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The crystallization of active pharmaceutical ingredients (APIs) in matrix-type transdermal patches has implications for the rate of drug absorption through the skin and patch adhesion strength. Therefore, the presence or absence and the degree of API crystallinity must be controlled to guarantee the quality of patches. In this study, the utility of laboratory-level X-ray diffractometers for the detection and analysis of crystalline APIs in transdermal patches was investigated using medical patches of tulobuterol and isosorbide dinitrate. Several matrix-type patches employ a controlled drug delivery system containing intentionally crystallized API. Both benchtop and high-resolution laboratory X-ray diffractometers can detect several characteristic peaks of the APIs in these patches even if the patches are wrapped in an outer bag, although a benchtop model provides peak heights one-seventh to one-fifth that of a high-resolution instrument. An isosorbide dinitrate patch containing an unintentionally crystallized spot was wrapped in an outer bag, followed by measurements using both X-ray diffractometers. For both instruments, several isosorbide dinitrate-derived peaks were detected only at the crystallized spot, although the signal-to-noise ratio was poorer for the benchtop model. These results show that a high-resolution X-ray diffractometer is advantageous for high-detection sensitivity and offers a high degree of freedom of the measurement position on the sample. It was concluded that a laboratory-level high-resolution X-ray diffractometer can be used to examine the crystalline state of APIs in patches inside an unopened outer bag.

Urethral obstruction is always an emergency for male ferrets and can lead to hyperkalemia. Surgical treatment under general anesthesia can be required. Untreated hyperkalemia before anesthetic induction can be fatal. A 2-year-old, 1.01 kg, neutered male ferret (Mustela putorius furo) was presented for lethargy, hematuria, and stranguria. Radiographs revealed urolithiasis involving the bladder and urethra. When presented for anesthesia, the ferret had hyperkalemia. Before anesthesia, the potassium was normalized rapidly through a combination of saline, dextrose, insulin, and terbutaline. Terbutaline was added to the therapeutic regime as a result of persistent hyperkalemia. Severe hypotension developed during anesthesia which can be partially attributed to the peripheral vasodilatory effect of terbutaline. Hypoglycemia developed as a result of failure to monitor blood glucose level frequently during surgery and suboptimal regime used for insulin and dextrose. Potassium level in a hyperkalemic ferret can be normalized before anesthesia with a combination of therapeutic agents like saline, sodium bicarbonate, insulin, and dextrose. In a case of persistent hyperkalemia, terbutaline can be added to the therapeutic plan. It is important that blood pressure and blood glucose level are monitored closely to prevent hypotension possibly due to terbutaline and hypoglycemia as a result of insulin. The purpose of this report is to describe a case of a ferret with hyperkalemia that needed rapid correction before anesthesia.

Introduction Asthma is a common reason for presentation to the Emergency Department and is associated with significant morbidity and mortality. While patients may have a relatively benign course, there is a subset of patients who present in a critical state and require emergent management. Objective This narrative review provides evidence-based recommendations for the assessment and management of patients with severe asthma. Discussion It is important to consider a broad differential diagnosis for the cause and potential mimics of asthma exacerbation. Once the diagnosis is determined, the majority of the assessment is based upon the clinical examination. First line therapies for severe exacerbations include inhaled short-acting beta agonists, inhaled anticholinergics, intravenous steroids, and magnesium. Additional therapies for refractory cases include parenteral epinephrine or terbutaline, helium‑oxygen mixture, and consideration of ketamine. Intravenous fluids should be administered, as many of these patients are dehydrated and at risk for hypotension if they receive positive pressure ventilatory support. Noninvasive positive pressure ventilation may prevent the need for endotracheal intubation. If mechanical ventilation is required, it is important to avoid breath stacking by setting a low respiratory rate and allowing permissive hypercapnia. Patients with severe asthma exacerbations will require intensive care unit admission. Conclusions This review provides evidence-based recommendations for the assessment and management of severe asthma with a focus on the emergency clinician.

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

Introduction: Salbutamol and terbutaline are short-acting β2 adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by β2 adrenergic agonists. Methods: This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization. A double-blind crossover study was performed over 3 days, in order to compare the effects of each bronchodilator. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal expiratory flow 25-75 (MEF25-75) were measured. Results: On the first day, a bronchoconstriction caused by deep and repeated inhalations was eliminated. On the second day, an airway obstruction was confirmed by a decrease in FEV1 at 40% from baseline values after nebulization of a standard dose of terbutaline. On the third day, a spirometry was performed before and after nebulization of a standard dose of ipratropium bromide, and there were no significant changes in the spirometric parameters. Finally the patient was discharged with a written warning mentioning the danger of salbutamol and terbutaline use. Conclusion: Salbutamol and terbutaline are generally well-tolerated β2 adrenergic agonists. Nevertheless, in rare cases, these substances can cause a paradoxical bronchoconstriction. Doctors must therefore remain vigilant about its side effect and possibly investigate each case.

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.

BackgroundAn 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.MethodsAt 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.ResultsThe 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.ConclusionsKnowledge 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 numberACTRN12616000377437.

External cephalic version is a technique that decreases the need for cesarean delivery in patients with breech presentation. Several techniques exist to increase the success of external cephalic version; however, there are no studies comparing different tocolytics in patients who also received neuraxial anesthesia. We, therefore, performed a review of 198 patients who presented for external cephalic version and compared their success rates based on the tocolytic medication utilized. The external cephalic version success rate for patients who received terbutaline was significantly higher than for those who received nitroglycerin (N [%]: 57 [65.6] terbutaline group versus 40 [36.0] nitroglycerin group; P < .001).

Many factors affect the pulmonary drug delivery and stability of the nanoparticles an acupuncture consisting of bronchial asthma. Present research envisages on the development of dry powder nanoparticles as insufflation a acupuncture consisting of bronchial asthma (allergy due to Aspergillus fumigatus) using physical mixing and spray drying. Different founding are prepared and characterized with suitable excipients like lactose and trehalose. The particle size distribution of nano milled and spray-dried particles of Terbutaline Sulphate and Itraconazole showed unimodal size distribution. The formulations prepared with trehalose as the carrier showed less Dv90, Dv50 and Dv10 values due to the fineness in the particles of trehalose when compared to lactose. The Dv50 and Dv10 values were in the range of mountains of 0.43-0.89 µm and 0.21–0.49 µm for all formulations, which shows the primary particle size in the nanometer scale. Smooth and nearly spherical particles were produced for spray-dried formulations when compared to milled formulations. Zeta potential comes across until be between +17±0.13 to +32±0.12, which explains the particles as moderately stable. MMAD values ranges from 3.19 µm to 4.78 µm for milled nanoparticles and 3.45 µm to 4.21 µm for spray-dried particles. Formulated nanoparticles exhibited good spreading properties, which will allow all the particles to deposition palmy profusion territories consisting of the lung. In-vitro drug release studies explains that spray-dried formulations of Terbutaline sulpahte and Itraconazole using lactose as excipients released the drug upto 98.9% and 99.1% in 180mts.

The use of performance-enhancing drugs is prohibited in sports competitions according to the World Anti-Doping Agency (WADA) regulations. Here, ATR-FTIR spectroscopy coupled with a partial least squares regression (PLSR) chemometric tool was used for the detection of the misuse of such substances. Bambuterol and its metabolite terbutaline have been included in the list of prohibited doping agents. Therefore, we used bambuterol and terbutaline as models for the accurate and simultaneous qualitative and quantitative analysis of bambuterol and terbutaline in human urine samples. The method was straightforward and once the urine samples were collected, they could be directly applied to the surface of the ZnSe prism (ATR unit) to get the results within one minute. A calibration set with a partial factorial design was used to develop the PLSR model that could be used to predict the concentration of unknown samples containing the two drugs. The developed method was carefully validated and successfully applied to the urine sample analysis of human volunteers. The drugs were quantified at nanogram level concentrations. A side-by-side comparison of the proposed method with the routine GC-MS method was performed to demonstrate the challenges and opportunities of each method.

Background Before the advent of antenatal steroids, early non-invasive respiratory support (NIV), and intratracheal surfactant, antenatal terbutaline was also used to improve lung compliance and reduce the incidence of respiratory distress syndrome (RDS). Objectives The objective of this paper was to study the association between antenatal terbutaline and endotracheal intubation (ET) within the first 24 hours of life, RDS, bronchopulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH) in infants with the gestational age (GA) of Method This was a retrospective medical record review of preterm infants delivered at a single tertiary care center from October 2016 to December 2020. Multivariable logistic regression was used to explore the association between antenatal terbutaline and neonatal respiratory support. Result 1,794 infants were included, 234 (13.0%) had the GA of Conclusion In a state-of-the-art neonatal care setting, antenatal terbutaline was associated with a reduction in ET during the first 24 hours in infants with the GA of Key Points

The long-term use of adrenergic medication in treating various conditions, such as asthma, increases the chances of bone fracture. Dynamic mechanical loading at a specific time is a method for improving bone quality and promoting healing. Therefore, we hypothesized that precisely controlling the mechanical environment can contribute to the alleviation of the negative effects of chronic treatment with the common asthma drug terbutaline, which is a β2-adrenergic receptor agonist that facilitates bone homeostasis and defect repair through its anabolic effect on osteogenic cells. Our in vitro results showed that terbutaline can directly inhibit osteogenesis by impairing osteogenic differentiation and mineralization. Chronic treatment in vivo was simulated by administering terbutaline to C57BL/6J mice for 4 weeks before bone defect surgery and mechanical loading. We utilized a stabilized tibial defect model, which allowed the application of anabolic mechanical loading. During homeostasis, chronic terbutaline treatment reduced the bone formation rate, the fracture toughness of long bones, and the concentrations of bone formation markers in the sera. During defect repair, terbutaline decreased the bone volume, type H vessel, and total blood vessel volume. Terbutaline treatment reduced the number of osteogenic cells. Periostin, which was secreted mainly by Prrx1+ osteoprogenitors and F4/80+ macrophages, was inhibited by treating the bone defect with terbutaline. Interestingly, controlled mechanical loading facilitated the recovery of bone volume and periostin expression and the number of osteogenic cells within the defect. In conclusion, mechanical loading can rescue negative effects on new bone accrual and repair induced by chronic terbutaline treatment.

A simple and sensitive spectrophotometric method has been described for the assay of Salbutamol sulphate (SBS) and Terbutaline sulphate (TERS) in their pure and dosage forms. The method was based on the reaction of the nucleophilic compensation by interacting of drugs with the reagent 9-chloroacridine (9-CA) in basic medium. The products have absorption bands with maximum absorbance at 600 nm and 588 nm for SBS and TERS respectively. Beer’s law was obeyed in the range 0.5-12.0 μg.ml-1 and 0.1-6.0 μg.ml-1 with molar absorptivity values 1.913×104 and 1.0755×105 l.mol-1.cm-1, recoveries are 101.3% and 99.6% for above drugs respectively. The relative standard deviation (RSD) is less than 1.7% for both drugs. The probable reactions have been suggested.

Although tulobuterol tape is provided to patients in an inner package, information regarding the stability of the tape after opening the packaging may be requested by patients. This study was performed to generate underlying data on the storage stability after package opening or liner peeling with package opening. Tulobuterol tapes were stored at 25℃, 60% relative humidity (RH); 40℃, 75%RH; or in a refrigerator (2-4℃, 10-30%RH) for 1 day or 3 days. In a peel adhesive strength test after package opening, storage at 25℃, 60%RH had a low effect on the adhesive strength of the tape. Storage after liner peeling with package opening resulted in variable adhesive strength of the tape. Regarding drug release properties, for storage after package opening, the f2 values of tapes stored in the three different conditions were over 50, except for tapes stored at 25℃, 60%RH for 3 days. For the tapes stored at 25℃, 60%RH or 40℃, 75%RH after liner peeling with package opening, the release rate and the ratio of drug released at 24 h may be decreased because the drug content decreased due to drug sublimation. This study suggested that tulobuterol tapes can be stored after package opening at 25℃, 60%RH for 1 d.

Parenteral β-agonists are often used as adjuvant treatment for severe asthma exacerbations in pediatric patients. We wanted to determine if the addition of a single dose of parenteral terbutaline to our asthma protocol resulted in fewer pediatric intensive care unit (PICU) admissions. METHODS Patients were identified using a retrospective cohort analysis from a single, tertiary care, urban children's hospital. Patients presenting directly to our emergency department aged 2 to 18 years were included if they had a diagnosis of severe asthma exacerbation, defined by an initial Respiratory Clinical Score (RCS) of 9 or higher. A total of 787 patients were identified during the study timeframe (December 16, 2017, to December 31, 2018), and of those, 651 patients met study criteria and were included in the analysis. The χ test was used to establish P values for categorical variables. For normally distributed variables, a t test was used. For nonnormally distributed variables, the Kruskal-Wallis test was used. A P value of 0.05 or less was interpreted as statistically significant. RESULTS Patients who received terbutaline had an increased risk of admission to the PICU (P < 0.001). This association was lost after controlling for age, sex, continuous albuterol use, and intramuscular epinephrine use (P = 0.362). Patients receiving terbutaline in the emergency department also had a higher risk of admission to the hospital (odds ratio, 1.55; confidence interval, 1.08-2.22; P = 0.020) as compared with their nonterbutaline counterparts. Overall, patients in the terbutaline group had a higher initial RCS at presentation. Upon further analysis, patients with the same RCS at presentation were more likely to be admitted if they received terbutaline than those who did not. There was no statistically significant difference in length of stay (P = 0.298) and BiPAP/CPAP use (P = 0.107). The patients on terbutaline were relatively more likely to require oxygen (P = 0.003) and intramuscular epinephrine (P = 0.010) than the patients not on terbutaline. CONCLUSIONS Terbutaline administration given to pediatric patients experiencing a severe asthma exacerbation was not associated with decreased PICU or general hospital floor admission. The study is limited given that it was a retrospective analysis. Further randomized controlled trials are needed to assess the role of terbutaline in severe acute asthma exacerbations in pediatric patients.

Neonatal ventricular tachycardia (VT) is an extremely rare condition. We present a 35-week-old gestation neonate who developed tachycardia following maternal exposure to terbutaline. Upon transfer to our neonatal intensive care unit, an electrocardiogram (ECG) was obtained which was consistent with VT. The arrhythmia did not respond to vagal maneuvers or adenosine but resolved following cardioversion demonstrated on postcoversion ECG. At outpatient follow-up, the infant had no further episodes of arrhythmia. To the best of our knowledge, this represents the first case describing terbutaline-induced fetal or neonatal VT.

A 7-year-old female spayed dwarf rabbit ( Oryctolagus cuniculus ) was evaluated for respiratory distress 12 days after an ovariohysterectomy and mammary mass removal. Severe inspiratory stridor and open-mouth breathing were observed on presentation. Results of whole body radiographs revealed an intrathoracic tracheal stricture 12.5-cm distal to the nose. A 5-mm x 30-mm nitinol self-expanding metallic stent was placed under fluoroscopic guidance across the tracheal stricture. The patient was discharged the next day on a tapering course of prednisone over a week and a short course of a bronchodilator (terbutaline) and an antibiotic (enrofloxacin). On follow-up examinations from 10 days to 21 months after stent placement, no associated respiratory signs or stent complications were observed. At present, the rabbit remains otherwise healthy with an intact tracheal stent and no recurrent episodes of dyspnea over 24 months after placement. Tracheal stent placement in this rabbit allowed for emergent treatment of life threatening tracheal stricture formation utilizing a minimally invasive technique. Tracheal stenting resulted in rapid resolution of respiratory distress with favorable long term outcome. This is the first reported clinical case of tracheal stent use in a rabbit, and supports the tolerance of tracheal stents in this species long term.

While beta2 -adrenoceptor stimulation has been shown to increase lean mass and to alter metabolic properties of skeletal muscle, adaptations in muscle oxidative enzymes and maximal oxygen uptake ( V˙ O2max ) in response to beta2 -adrenergic agonist treatment are inadequately explored in humans, particularly in association with resistance training. Herein, we investigated beta2 -adrenergic-induced changes in V˙ O2max , leg and arm composition, and muscle content of oxidative enzymes in response to treatment with the selective beta2 -adrenergic agonist terbutaline with and without concurrent resistance training in young men. Forty-six subjects were randomized to 4 weeks of lifestyle maintenance (n = 23) or resistance training (n = 23). Within the lifestyle maintenance and resistance training group, subjects received daily terbutaline (8 × 0.5 mg) (n = 13) or placebo (n = 10) treatment. No apparent treatment by training interactions was observed during the study period. Terbutaline increased leg and arm lean mass with the intervention, whereas no treatment differences were observed in absolute V˙ O2max and incremental peak power output (iPPO). Treatment main effects were observed for V˙ O2 -reserve (P

The β2-adrenergic receptor (β2AR) is a membrane-bound G-protein-coupled receptor and an important drug target for asthma. Clinical studies report that the population variant Gln27Glu is associated with a differential response to common asthma drugs, such as albuterol, isoproterenol and terbutaline. Interestingly, the 27th amino acid is positioned on the N-terminal region that is the most flexible and consequently the least studied part of the receptor. In this study, we probe the molecular origin of the differential drug binding by performing structural modeling and simulations of the wild-type (Gln) and variant (Glu) receptors followed by ensemble docking with the ligands, albuterol, isoproterenol and terbutaline. In line with clinical studies, the ligands were observed to interact preferentially with the Glu variant. Our results indicate that the Glu residue at the 27th position perturbs the network of electrostatic interactions that connects the N-terminal region to the binding site in the wild-type receptor. As a result, the Glu variant is observed to bind better to the three ligands tested in this study. Our study provides a structural basis to explain the variable drug response associated with the 27th position polymorphism in the β2AR and is a starting step to identify genotype-specific therapeutics.

Summary Background In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide–formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline. Methods We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18–75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg–formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437. Findings Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide–formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide–formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48–1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide–formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed. Interpretation In adults with mild to moderate asthma, budesonide–formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid–formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma. Funding Health Research Council of New Zealand.

In this work, a novel sulfated-β-cyclodextrin (S-β-CD) coated stationary phase was prepared for open-tubular capillary electrochromatography (OT-CEC). The capillary was developed by attaching polydopamine/sulfated-β-cyclodextrin (PDA/S-β-CD) onto the gold nanoparticles (AuNPs) coated capillary which was pretreated with polydopamine. The results of scanning electron microscopy (SEM) and energy dispersive X-ray analysis spectroscopy (EDS) indicated that polydopamine/sulfated-β-cyclodextrin was successfully fixed on the gold nanoparticles coated capillary. To evaluate the performance of the prepared open tubular (OT) column, the enantioseparation was carried out by using ten chiral drugs as model analytes. Under the optimal conditions, salbutamol, terbutaline, trantinterol, tulobuterol, clorprenaline, pheniramine, chlorpheniramine, brompheniramine, isoprenaline and tolterodine were baseline separated with the resolution (Rs) values of 3.25, 1.76, 2.51, 1.89, 3.17, 2.17, 1.99, 1.72, 2.01 and 3.20, respectively. Repeatability of the column was studied, with the relative standard deviations for run-to-run, day-to-day and column-to-column lower than 5.7%.

Terbutaline is a prohibited drug except for athletes with a therapeutic use exemption certificate; terbutaline’s effects on endurance performance are relatively unknown. Purpose: To investigate the effects of 2 therapeutic (2 and 4 mg) inhaled doses of terbutaline on 3-km running time-trial performance. Methods: A total of 8 men (age 24.3 [2.4] y; weight 77.6 [8] kg; and height 179.5 [4.3] cm) and 8 women (age 22.4 [3] y; weight 58.6 [6] kg; and height 163 [9.2] cm) free from respiratory disease and illness provided written informed consent. Participants completed 3-km running time trials on a nonmotorized treadmill on 3 separate occasions following placebo and 2- and 4-mg inhaled terbutaline in a single-blind, repeated-measures design. Urine samples (15 min postexercise) were analyzed for terbutaline concentration. Data were analyzed using 1-way repeated-measures analysis of variance, and significance was set at P Results: No differences were observed for completion times (1103 [201] s, 1106 [195] s, 1098 [165] s; P = .913) for the placebo or 2- and 4-mg inhaled trials, respectively. Lactate values were higher (P = .02) after 4 mg terbutaline (10.7 [2.3] mmol·L−1) vs placebo (8.9 [1.8] mmol·L−1). Values of forced expiratory volume in the first second of expiration (FEV1) were greater after inhalation of 2 mg (5.08 [0.2]; P = .01) and 4 mg terbutaline (5.07 [0.2]; P = .02) compared with placebo (4.83 [0.5] L) postinhalation. Urinary terbutaline concentrations were mean 306 (288) ng·mL−1 and 435 (410) ng·mL−1 (P = .2) and peak 956 ng·mL−1 and 1244 ng·mL−1 after 2 and 4 mg inhaled terbutaline, respectively. No differences were observed between the male and female participants. Conclusions: Therapeutic dosing of terbutaline does not lead to an improvement in 3-km running performance despite significantly increased FEV1. The findings suggest that athletes using inhaled terbutaline at high therapeutic doses to treat asthma will not gain an ergogenic advantage during 3-km running performance.

Summary Objective The objective of the present work was to develop and validate a simple, sensitive, rapid and stable reverse-phase high performance liquid chromatography (RP-HPLC) method for a combination of Terbutaline sulphate (TSL), Ambroxol hydrochloride (AML) and Guaifenesin (GFN). Method The combination of these drugs was analyzed by using Shimadzu LC 2010 CHT high performance liquid chromatography (HPLC). Successful separation was achieved by isocratic elution on a reverse-phase C18 column (sun fire) (250 mm, 4.6 mm, 5 μ), using a mobile phase consisting of buffer: acetonitrile in the ratio 80: 20 (buffer − 0.1% v/v triethyleamine pH-3.0) followed by 1.0 mL/min flow rate. The wavelength of detection was at 220 nm. Result The chromatographic retention times were consistent at 3.0, 10.5 and 13.8 minutes for TSL, AML and GFN respectively. For these three compounds, the lower limit of detection was 1.0, 1.25, and 1.5 μg/mL and lower limit of quantification was 3.3, 4.1 and 5.0 μg/mL respectively. The linearity concentrations established for TSL, AML and GFN were 1.0–7.0, 1.5–7.5 and 4.0–14.0 μg/mL respectively. The correlation coefficients for all the drugs were found to be greater than 0.999. The relative standard deviation of inter- and intra-day were less than 2.0%. Conclusion This method provides a necessary tool for quantification of the selected drugs for their assay. The proposed method is simple, accurate, reproducible and applied successfully to analyze three compounds in pure as well dosage form.

Background:Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous preterm labour.Objective:We have reviewed the evidence concerning the safety and efficacy of various classes of tocolytic agents.Results:The evidence to support the use of magnesium sulfate or nitric oxide donors as a tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and β2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of β2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses.Conclusion:The perfect tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins.

BACKGROUND AND OBJECTIVE: Mixed inhaler device use for asthma is associated with worse inhaler technique and outcomes. Given that relievers are commonly prescribed as pressurized metred-dose inhalers (pMDI), changing preventers from dry powder inhalers (DPI) to pMDI may improve asthma outcomes. This study aimed to assess the persistence and effectiveness of switching from DPI to pMDI for inhaled corticosteroid and long-acting β2 -agonist combination therapy (ICS/LABA).METHODS: This was a historical cohort study using Ajou University Hospital (Korea) patient records. Persistence of switch was defined as receiving ≥1 pMDI and no DPI after the switch. Effectiveness of switch was assessed as the proportion without severe asthma exacerbation and the proportion achieving risk domain asthma control (RDAC; no asthma-related hospitalization, antibiotics without upper respiratory diagnosis or acute course of oral corticosteroids) and overall asthma control (OAC; RDAC and ≤ 200 μg salbutamol/≤500 μg terbutaline average daily dose) comparing 1 year after and before the switch.RESULTS: Within 85 patients who switched from DPI to pMDI and persisted for a year, higher proportion were free from asthma exacerbation after the switch (mean difference in proportion = 0.129, 95% CI: 0.038-0.220). Switching to pMDI was also associated with better RDAC (75.3% vs 57.7%, P = 0.001) and OAC (57.7% vs 45.9%, P = 0.021). From the entire 117 patients who switched to fixed-dose combination (FDC)/ICS LABA pMDI, 76.1% (95% CI: 69.0-100.0%) patients persisted in the following 6 months.CONCLUSION: Switching to and persisting with pMDI was associated with decreased asthma exacerbations and improved asthma control. The majority of patients persisted with the switch to pMDI for ICS/LABA treatment.

Astragalus membranaceus may be a potential therapy for childhood asthma but its driving mechanism remains elusive. The main components of A. membranaceus were identified by HPLC. The children with asthma remission were divided into two combination group (control group, the combination of budesonide and terbutaline) and A. membranaceus group (treatment group, the combination of budesonide, terbutaline and A. membranaceus). The therapeutic results were compared between two groups after 3-month therapy. Porcine peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by using density gradient centrifugation on percoll. The levels of FoxP3, EGF-β, IL-17 and IL-23 from PBMCs and serum IgE were measured. The relative percentage of Treg/Th17 cells was determined using flow cytometry. The main components of A. membranaceus were calycosin-7-O-glucoside, isoquercitrin, ononin, calycosin, quercetin, genistein, kaempferol, isorhamnetin and formononetin, all of which may contribute to asthma therapy. Lung function was significantly improved in the treatment group when compared with a control group (P < 0.05). The efficacy in preventing the occurrence of childhood asthma was higher in the treatment group than the control group (P < 0.05). The levels of IgE, IL-17 and IL-23 were reduced significantly in the treatment group when compared with the control group, while the levels of FoxP3 and TGF-β were increased in the treatment group when compared with the control group (P < 0.05). A. membranaceus increased the percentage of Treg cells and reduced the percentage of Th17 cells. A. membranaceus is potential natural product for improving the therapeutic efficacy of combination therapy of budesonide and terbutaline for the children with asthma remission by modulating the balance of Treg/Th17 cells.

Intrauterine inflammation generates inflammatory mediators that damage the developing bronchoalveolar epithelium, resulting in neonatal lung injury. Lung fluid transport disorders are the main reasons for the development of pulmonary edema, an important pathology of lung injury. Previous studies suggested that epithelial sodium channels (ENaCs) play an important role in lung fluid transport. Here, we investigated whether changes in the expression of ENaCs were observed when neonatal rat lung injury was induced by maternal exposure to endotoxin. We also examined the therapeutic effect of terbutaline nebulizer inhalation on this injury. The results showed that maternal exposure to endotoxin increased the levels of TNF‐α and IL‐1β in bronchoalveolar lavage fluid, suppressed α‐, β‐, γ‐ENaC in the neonatal rat lung, and resulted in the formation of pulmonary edema on postnatal days 1 and 7. Terbutaline up‐regulated the expression of β‐ and γ‐ENaC in the distal lung after 7 days of treatment. The potential signal molecules cAMP, PKA, and CREB expressions were increased after terbutaline treatment. In summary, maternal exposure to endotoxin decreased the expression of ENaCs in neonatal rats which, in turn, may exacerbate pulmonary edema. Inhalation of the β2‐adrenergic receptor agonist terbutaline improved lung liquid clearance. By increasing the expression of sodium ion channels, the effective removal of alveolar fluid provides a new way for the prevention and treatment of neonatal lung injury.

The present study describes two stability-indicating HPLC methods with two different chromatographic approaches for the simultaneous estimation of bambuterol and its main degradation product, terbutaline in bulk and pharmaceuticals. Method I was carried out using a conventional particle-packed cyano column (150 mm × 4.6 mm, 5 μm particle size) and a micellar eluent composed of 0.1 M SDS, 15% n-propanol, and 0.3% triethylamine (pH 3.5), coupled with UV detection at 220 nm. Method II was based on the fused core shell technology, and the separation was carried out using a Kinetex C18 column (150 mm × 4.6 mm, 5 μm particle size) and an aqueous mobile phase composed of methanol and a 0.1 M phosphate buffer (45 : 55 v/v; pH 4), using fluorescence detection at λex = 275 nm and λem = 313 nm. The first method was rectilinear over the concentration range of 10–200 μg mL−1 for bambuterol and 5–100 μg mL−1 for terbutaline while the second method showed a good linearity in the range of 1–5 μg mL−1 for bambuterol and 0.1–1 μg mL−1 for terbutaline. The developed methods enabled the quantification of bambuterol and terbutaline in their dosage forms, including tablets and syrups and showed good results compared to the official methods. The practical and analytical comparisons between the two proposed methods is discussed.

Background Preterm birth is the most common cause of neonatal morbidity and mortality. Tocolytics are considered a standard treatment for women with threatened preterm delivery to allow time for maternal steroid administration and transfer to referral centers with neonatal intensive care units. However, there is controversy about the best tocolytic therapy to be considered as the first choice. The aim of this study is to compare the tocolytic effectiveness and tolerability of combination therapy with nifedipine and indomethacin versus nifedipine monotherapy among Sudanese women with preterm labor (PTL) as well as to compare the possible neonatal outcomes associated with each drug. Methods/design This is a randomized controlled clinical trial to be conducted in the Medani Maternity Hospital, Sudan. Women aged 18–40 years that are diagnosed with preterm labor and have a gestational age between 25 and 34 weeks will be eligible to participate in this trial. The diagnosis of threatened PTL is defined as persistent uterine contractions “(four contractions every 20 min or eight contractions every 60 min)” with cervical changes “(cervical effacement ≤80% or cervical dilatation >two cm)”. Patients will be eligible regardless of the presentation of the fetus. It will be randomly decided whether participants receive nifedipine/indomethacin combination therapy or nifedipine monotherapy. The primary outcome is the number of women who do not deliver and do not need alternative tocolytic drug (terbutaline). The secondary outcome is an estimated association with neonatal morbidity and mortality. The sample size will be 117 subjects in each arm of the study, according to a type I error of 0.05 and a study power of 80%. Discussion We expect higher effectiveness of the combination indomethacin/nifedipine tocolytic therapy compared with nifedipine monotherapy. We plan to suggest this combination therapy as the best option for postponing PTL. Trial registration Clinical trial registration: PACTR202004681537890, date of registration: March 8, 2020.

Objective In vivo studies have reported several beneficial metabolic effects of β-adrenergic receptor agonist administration in skeletal muscle, including increased glucose uptake, fatty acid metabolism, lipolysis and mitochondrial biogenesis. Although these effects have been widely studied in vivo, the in vitro data are limited to mouse and rat cell lines. Therefore, we sought to discover the effects of the β2-adrenergic receptor agonist terbutaline on metabolism and protein synthesis in human primary skeletal muscle cells. Methods Human cultured myotubes were exposed to terbutaline in various concentrations (0.01–30 ​μM) for 4 or 96 ​h. Thereafter uptake of [14C]deoxy-D-glucose, oxydation of [14C]glucose and [14C]oleic acid were measured. Incorporation of [14C]leucine, gene expression by qPCR and proteomics analyses by mass spectrometry by the STAGE-TIP method were performed after 96 ​h exposure to 1 and 10 ​μM of terbutaline. Results The results showed that 4 ​h treatment with terbutaline in concentrations up to 1 ​μM increased glucose uptake in human myotubes, but also decreased both glucose and oleic acid oxidation along with oleic acid uptake in concentrations of 10–30 ​μM. Moreover, administration of terbutaline for 96 ​h increased glucose uptake (in terbutaline concentrations up to 1 ​μM) and oxidation (1 ​μM), as well as oleic acid oxidation (0.1–30 ​μM), leucine incorporation into cellular protein (1–10 ​μM) and upregulated several pathways related to mitochondrial metabolism (1 ​μM). Data are available via ProteomeXchange with identifier PXD024063. Conclusion These results suggest that β2-adrenergic receptor have direct effects in human skeletal muscle affecting fuel metabolism and net protein synthesis, effects that might be favourable for both type 2 diabetes and muscle wasting disorders., Graphical abstract Image 1, Highlights • The metabolic effects of terbutaline were studied in human primary myotubes. • Acute treatment with terbutaline increased glucose uptake. • Chronic treatment with terbutaline increased glucose and oleic acid oxidation. • Chronic treatment with terbutaline increased protein synthesis. • Proteomics analysis revealed an increase in mitochondrial proteins.

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.

Experimental data have suggested that in neuropathic pain, tricyclic antidepressants may work solely through a β2-agonist action. The aim of this study was to test if the β2-agonist terbutaline relieves painful polyneuropathy. The study was a randomized, double-blind, placebo-controlled and active-controlled, 3-way, cross-over trial among patients with painful polyneuropathy. The treatment periods were of 5 weeks' duration and were preceded by 1 week for washout and 1 week for baseline observations. The patients received terbutaline (5-15 mg), imipramine (30-150 mg), or placebo in a random order. Drug doses depended on age and metabolizer status. The change in total pain recorded from ratings in diaries (numeric rating scale [NRS] 0-10) was the primary outcome, and the change in rating of specific pain symptoms (NRS 0-10), patient global impression of change, and sleep disturbance were secondary outcomes. Forty-seven patients were randomized. The median score for total pain changed from NRS 6.4 to 6.1 from baseline to week 5 on terbutaline with an average effect during the treatment period as compared with placebo of 0.13 (95% confidence interval -0.12 to 0.38, P = 0.32). The median score for total pain on imipramine changed from NRS 6.6 to 4.8 with an average effect as compared with placebo of -1.17 (95% confidence interval -1.42 to -0.92, P < 0.001). Secondary outcomes were also unaltered by terbutaline but improved by imipramine. The β2-agonist terbutaline has no effect in painful polyneuropathy. β2-agonism seems not to be an important mechanism of action of tricyclic antidepressants in neuropathic pain.

INTRODUCTION Recent pharmaceutical shortages in continuous inhaled β-agonist medications forced us to look at alternative uses of currently available medications for the treatment of acute asthma exacerbations. We elected to recommend a single dose of subcutaneous terbutaline as adjuvant therapy to our current treatment algorithm for severe acute asthma exacerbation at our hospital. PATIENTS AND METHODS Patients were identified using a retrospective cohort analysis from a single quaternary urban children’s hospital. Patients age 2 to 18 years old were included …

The aim of this study was to compare the clinical efficacy of azithromycin and ceftizoxime (AC) and erythromycin and amoxicillin/sulbactam (EAS) in the treatment of children with Mycoplasma pneumoniae pneumonia (MPP). In this retrospective study, a total of 92 eligible children with MPP were included, and they were divided into a treatment group (n = 46) and a control group (n = 46). All patients were treated with intravenous ambroxol, and nebulized inhalation of budesonide and terbutaline. In addition, patients in the treatment group received AC. Patients in the control group underwent EAS. All patients in both groups were treated for a total of 10 days. Outcomes consist of erythrocyte sedimentation rate, C-reactive protein, serum lactate dehydrogenase, and interleukin 6, fever clearance time, time of cough disappearance, time of rale disappearance, time of signs disappeared by X-ray, and adverse events. All outcomes were measured after 10-day treatment. After treatment, patients who received AC exerted better improvements in erythrocyte sedimentation rate (P

Effective tocolysis is essential after fetal myelomeningocele repair and is associated with the development of pulmonary edema. The increased uterine activity in the immediate postoperative period is commonly treated with magnesium sulfate. However, other tocolytic agents such as nitroglycerine, nifedipine, indomethacin, terbutaline, and atosiban (outside the US) have also been used to combat uterine contractility. The ideal tocolytic regimen which balances the risks and benefits of in-utero surgery has yet to be determined. In this case report, we describe a unique case of fetal myelomeningocele repair complicated by maternal pulmonary edema and increased uterine activity resistant to magnesium sulfate therapy.

Introduction Budesonide-formoterol taken as needed is an emerging treatment for mild asthma. Objective We used data from the SYGMA studies to assess the safety of As-needed budesonide-formoterol compared with As-needed terbutaline and compared with maintenance budesonide. Methods SYGMA 1 and 2 were 52-week, double-blind, parallel-group studies in patients aged ≥ 12 years with physician-assessed mild asthma. Patients were randomized to As-needed budesonide-formoterol 200/6 μg, twice-daily budesonide 200 μg as maintenance plus As-needed terbutaline 0.5 mg, and As-needed terbutaline 0.5 mg (SYGMA 1 only). Adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs (DAEs), and study-defined asthma-related discontinuations from corresponding treatment groups in both studies were pooled. SYGMA 1 data were used for comparisons with As-needed terbutaline alone. Results The pooled analysis included 3366 patients in the As-needed budesonide-formoterol group and 3369 in the budesonide maintenance group, with AEs in 40.8% and 42.5% of patients, respectively. Common AEs included viral upper respiratory tract infection (viral URTI) and URTI. SAE, DAE, and asthma-related discontinuation rates were similar with As-needed budesonide-formoterol and maintenance budesonide. Potential local and systemic corticosteroid class effects were reported in ≤ 1% of patients for each budesonide-containing regimen. In SYGMA 1, AEs were more common in the As-needed terbutaline (n = 1277) than As-needed budesonide-formoterol (n = 1277) groups (42.7 vs. 38.0%), as were DAEs (2.9 vs. 0.8%) and asthma-related discontinuations (1.6 vs. 0.3%). Conclusions Budesonide-formoterol anti-inflammatory reliever therapy is generally well-tolerated in patients with mild asthma and has a safety profile similar to that of daily budesonide. No new safety signals were identified. ClinicalTrial.gov Identifiers NCT02149199 (SYGMA 1) and NCT02224157 (SYGMA 2). Supplementary Information The online version contains supplementary material available at 10.1007/s40264-020-01041-z.

An 11-year-old, domestic short-haired cat presented out-of-hours with a 1-day history of dyspnoea and open-mouthed breathing. Ninety minutes after arrival, the cat acutely deteriorated. Butorphanol (0.2 mg/kg) was administered intravenously via a preplaced cephalic vein cannula, after which anaesthesia was induced (1.3 mg/kg alfaxalone). The cat’s trachea was intubated with a 3.5 mm internal diameter cuffed endotracheal tube (ETT), but it was not possible to give a manual breath and a capnograph trace was absent; therefore the ETT was replaced with a 4.5 mm internal diameter cuffed ETT. A manual breath was still not possible but a capnograph trace was present (end-tidal carbon dioxide tension of 95 mmHg (12.7 kPa)). Intravenous dexamethasone (0.15 mg/kg) and terbutaline (0.01 mg/kg) were administered. Computed tomography revealed a heart base mass compressing the trachea and decreasing its lumen to 1 mm diameter. The cat was euthanased due to poor prognosis. Histopathology revealed a chemodectoma.

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 β2-adrenergic (β2AR) 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 β2AR 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.

Introduction: The SYGMA 1 & 2 trials (NCT02149199; NCT02224157) showed as-needed budesonide/formoterol (BUD/FORM) was comparable to BUD maintenance in reducing exacerbation risk in mild asthma. Aim: To examine the efficacy of as-needed BUD/FORM and BUD maintenance for severe exacerbations using pooled data from SYGMA 1 & 2. Methods: Mild asthma patients were randomised to placebo twice daily (bid) + as-needed BUD/FORM 200/6 µg (n=3366) or BUD 200 µg bid + as-needed terbutaline (BUD maintenance; n=3369). Treatment adherence, number and rate of severe exacerbations, time to first severe exacerbation and inhaled ICS load data were compared for these two treatments. Results: Mean maintenance adherence was 69.7% and 69.0% for as-needed BUD/FORM and BUD maintenance arms, respectively. As-needed BUD/FORM was comparable to BUD maintenance in number of severe exacerbations (294 vs 310), proportion of patients with severe exacerbations (7.4% vs 7.8%), as well as annual rate (0.096 vs 0.104; RR 0.93 [0.77, 1.11]; p=0.408) and time to first severe exacerbation (HR 0.94 [0.79, 1.12]; p=0.463) (figure). Total median daily ICS delivered dose was 78% lower with as-needed BUD/FORM (51.8 µg) compared with BUD maintenance (240.2 µg). Conclusions: In mild asthma, as-needed BUD/FORM provided comparable efficacy in reducing the risk of severe exacerbation to BUD maintenance with only 22% of the total median daily ICS dose.

Summary Background In mild asthma, as-needed budesonide–formoterol reduces long-term exacerbation risk compared with as-needed short-acting β2-agonist (SABA), with a similar or increased reduction versus maintenance with budesonide plus as-needed SABA, despite a lower budesonide dose. In this post-hoc analysis of the SYmbicort Given as needed in Mild Asthma (SYGMA) 1 study, we investigated the short-term risk of severe exacerbations after a single day with various levels of reliever use. Methods SYGMA 1 was a 52-week, double-blind, randomised, controlled, phase 3 trial, in which patients aged 12 years or older with mild asthma were randomly assigned (1:1:1) to placebo twice daily plus as-needed terbutaline 0·5 mg, placebo twice daily plus as-needed budesonide–formoterol 200–6 μg, or budesonide 200 μg twice daily plus as-needed terbutaline (ie, budesonide maintenance group). In this post-hoc analysis, we assessed the frequency of reliever use and the risk of a severe exacerbation in the 21 days after first use of more than two, four, six, or eight reliever inhalations in 24 h. SYGMA 1 is registered with ClinicalTrials.gov , NCT02149199 , and is now complete. Findings Of 5721 patients enrolled in SYGMA 1, 3849 were randomly assigned to as-needed terbutaline (n=1280), as-needed budesonide–formoterol (n=1279), or budesonide maintenance (n=1290), of whom 3836 had evaluable data (n=1277 as-needed terbutaline, n=1277 as needed budesonide–formoterol, and n=1282 budesonide maintenance). Median reliever use was 0·32 (IQR 0·08–0·91) inhalations per day for the as-needed terbutaline group, 0·29 (0·07–0·72) for the as-needed budesonide–formoterol group, and 0·16 (0·04–0·52) for the budesonide maintenance group. Compared with as-needed terbutaline, after adjustment for age, sex, randomly assigned treatment, pre-study treatment group, baseline % predicted post-bronchodilator FEV1, and severe exacerbation in the 12 months before enrolment in the study, the hazard ratio (HR) for severe exacerbation in the 21 days after a single day with more than two as-needed inhalations was 0·27 (95% CI 0·12–0·58; p=0·0008) with as-needed budesonide–formoterol and 0·39 (0·19–0·79; p=0·0091) with budesonide maintenance; after a single day of more than four as-needed inhalations the HR was 0·24 (0·10–0·62; p=0·0030) with as-needed budesonide–formoterol and 0·30 (0·13–0·72; p=0·0065) with budesonide maintenance; and after a single day of more than six as-needed inhalations the HR was 0·14 (0·02–1·06; p=0·057) with as-needed budesonide–formoterol and 0·43 (0·14–1·26; p=0·12) with budesonide maintenance. HRs were not calculated for more than eight as-needed inhalations due to the small number of events. Interpretation In mild asthma, as-needed budesonide–formoterol reduces the short-term risk of severe exacerbations after a single day of higher use (more than two as-needed inhalations), even when overall use is infrequent. Use of an anti-inflammatory reliever might reduce the risk of short-term severe exacerbations by the timely provision of increased doses of as-needed inhaled corticosteroids and formoterol when symptoms occur. These findings should be further assessed in prospective randomised clinical trials. Funding AstraZeneca.

The objective of this study was to develop a simpler and more practical quantitative evaluation method of cold flow (CF) in transdermal drug delivery systems (TDDSs). CF was forcibly induced by loading a weight on a punched-out sample (bisoprolol and tulobuterol tapes). When the extent of CF was analyzed using the area of oozed adhesive as following a previously reported method, the CF profiles were looked different between the samples 12 mm in diameter subjected to a 0.5-kg weight and samples 24 mm in diameter subjected to a 2.0-kg weight despite an equal load per unit area (4.42 g/mm2). The width of oozed adhesive around the original sample was suggested to be an index that properly describes the relationship between the load per unit area and the extent of CF. Further, it was clarified that the average CF width over the entire circumference of the sample was the same whether the samples were round or square as long as the sample area and load were the same. We also observed a linear relationship between the CF width and the aspect ratio of oval and rectangular samples. These results indicated that the CF properties of typical TDDS products lacking CF-proof processing at the edges could be determined by testing samples cut from the product rather than the whole TDDS patch. The proposed width measuring method was simple and useful for optimizing the composition of the adhesive and for testing the quality of the product.

NEW FINDINGS What is the central question of this study? What is the role of β2 -adrenergic receptor (β2 AR) vasodilatation in older postmenopausal women as compared to premenopausal women and the role of nitric oxide (NO) in β2 AR-mediated vasodilatation in both groups of women? What is the main finding and its importance? β2 AR responsiveness is blunted in postmenopausal women compared to young premenopausal women. Additionally, NO may contribute to β2 AR-mediated vasodilatation in young premenopausal women. ABSTRACT β2 -Adrenergic receptor (β2 AR)-mediated vasodilatation, which is partially dependent on nitric oxide (NO) formation, is blunted in men at risk for developing hypertension. However, the role of β2 AR vasodilatation in hypertension pathophysiology in ageing postmenopausal women is unclear. Therefore, the goals of this study were to determine if forearm vasodilatation to the selective β2 AR agonist terbutaline is blunted in older postmenopausal women (59 ± 4 years) compared to young premenopausal women (27 ± 3 years) and to assess NO contribution to β2 AR-mediated vasodilatation in both groups of women. Forearm blood flow (FBF) and forearm vascular conductance (FVC) were measured using venous occlusion plethysmography at baseline and during intra-arterial infusions of terbutaline at 0.1-2.0 µg (100 ml tissue)-1 min-1 with and without the NO synthase inhibitor l-NG -monomethylarginine (l-NMMA). Mean arterial pressure was significantly greater in postmenopausal women than in young women at baseline (P = 0.01). Baseline FBF and FVC did not differ between young and postmenopausal women (P > 0.05) and rose significantly within each group during terbutaline infusion (P 0.05 for all). These data suggest that β2 AR responsiveness is blunted in postmenopausal women compared to young premenopausal women, and that NO may contribute to β2 AR-mediated vasodilatation in young premenopausal women.

Patient: Male, 16-year-old Final Diagnosis: Priapism Symptoms: Erectile Medication: Propofol Clinical Procedure: Catheter ablation Specialty: Cardiology Objective: Diagnostic/therapeutic accidents Background: Priapism is rarely reported as a potential complication after the cardiac ablation procedure. We report the case of a teenager admitted for atrial flutter ablation who developed priapism following the procedure. Case Report: A 16-year-old male with episodic atrial flutter came to our hospital for an electrophysiological study and catheter ablation. During the procedure, he was given IV propofol for anesthesia and IV heparin for anticoagulation. After the procedure, nursing noted that he had an erection, which persisted for 5 h, with complaints of discomfort. There was no known history of sickle cell disease or trauma to the perineum, nor did he endorse any prior prolonged erections. On physical examination, he had a circumcised phallus with rigid and non-tender corpora cavernosa. He was given 5 mg terbutaline PO, without improvement. Three hours later, a second dose of terbutaline was given. In addition, a penis corporal venous blood gas was taken, and the result was consistent with an ischemic priapism. He had detumescence 1–2 min later. The total duration of his priapism was 8 h. There was no swelling, pain, or any sequelae after detumescence. Conclusions: Although priapism rarely occurs as a complication following catheter ablation procedures due to propofol use, prolonged priapism can result in corporal fibrosis and cause future erectile dysfunction. Recognition and treatment of priapism in the postoperative period may be delayed due to a patient’s hesitance to express concerns. To prevent future erectile dysfunction, signs of priapism should be included in routine postoperative evaluation in male patients.

A four-year-and-three-month-old Jack Russell terrier presented for investigation of acute-onset paraplegia, with an MRI performed under general anaesthesia. Following administration of a gadobutrol contrast medium, apnoea, cyanosis, resistance to ventilation, hypotension and tachycardia were observed. An anaphylactic reaction was suspected, characterised by severe bronchoconstriction and cardiovascular collapse. This was treated with multiple isotonic crystalloid fluid boluses, intermittent positive pressure ventilation, terbutaline and cessation of general anaesthesia. Following recovery from general anaesthesia, continuous positive airway pressure and later high-flow nasal oxygen therapy were needed to treat severe hypoxaemia. Treatment of the acute anaphylactic reaction was successful; however, the dog was euthanased due to progressive neurological disease.

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

BACKGROUND AND OBJECTIVE Terbutaline is a β-agonist that used as growth promoters to improved carcass chemical composition of chicks without residues. The purpose of the present investigation is exploring the effect of different dietary levels and duration of terbutaline on the productive performance, biochemical and carcass quality traits including residue of acres broiler. MATERIALS AND METHODS A total of 150 one-day-old arbor acres broiler chicks were allotted into 5 groups (3 replicates per each). Group 1 was fed on the basal diet without supplement, while groups 2-5 fed on the basal diet supplemented by 5 or 10 mg terbutaline kg-1 diet during 1-42 or 21-42 days, respectively. RESULTS When handling the dietary levels and duration of terbutaline, results of the present study showed that10 mg terbutaline kg-1 diet during the whole experimental period is a more effective dose for improvement of growth performance with significant (p

Humic substances (HS) play an important role in the phototransformation of micro-pollutants in surface waters and a significant part of this reactivity is often attributed to oxidant triplet excited states (3HS*). The present study aims to understand why 3HS* were found to be negligibly involved in the HS-mediated phototransformation of β2-adrenoceptor agonist terbutaline (TBL) while this chemical shows a high reactivity towards triplet 3-carboxybenzophenone (3CBP*), a typical HS model sensitizer. To clarify this apparent discrepancy, several experiments were conducted. We first confirmed that TBL can be easily oxidized by triplet riboflavin (3RF*), another sensitizer (k = (1.7 ± 0.4) × 109 M−1 s−1). Afterwards, we studied the effect of TBL on the HS-mediated phototransformation of 2,4,6-trimethylphenol (TMP), chosen for its high reactivity with 3HS*. TBL was found to enhance the rate of TMP loss. This result is rationalized by postulating that (i) TMP and TBL are both oxidized by 3HS* to yield the phenoxyl radicals TMP-H• and TBL-H•, respectively, and (ii) TBL-H• is further reduced by TMP which generates additional TMP-H•. Fitting the experimental data gives k = (1.8 ± 0.5) × 109 M−1 s-1 for the reaction between 3HS* and TBL and DFT calculations further support the conclusion that TBL-H• can be reduced by a lot of phenols. Hence, in the case of TBL, the oxidant effect of 3HS* is counterbalanced by the antioxidant properties of HS.