required FABA alone, as-required FABA/ICS reduced exacerbations requiring systemic steroids (OR 0.45, 95% CI 0.34 to 0.60, 2 RCTs, 2997 participants, high-certainty evidence), equivalent to 109 people out of 1000 in the FABA alone group experiencing an exacerbation requiring systemic steroids, compared to 52 (95% CI 40 to 68) out of 1000 in the FABA/ICS as-required group. FABA/ICS as required may also reduce the odds of an asthma-related hospital admission or emergency department or urgent care visit (OR 0.35, 95% CI 0.20 to 0.60, 2 RCTs, 2997 participants, low-certainty evidence). Compared with as-required FABA alone, any changes in asthma control or spirometry, though favouring as-required FABA/ICS, were small and less than the minimal clinically-important differences. We did not find evidence of differences in asthma-associated quality of life or mortality. For other secondary outcomes FABA/ICS as required was associated with reductions in fractional exhaled nitric oxide, probably reduces the odds of an adverse event (OR 0.82, 95% CI 0.71 to 0.95, 2 RCTs, 3002 participants, moderate-certainty evidence) and may reduce total systemic steroid dose (MD -9.90, 95% CI -19.38 to -0.42, 1 RCT, 443 participants, low-certainty evidence), and with an increase in the daily inhaled steroid dose (MD 77 µg beclomethasone equiv./day, 95% CI 69 to 84, 2 RCTs, 2554 participants, moderate-certainty evidence). FABA/ICS as required versus regular ICS plus FABA as required There may be little or no difference in the number of people with asthma exacerbations requiring systemic steroid with FABA/ICS as required compared with regular ICS (OR 0.79, 95% CI 0.59 to 1.07, 4 RCTs, 8065 participants, low-certainty evidence), equivalent to 81 people out of 1000 in the regular ICS plus FABA group experiencing an exacerbation requiring systemic steroids, compared to 65 (95% CI 49 to 86) out of 1000 FABA/ICS as required group. The odds of an asthma-related hospital admission or emergency department or urgent care visit may be reduced in those taking FABA/ICS as required (OR 0.63, 95% CI 0.44 to 0.91, 4 RCTs, 8065 participants, low-certainty evidence). Compared with regular ICS, any changes in asthma control, spirometry, peak flow rates (PFR), or asthma-associated quality of life, though favouring regular ICS, were small and less than the minimal clinically important differences (MCID). Adverse events, serious adverse events, total systemic corticosteroid dose and mortality were similar between groups, although deaths were rare, so confidence intervals for this analysis were wide. We found moderate-certainty evidence from four trials involving 7180 participants that FABA/ICS as required was likely associated with less average daily exposure to inhaled corticosteroids than those on regular ICS (MD -154.51 µg/day, 95% CI -207.94 to -101.09). AUTHORS' CONCLUSIONS: We found FABA/ICS as required is clinically effective in adults and adolescents with mild asthma. Their use instead of FABA as required alone reduced exacerbations, hospital admissions or unscheduled healthcare visits and exposure to systemic corticosteroids and probably reduces adverse events. FABA/ICS as required is as effective as regular ICS and reduced asthma-related hospital admissions or unscheduled healthcare visits, and average exposure to ICS, and is unlikely to be associated with an increase in adverse events. Further research is needed to explore use of FABA/ICS as required in children under 12 years of age, use of other FABA/ICS preparations, and long-term outcomes beyond 52 weeks.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Budesonida/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Adolescente , Adulto , Beclometasona/administração & dosagem , Criança , Progressão da Doença , Combinação de Medicamentos , Hospitalização/estatística & dados numéricos , Humanos , Nebulizadores e Vaporizadores , Prednisolona/administração & dosagem , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Terbutalina/administração & dosagem
7.
J Allergy Clin Immunol Pract ; 9(8): 3069-3077.e6, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33895362

RESUMO

BACKGROUND: Medication adherence is challenging for adolescents. In mild asthma, as-needed budesonide-formoterol (BUD-FORM) reduces severe exacerbations compared with as-needed short-acting beta2-agonists, similar to the reduction with maintenance budesonide. OBJECTIVE: This post hoc pooled analysis of Symbicort Given as-needed in Mild Asthma (SYGMA) 1 and 2 assessed the efficacy and safety of as-needed BUD-FORM in adolescents. METHODS: SYGMA 1 and 2 were 52-week, double-blind studies (NCT022149199; NCT02224157) in patients 12 years or older with mild asthma. Patients were randomized to twice-daily placebo + as-needed BUD-FORM 200/6 µg, twice-daily BUD 200 µg + as-needed terbutaline (BUD maintenance), or twice-daily placebo + as-needed terbutaline 0.5 mg (SYGMA 1 only). Annualized severe exacerbation rates, maintenance treatment adherence, and safety (including change in height) were compared between treatment groups in adolescents (aged ≥12 to <18 years). RESULTS: Severe exacerbation rate was similar with as-needed BUD-FORM and BUD maintenance (pooled analysis: 0.08 vs 0.07/y; P = .634), and was significantly lower with as-needed BUD-FORM versus as-needed terbutaline (SYGMA 1: 0.04 vs 0.17/y; P = .005). Median adherence was 73% in SYGMA 1 and 51% in SYGMA 2. Change in height from baseline in adolescents aged ≥12 years to <14 years was significantly greater with as-needed BUD-FORM (4.8 cm) versus BUD maintenance (3.9 cm) (pooled: P < .046), and was similar between as-needed BUD-FORM (4.5 cm) and as-needed terbutaline (4.1 cm) (SYGMA 1: P = .500). No new or unexpected safety concerns were identified. CONCLUSIONS: In adolescents with mild asthma, as-needed BUD-FORM was superior to as-needed terbutaline for severe exacerbation reduction, with similar efficacy to BUD maintenance. As-needed BUD-FORM provides an alternative treatment option for adolescents with mild asthma, without needing daily treatment.


Assuntos
Asma , Budesonida , Administração por Inalação , Adolescente , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Budesonida/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Etanolaminas/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Humanos , Terbutalina/uso terapêutico , Resultado do Tratamento
8.
Eur J Pharm Sci ; 161: 105782, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33675911

RESUMO

Milling may cause undesired changes in crystal topology, due to exposure of new facets, their corresponding functional groups and surface amorphization. This study investigated effect of milling induced surface amorphous content and chemical environment on moisture sorption behavior of a model hydrophilic drug, Terbutaline Sulphate (TBS). A Dynamic Vapor Sorption (DVS) based analytical method was developed to detect amorphous content, with LOD and LOQ of 0.41% and 1.24%w/w, respectively. The calibration curve gave a linear regression of 0.999 in a concentration range of 0-16.36%w/w amorphous content plotted against surface area normalized % weight change, due to moisture sorption. TBS was milled using air jet mill at 8 Bars for 3 cycles (D90- 3.46µm) and analyzed using the validated DVS method prior to and post conditioning. The moisture sorption was higher in case of milled unconditioned TBS. Molecular Dynamics Simulation (MDS) was performed to identify the cause for increased moisture sorption due to altered surface environment or amorphous content. The results implied that the new planes and functional groups exposed on milling had negligible contribution to moisture sorption and the higher moisture sorption in milled unconditioned TBS was due to surface amorphization. Conditioning under elevated humidity recrystallized the milling-induced surface amorphous content and led to decreased moisture sorption in milled conditioned TBS.


Assuntos
Simulação de Dinâmica Molecular , Terbutalina , Cristalização , Umidade , Interações Hidrofóbicas e Hidrofílicas
9.
J Physiol Sci ; 71(1): 7, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618673

RESUMO

BACKGROUND: Currently available tocolytic agents are not effective treatment for preterm labor beyond 48 h. A major reason is the development of maternal side effects which preclude the maintenance of an effective steady-state drug concentration. One strategy that can mitigate these side effects is utilizing synergistic drug combinations to reduce the drug concentrations necessary to elicit a clinical effect. We have previously shown that three anoctamin 1 (ANO1) antagonists mediate potent relaxation of precontracted human uterine smooth muscle (USM). In this study, we aimed to determine whether a combination of sub-relaxatory doses of tocolytic drugs in current clinical use [the L-type voltage-gated calcium channel (VGCC) blocker, nifedipine (NIF); and the ß2-adrenergic (ß2AR) agonist, terbutaline (TRB)] will potentiate USM relaxation with two ANO1 antagonists [benzbromarone (BB) and MONNA (MN)]. OBJECTIVE: This study sought to examine the synergistic potency and mechanistic basis of two ANO1 antagonists with currently available tocolytic drugs. Functional endpoints assessed included relaxation of pre-contracting pregnant human USM tissue, inhibition of intracellular calcium release, and reduction of spontaneous transient inward current (STIC) recordings in human uterine smooth muscle cells. METHODS: Human myometrial strips and primary human USM cells were used in organ bath and calcium flux experiments with different combinations of sub-threshold doses of ANO1 antagonists and terbutaline or nifedipine to determine if ANO1 antagonists potentiate tocolytic drugs. RESULTS: The combination of sub-threshold doses of two ANO1 antagonists and current tocolytic drugs demonstrate a significant degree of synergy to relax human pregnant USM compared to the effects achieved when these drugs are administered individually. CONCLUSION: A combination of sub-threshold doses of VGCC blocker and ß2AR agonist with ANO1 antagonists potentiates relaxation of oxytocin-induced contractility and calcium flux in human USM ex vivo. Our findings may serve as a foundation for novel tocolytic drug combinations.


Assuntos
Anoctamina-1/antagonistas & inibidores , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Nifedipino/farmacologia , Terbutalina/farmacologia , Útero/fisiologia , Benzobromarona/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Gravidez , Técnicas de Cultura de Tecidos , Tocolíticos/farmacologia , Uricosúricos/farmacologia , ortoaminobenzoatos/farmacologia
10.
J Biomater Sci Polym Ed ; 32(4): 524-535, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33175639

RESUMO

Bronchial asthma is a chronic disease which is currently treated using various inhalants. However, the medication adherence with the inhalants is poor due to complex procedure to use them along with frequent dosing. In this paper, we have developed tulobuterol loaded Pluronic® F127-reduced graphene oxide transdermal hydrogel to sustain the release of tulobuterol to manage asthma for days. The synthesis of Pluronic® F127-reduced graphene oxide was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy. The transmission electron microscope showed wrinkled flat nano sheets. The hydrogel showed sufficient mechanical properties for topical application and was safe in the skin irritation study (rabbit model). The ex vivo release data demonstrated the ability of reduced graphene oxide to sustain the release of tulobuterol for 72 h, due to strong π-π interaction between drug and graphene oxide. The pharmacokinetic profile in Sprague-Dawley rat model confirmed the potential of tulobuterol-Pluronic® F127-reduced graphene oxide hydrogel to sustain the release of tulobuterol for effective management of asthma.


Assuntos
Asma , Grafite , Animais , Asma/tratamento farmacológico , Preparações de Ação Retardada , Hidrogéis , Coelhos , Ratos , Ratos Sprague-Dawley , Terbutalina/análogos & derivados
11.
J Chromatogr A ; 1637: 461835, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33383241

RESUMO

High-performance affinity chromatography is limited by its high cost and high pressure. Paper is made up of porous fiber networks and has the properties of low cost, ease of fabrication, and biodegradable. Due to these advantages, herein, we immobilized beta2-adrenoceptor (ß2-AR) onto the surface of the polytetrafluoroethylene membrane, a paper-based material, and constructed a G protein-coupled receptor (GPCR)-in-paper chromatographic platform. This platform was characterized by Fourier transform infrared spectroscopy, fluorescence analysis, X-ray photoelectron spectroscopy, and chromatographic studies. These morphological and elemental analysis showed that ß2-AR was successfully immobilized on the paper surface. The specific drugs have good retentions on the GPCR-in-paper chromatographic platform. The association constants of salbutamol, terbutaline and bambuterol to ß2-AR were calculated to be 2.02 × 104 M-1, 1.15 × 104 M-1, 1.75 × 104 M-1 by adsorption energy distribution, which were in good line with the values from frontal analysis, zonal elution and previous literatures. We demonstrated that the GPCR-in-paper platform was cost-effective, easy to be modified for protein immobilization, and applicable in the receptor-drug interaction analysis. We believe such a platform sheds new light on paper chromatography for receptor-drug interaction analysis and other applications.


Assuntos
Albuterol/metabolismo , Cromatografia em Papel/métodos , Receptores Adrenérgicos beta 2/metabolismo , Terbutalina/análogos & derivados , Terbutalina/metabolismo , Adsorção , Interações Medicamentosas , Proteínas de Ligação ao GTP/metabolismo , Ligantes
12.
PLoS One ; 15(12): e0244253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33347508

RESUMO

In order to elucidate involvement of cyclic AMP and intracellular Ca2+,[Ca2+]i, in the modulation of aqueous humour formation (AHF), we studied the effects of terbutaline, forskolin and 8-Br-cAMP in the isolated bovine eye. We also studied the interaction of cAMP on calcium signaling in cultured ciliary epithelial (CE) cells. Drug effects on AHF were measured by fluorescein dilution. Drug effects on [Ca2+]i were studied by the fura-2 fluorescence ratio technique. Terbutaline (100 nmol-100 M), forskolin (30 nM-100 M) or 8-Br-cAMP (100 nM- 10 µM), administered in the arterial perfusate produced significant reductions in AHF. The AH reducing effect of terbutaline was blocked by a selective inhibitor of protein kinase A (KT-5720). ATP (100 M) caused a rapid, transient (peak) increase in [Ca2+]i followed by a sustained plateau phase lasting more than 5 minutes. Preincubation of the cells (6 min) with terbutaline, forskolin or 8-Br-cAMP significantly reduced the peak calcium response to ATP. The sustained plateau phase of the response, on the other hand, was augmented by each of the agents. KT-5720 partially reversed the inhibitory effect of terbutaline on the peak and totally inhibited its effect on the plateau phase. These data indicate: (a) that AHF in the bovine eye can be manipulated through cyclic AMP, operating via protein kinase A, (b) that protein kinase A can affect [Ca2+]i homeostasis, (c) that calcium release from the intracellular store, not the entry, affects AHF, and (d) that interaction of [Ca2+]i with cAMP plays a role in modulating AH secretion.


Assuntos
Humor Aquoso/metabolismo , Secreções Corporais/efeitos dos fármacos , Cálcio/metabolismo , Colforsina/farmacologia , AMP Cíclico/farmacologia , Terbutalina/farmacologia , Animais , Humor Aquoso/efeitos dos fármacos , Broncodilatadores/farmacologia , Bovinos , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
13.
Ann Palliat Med ; 9(5): 3393-3401, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065789

RESUMO

BACKGROUND: The pathogenesis of chronic obstructive pulmonary disease (COPD) is complex. Our study aimed to investigate the clinical value of N-acetylcysteine (NAC) combined with terbutaline sulfate in the treatment of COPD in elderly people, and its effect on the apoptosis/anti-apoptosis mechanism. METHODS: A total of 126 elderly COPD patients in our hospital from December 2017 to June 2019 were recruited and divided into 3 groups. On the basis of conventional treatment, control group A was treated with NAC, control group B with terbutaline sulfate, and combined group with both drugs. Lung function, apoptosis/anti-apoptosis related indexes, oxidative stress indexes, COPD assessment test (CAT) score, 6-min walk distance (6MWD), blood gas indexes, and adverse reactions were measured. RESULTS: The levels of forced vital capacity (FVC), maximum mid-expiratory flow rate (MMF), peak expiratory flow (PEF), oxygenation index (OI), and blood oxygen saturation (SaO2) in 3 groups were increased after treatment, and were the highest in the combined group. The level of carbon dioxide partial pressure (PaCO2) was decreased, and was the lowest in the combined group. After 2 weeks of treatment, the 6MWD had increased in all 3 groups and was longest in the combined group. The CAT score was decreased and the extent of decrease was the highest in the combined group. After treatment, the levels of Fas receptor/apoptosis antigen 1 (Fas/APO-1), soluble Fas (sFas), malondialdehyde (MDA), and reactive oxygen species (ROS) in the three groups were decreased, and their levels were decreased most markedly in the combined group. Meanwhile, the levels of superoxide dismutase (SOD) and glutathione peroxide enzyme (GSH-PX) were increased after treatment, and their levels were the highest in the combined group. The incidence of dizziness, chest tightness, constipation, and nasal congestion in the combination group were not significantly different from the other two groups. CONCLUSIONS: The combined use of terbutaline sulfate and NAC in the treatment of elderly patients with COPD can effectively improve their lung function and blood gas status, which can strengthen athletic ability, reduce the oxidative stress response, and regulate apoptotic cytokines.


Assuntos
Acetilcisteína , Doença Pulmonar Obstrutiva Crônica , Acetilcisteína/uso terapêutico , Idoso , Apoptose , Humanos , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Terbutalina/uso terapêutico
14.
N Z Med J ; 133(1520): 61-72, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994594

RESUMO

AIM: In the PRACTICAL study, as-needed budesonide/formoterol reduced the rate of severe exacerbations compared with maintenance budesonide plus as-needed terbutaline. In a pre-specified analysis we analysed the efficacy in Maori and Pacific peoples, populations with worse asthma outcomes. METHOD: The PRACTICAL study was a 52-week, open-label, parallel group, randomised controlled trial of 890 adults with mild to moderate asthma, who were randomised to budesonide/formoterol Turbuhaler 200/6mcg one actuation as required or budesonide Turbuhaler 200mcg one actuation twice daily and terbutaline Turbuhaler 250mcg two actuations as required. The primary outcome was rate of severe exacerbations. The analysis strategy was to test an ethnicity-treatment interaction term for each outcome variable. RESULTS: Seventy-two participants (8%) identified as Maori, 36 participants (4%) as Pacific ethnicity. There was no evidence that ethnicity was an effect modifier for severe exacerbations (P interaction 0.70). CONCLUSION: The reduction in severe exacerbation risk with budesonide-formoterol reliever compared with maintenance budesonide was similar in Maori and Pacific adults compared with New Zealand European/Other.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Quimioterapia Combinada/métodos , Administração por Inalação , Adulto , Antiasmáticos/administração & dosagem , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Estudos de Casos e Controles , Progressão da Doença , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores/normas , Nova Zelândia/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Terbutalina/administração & dosagem , Terbutalina/uso terapêutico , Resultado do Tratamento
15.
J Microencapsul ; 37(8): 577-594, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969722

RESUMO

AIM: The present work aimed to improve the bioavailability of terbutaline sulphate (TS) and to prolong its nasal residence time for the treatment of asthma. METHODS: Chitosan/pectin polyelectrolyte complex nanoparticles (CS/PC) were prepared by ionic gelation method and coated with phospholipid (PL) and then incorporated into optimised thermosensitive in situ gel. RESULTS: The optimal PL-coated nanoparticle formulation (LP1) showed the smallest particle size (345.5 nm), the highest zeta potential (32.9 mV) and the greatest percent drug released after 6 h (71%). The optimum in situ gel loaded with LP1 (NG3) showed three times greater permeation through nasal mucosa than aqueous solution of TS and revealed about 94% and 92% of the effect of IV injection of drug solution on tidal volume and peak expiratory flow in histamine treated rats, respectively. CONCLUSION: The developed PL-coated CS/PC/in situ gel could be considered as a promising intranasal formulation of TS for asthma management.


Assuntos
Administração Intranasal , Lipídeos/química , Nanopartículas/química , Polímeros/química , Terbutalina/química , Animais , Asma/terapia , Quitosana/química , Sistemas de Liberação de Medicamentos , Cinética , Masculino , Teste de Materiais , Microscopia Eletrônica de Transmissão , Nanotecnologia , Tamanho da Partícula , Pectinas/química , Fosfolipídeos/química , Polieletrólitos , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
17.
Thorax ; 75(10): 842-848, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32719055

RESUMO

BACKGROUND: An as-needed combination preventer and reliever regimen was recently introduced as an alternative to conventional daily preventer treatment for mild asthma. In a subgroup analysis of the PRACTICAL study, a pragmatic randomised controlled trial of budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild asthma, we recently reported that about two-thirds preferred as-needed combination preventer and reliever therapy. The aim of this study was to determine the relative importance of attributes associated with these two asthma therapies in this subgroup of participants who indicated their preferred treatment in the PRACTICAL study. METHODS: At their final study visit, a subgroup of participants indicated their preferred treatment and completed a discrete choice experiment using the Potentially All Pairwise RanKings of all possible Alternatives method and 1000minds software. Treatment attributes and their levels were selected from measurable study outcomes, and included: treatment regimen, shortness of breath, steroid dose and likelihood of asthma flare-up. RESULTS: The final analysis dataset included 288 participants, 64% of whom preferred as-needed combination preventer and reliever. Of the attributes, no shortness of breath and lowest risk of asthma flare-up were ranked highest and second highest, respectively. However, the relative importance of the other two attributes varied by preferred therapy: treatment regimen was ranked higher by participants who preferred as-needed treatment than by participants who preferred maintenance treatment. CONCLUSIONS: Knowledge of patient preferences for treatment attributes together with regimen characteristics can be used in shared decision-making regarding choice of treatment for patients with mild-moderate asthma. TRIAL REGISTRATION NUMBER: ACTRN12616000377437.


Assuntos
Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Participação do Paciente , Preferência do Paciente , Terbutalina/uso terapêutico , Adulto , Tomada de Decisão Compartilhada , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Transplant Proc ; 52(9): 2817-2819, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32560969

RESUMO

The significance of serotonin syndrome due to drug-drug interactions has emerged as a prominent consideration when the effects of polypharmacy are reviewed. The emergence of the selective serotonin reuptake inhibitors has most likely fueled the increased reporting of serotonin syndrome in the literature, leading to increased awareness of this phenomenon. However, their presence is not necessarily inclusive to a case and the utilization of agents precipitating an occurrence may be unavoidable. We report a case of serotonin syndrome occurring in a heart transplant patient without the presence of any of the usual suspect agents involved. In the postoperative course, the patient developed cardiogenic shock with vasoplegia requiring continuation of inotropic therapy along with vasopressor support of epinephrine. Oral terbutaline was begun for hemodynamic improvement. The patient's tenuous mental status rapidly deteriorated after addition of the terbutaline, with symptoms consistent with serotonin syndrome. Administration of cyproheptadine, a known reversal agent for serotonin toxicity, rapidly alleviated the adverse symptoms.


Assuntos
Cardiotônicos/efeitos adversos , Transplante de Coração , Síndrome da Serotonina/etiologia , Terbutalina/efeitos adversos , Cardiotônicos/administração & dosagem , Ciproeptadina/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Pessoa de Meia-Idade , Polimedicação , Síndrome da Serotonina/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Terbutalina/administração & dosagem
19.
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
20.
Aust N Z J Obstet Gynaecol ; 60(6): 884-889, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32378185

RESUMO

AIM: To determine if a policy recommending administration of terbutaline prior to emergency caesarean section improved arterial umbilical cord pH. MATERIALS AND METHODS: This was a prospective audit between February 2018 and June 2019 among women who underwent a category one or two caesarean section. Neonatal cord gas results and perinatal outcomes were compared before and after the introduction of a policy recommending subcutaneous terbutaline prior to emergency caesarean section. RESULTS: Among 423 women in the pre-policy change cohort and 253 post-policy change, there was no difference in arterial cord pH (median pH = 7.24 before the policy and median pH = 7.24 after the policy was introduced, P = 0.88). There was no statistically significant difference in any perinatal outcome, apart from the median arterial cord lactate which was higher in the post-treatment group (4.2 mmol/L vs 3.9 mmol/L, P = 0.006). Maternal heart rate was higher (median 110 vs 95, P < 0.0001) in the post-treatment group. Breastfeeding was more common in the post-treatment group (99% vs 95%, P = 0.005). There was no difference in estimated blood loss or rate of post-partum haemorrhage. A post hoc analysis according to treatment received, limited to caesarean section when the indication was suspected fetal compromise, demonstrated that among women who received terbutaline the rate of low pH (<7.1) was 3.8% (5/130) when terbutaline was given, compared with 6.6% (18/272) when terbutaline was not given (χ2 1  = 1.3, P = 0.26). CONCLUSION: Changing our labour ward policy to recommending terbutaline prior to all category one and category two caesarean sections did not change arterial cord pH.


Assuntos
Cesárea/estatística & dados numéricos , Terbutalina/administração & dosagem , Tocólise/métodos , Tocolíticos/administração & dosagem , Adulto , Tratamento de Emergência , Feminino , Humanos , Trabalho de Parto , Trabalho de Parto Prematuro , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Resultado do Tratamento , Cordão Umbilical/irrigação sanguínea , Cordão Umbilical/efeitos dos fármacos
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