Terbutaline Infusion Research Articles

Forearm vasodilatation to a β2 -adrenergic receptor agonist in premenopausal and postmenopausal women.

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. 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±4years) compared to young premenopausal women (27±3years) 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 0.1-2.0µg (100ml 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). There were significant group × dose interactions for FBF (P=0.01) and FVC (P=0.001), indicating vasodilator responses were lower in postmenopausal women. In young women, FVC response to the highest dose of terbutaline tended to be lower with l-NMMA co-infusion vs. without l-NMMA (P=0.05). There were no significant decreases in FBF or FVC responses to terbutaline in postmenopausal women with l-NMMA co-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.

β2-Agonist Induces Net Leg Glucose Uptake and Free Fatty Acid Release at Rest but Not During Exercise in Young Men.

The role of selective β2-adrenergic stimulation in regulation of leg glucose uptake and free fatty acid (FFA) balance is inadequately explored in humans. The objective of this study was to investigate β2-adrenergic effects on net leg glucose uptake and clearance, as well as FFA balance at rest and during exercise. The study was a randomized, placebo-controlled crossover trial where 10 healthy men received either infusion of β2-agonist terbutaline (0.2 to 0.4 mg) or placebo. Net leg glucose uptake and clearance and FFA balance were determined at rest and during 8 minutes of knee extensor exercise using Fick's principle. Vastus lateralis muscle biopsies were collected at rest and at cessation of exercise. The primary outcome measure was net leg glucose uptake. At rest, net leg glucose uptake and clearance were 0.35 (±0.16) mmol/min and 41 (±17) mL/min (mean ± 95% CI) higher (P < 0.001) for terbutaline than placebo, corresponding to increases of 84% and 70%. During exercise, no treatment differences were observed in net leg glucose uptake, whereas clearance was 101 (±86) mL/min lower (P < 0.05) for terbutaline than placebo. At rest, terbutaline induced a net leg FFA release of 21 (±14) µmol/min, being different from placebo (P = 0.04). During exercise, net leg FFA uptake was not different between the treatments. These observations indicate that β2-agonist alters net leg glucose uptake and clearance, as well as FFA balance in humans, which is associated with myocellular β2-adrenergic and insulin-dependent signaling. Furthermore, the study shows that exercise confounds the β2-adrenergic effect on net leg glucose uptake and FFA balance.

Safety of Terbutaline for Treatment of Acute Severe Pediatric Asthma.

The use of continuous intravenous terbutaline treatment in severe asthma attacks has been hampered by the lack of well-powered clinical trials where effects of such treatment are described in detail. Here, we aimed to provide a descriptive report on the largest cohort of severe pediatric asthma patients treated with terbutaline. The study was conducted in a pediatric intensive care unit in a large metropolitan tertiary care university hospital on 124 patients receiving terbutaline infusion. To stratify the effect of, and determine any age-related differences of, terbutaline, the patients were divided into 3 age groups (0-6 years, 7-12 years, and 13-18 years). Clinical response and the potential harmful effects of terbutaline infusion were determined. There were significant reductions in systolic (varying between 86% and 93% of the baseline) and diastolic blood pressures (varying between 74% and 86% of the baseline level). However, the values returned to baseline level shortly after discontinuation of infusion. Terbutaline increased heart rates in all groups shortly after initiation (9%-13% above baseline), which returned to below baseline levels 1 hour after discontinuation. Serum potassium levels were also reduced in all patients compared to their baseline values after initiation of terbutaline infusion. However, none of the subjects required potassium replacement. The results indicate that overall, terbutaline infusion was well tolerated without irreversible adverse effects of the treatment. Although hemodynamic and metabolic disturbances occurred, these were clinically easily managed and posed little risk in emergency department or pediatric intensive care unit.

Continuous Low Dose Terbutaline Infusion as Maintenance Therapy to Reduce Preterm Births: A Reappraisal

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Effect of adrenergic agonists on coronary blood flow: a laboratory study in healthy volunteers.

Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α‐adrenergic receptors and β‐adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone. The purpose of this laboratory study was to noninvasively quantify coronary responses to adrenergic receptor stimulation in humans. Fourteen healthy volunteers (11 men and 3 women) performed isometric handgrip exercise to fatigue followed by intravenous infusion of isoproterenol. A subset of individuals also received infusions of phenylephrine (n = 6), terbutaline (n = 10), and epinephrine (n = 4); all dosages were based on fat‐free mass and were infused slowly to achieve steady‐state. The left anterior descending coronary artery was visualized using Doppler echocardiography. Beat‐by‐beat heart rate (HR), blood pressure (BP), peak diastolic coronary velocity (CBVpeak), and coronary velocity time integral were calculated. Data are presented as M ± SD. Isometric handgrip elicited significant increases in BP, HR, and CBVpeak (from 23.3 ± 5.3 to 34.5 ± 9.9 cm/sec). Isoproterenol raised HR and CBVpeak (from 22.6 ± 4.8 to 43.9 ± 12.4 cm/sec). Terbutaline and epinephrine evoked coronary hyperemia whereas phenylephrine did not significantly alter CBVpeak. Different indices of coronary hyperemia (changes in CBVpeak and velocity time integral) were significantly correlated (R = 0.803). The current data indicate that coronary hyperemia occurs in healthy humans in response to isometric handgrip exercise and low‐dose, steady‐state infusions of isoproterenol, terbutaline, and epinephrine. The contribution of β1 versus β2 receptors to coronary hyperemia remains to be determined. In this echocardiographic study, we demonstrate that coronary blood flow increases when β‐adrenergic receptors are stimulated (i.e., during exercise and different intravenous infusions). Our infusion paradigms and beat‐by‐beat imaging methodologies can be used in future studies to evaluate age‐, sex‐, and disease‐ differences in adrenergic control of coronary blood flow.

Continuous terbutaline infusion in severe asthma in adults: a retrospective study of long-term efficacy and safety

Background: Long-term subcutaneous or intravenous infusion of terbutaline has been used to stabilize asthma in patients enduring frequent hospital admissions due to severe asthma despite maximum therapy. However, this treatment is not supported by significant body of evidence. Aim: To study long-term efficacy and safety of using continuous infusions of terbutaline in unstable severe asthma. Methods: The available medical records of all patients received terbutaline infusions at a severe asthma unit between 1982 and 2008 were retrospectively studied. We retrieved data on treatment indication, asthma subtype, patient demographics, pre-treatment terbutaline trial outcome, duration of treatment, effect on lung function, hospital admissions, oral corticosteroids (OCSs) requirement, safety and side effects. Results: Forty-two patients with adequate medical information were studied (31 females, mean age 43.6 years, 88% had type 1 brittle asthma and 12% had other severe asthma). This group of patients had a mean body mass index of 30.8 kg/m2, mean oral prednisolone or equivalent of 26.6 mg and mean predicted FEV1 of 66.8%. The mean treatment duration was 86.7 months (range 7–216). Long-term continuous terbutaline infusion significantly reduced hospital admissions (mean pre-treatment = 6.7 (95% CI 0.96–12.4) per annum, and mean annualized on-treatment admission = 3.3 (95% CI 0.63–6.9, p = 0.045). We observed overall reduction in OCSs use in 59% of patients with available data, but there was no significant change in lung function. Side effects related to terbutaline or the method of its infusion were common and some were serious especially when central venous access device were used. Conclusion: Continuous terbutaline infusion could be a treatment option for severe unstable asthma and may reduce hospital admissions. However, the treatment was associated with significant side effects and its use should be limited to centers possessing necessary expertise.

Early administration of terbutaline in severe pediatric asthma may reduce incidence of acute respiratory failure

BackgroundSevere pediatric asthma, if not immediately and aggressively treated, may progress to acute respiratory failure requiring mechanical ventilation in the pediatric intensive care unit (PICU). Intravenous (IV) terbutaline, a β2 agonist, is dispensed when the initial treatment does not improve the clinical condition. ObjectiveTo investigate the influence of early initiation of IV terbutaline on the incidence of acute respiratory failure requiring mechanical ventilation in severe pediatric asthma. MethodsA retrospective chart review was conducted of 120 subjects (35 patients from an outside hospital emergency department [ED] with late start of terbutaline and 85 patients from the authors' hospital ED with early initiation of IV terbutaline) admitted to the PICU with severe asthma treated with continuous IV terbutaline. Responses to terbutaline treatment and outcomes were evaluated. ResultsPatients transported from outlying hospital EDs had shorter pre-PICU mean durations of IV terbutaline than those transferred from the authors' ED (0.69 ± 1.38 and 2.91 ± 2.47 hours, respectively, P = .001). Twenty-one of 35 patients (60%) from outlying EDs required mechanical ventilation compared with 14 of 85 patients (16%) from the authors' ED (P = .001). Durations of pre-PICU terbutaline infusion for patients requiring mechanical ventilation were significantly shorter than those with no such requirement (P = .015). ConclusionThe results of the present study, conducted in the largest number of subjects to date, suggest that early administration of continuous terbutaline in the ED may decrease acute respiratory failure and the need for mechanical respiratory (invasive and noninvasive) support in severe pediatric asthma.

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Introduction: Isoflurane is conventionally used for general anesthesia, but also has a well-documented off-label use as a bronchodilator for the treatment of severe, refractory status asthmaticus. Several cases have been described in the medical literature in which patients receiving prolonged isoflurane therapy for asthma have experienced untoward neurologic side effects. To our knowledge, there are no documented cases of bilateral fixed and dilated pupils secondary to isoflurane therapy in critically-ill children. We report this condition in two asthmatic patients who received isoflurane. Case One: An 8 year-old male with past history of asthma was admitted to the pediatric intensive care unit in respiratory distress secondary to status asthmaticus. The exacerbation was refractory to supplemental oxygen, continuous albuterol, intravenous (IV) steroids, subcutaneous epinephrine, magnesium sulfate and terbutaline infusion. He ultimately required intubation and mechanical ventilation. Isoflurane (1.8% exhaled concentration) was initiated via an anesthesia ventilator. Approximately 12 hours after initiation of isoflurane, the patient was found to have bilateral dilated (5-6 mm) and non-reactive pupils. A non-contrast head CT revealed no acute intracranial pathology. Case Two: A 7 year-old male with past history of asthma presented in severe respiratory distress with hypoxemia. His initial treatment included subcutaneous epinephrine, nebulized albuterol, IV steroids and terbutaline infusion. He eventually required intubation, and was emergently placed on isoflurane (1.8% exhaled concentration) via an anesthesia ventilator. The patient was noted to have bilateral dilated (7-8 mm) and non-reactive pupils within 2 hours of isoflurane initiation. As in case one, a non-contrast head CT revealed no acute intracranial pathology. Discussion: In both cases, the children developed pupillary changes (fixed and dilated pupils) during the initial hours of isoflurane therapy, which resolved within 24 hours of isoflurane discontinuation. The extent to which isoflurane contributed to these findings is unclear. While it is difficult to implicate a single causative agent underlying the pupillary changes observed in both cases, it is likely that isoflurane was a contributing factor. Further investigation is needed to determine the effects of isoflurane administration on pupillary activity.

Does β2-adrenergic stimulation attenuate fluid extravasation during hypothermic cardiopulmonary bypass? An experimental study in pigs

Hypothermic cardiopulmonary bypass (CPB) is associated with increased fluid filtration, edema formation and, occasionally, organ dysfunction. Cold-induced reduction in endothelial barrier function may play a role. β(2)-adrenergic activation elevates cellular cyclic adenosine monophosphate (cAMP) which maintains endothelial barrier properties. In this study, we tested whether β-adrenergic stimulation could influence the increase in fluid extravasation observed during hypothermic CPB. Fourteen pigs randomly received terbutaline infusion (T-group) (n=7) or a control infusion (C-group) (n=7). All animals were given 60 min of normothermic CPB, followed by 90 min of hypothermic CPB. Fluid input and losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum proteins and total tissue water content were measured and the fluid extravasation rates (FER) calculated. by SPSS. Values presented as mean ± SD. Repeated measure analysis of variance was performed and a t-test used when appropriate. The commencement of normothermic CPB resulted in a 20% hemodilution, with an abrupt increase in fluid requirements during the first 10 min. FER increased from 0.18 (0.06) pre-bypass to 0.78 (0.27) ml/kg/min (T-group) (p=0.002) and from 0.16 (0.05) to 0.93 (0.26) ml/kg/min (C-group) (p<0.001) with no between-group differences. Thereafter, FER stabilized at a level of 0.32 (0.13) and 0.27 (0.14) ml/kg/min in the T-group and C-group, respectively. After the start of cooling, FER increased in the T-group to 0.55 (0.12) ml/kg/min (P=0.046) and in the C-group to 0.54 (0.13) ml/kg/min (P=0.006), with no between-group differences (P=0.738). In the present experimental study, we were unable to demonstrate any clinically relevant modulating effect of terbutaline on fluid extravasation during hypothermic cardiopulmonary bypass.

286 The use of continuous infusions of subcutaneous terbutaline in adult patients with cystic fibrosis

286 The use of continuous infusions of subcutaneous terbutaline in adult patients with cystic fibrosis

Effectiveness of terbutaline pump for the prevention of preterm birth. A systematic review and meta-analysis.

BackgroundSubcutaneous terbutaline (SQ terbutaline) infusion by pump is used in pregnant women as a prolonged (beyond 48–72 h) maintenance tocolytic following acute treatment of preterm contractions. The effectiveness and safety of this maintenance tocolysis have not been clearly established. We aimed to systematically evaluate the effectiveness and safety of subcutaneous (SQ) terbutaline infusion by pump for maintenance tocolysis.Methodology/Principal FindingsMEDLINE, EMBASE, CINAHL, the Cochrane Library, the Centre for Reviews and Dissemination databases, post-marketing surveillance data and grey literature were searched up to April 2011 for relevant experimental and observational studies.Two randomized trials, one nonrandomized trial, and 11 observational studies met inclusion criteria. Non-comparative studies were considered only for pump-related harms. We excluded case-reports but sought FDA summaries of post-marketing surveillance data. Non-English records without an English abstract were excluded. Evidence of low strength from observational studies with risk of bias favored SQ terbutaline pump for the outcomes of delivery at <32 and <37 weeks, mean days of pregnancy prolongation, and neonatal death. Observational studies of medium to high risk of bias also demonstrated benefit for other surrogate outcomes, such as birthweight and neonatal intensive care unit (NICU) admission. Several cases of maternal deaths and maternal cardiovascular events have been reported in patients receiving terbutaline tocolysis.Conclusions/SignificanceAlthough evidence suggests that pump therapy may be beneficial as maintenance tocolysis, our confidence in its validity and reproducibility is low, suggesting that its use should be limited to the research setting. Concerns regarding safety of therapy persist.

Serial Cardiac Troponin Concentrations as Marker of Cardiac Toxicity in Children With Status Asthmaticus Treated With Intravenous Terbutaline

The study's objectives were to evaluate serial troponin concentrations as a marker of cardiac toxicity in children receiving intravenous terbutaline for status asthmaticus and to study if troponin concentrations are affected by severity of asthma and risk factors for severe asthma. This was a prospective observational study in 20 consecutive patients who were admitted to a tertiary care pediatric intensive care unit for status asthmaticus and received intravenous terbutaline. Cardiac troponin I (cTnI) concentrations were measured half an hour before the bolus of intravenous terbutaline, 4 hours after terbutaline, and then every 24 hours until discontinuation of the continuous terbutaline infusion. Ten patients had cTnI concentrations greater than 0.03 ng/mL. Maximum cTnI concentrations were recorded after the terbutaline bolus in 6 patients, during terbutaline infusion in 3 patients, and before terbutaline use in 1 patient. Three of these 10 (3/10) patients showed increased cTnI concentrations before the terbutaline bolus. One patient had a significant elevation in cTnI concentration (peak level of 3.79 ng/mL) with electrocardiogram (ECG) changes of myocardial injury that normalized upon discontinuation of terbutaline. All other patients with elevated cTnI concentrations had normal ECG findings. Elevated cTnI concentrations were observed in 50% of patients treated with intravenous terbutaline for status asthmaticus. Clinically significant cardiotoxicity was not observed except in 1 patient in whom the abnormal ECG findings normalized upon discontinuation of terbutaline. There was no statistically significant difference in asthma severity or in the risk factors for severe asthma in children with and without elevation of cTnI concentrations.

Continuous Infusions of Terbutaline in Asthma – A Review

Background. After the safety issues raised by the Salmeterol Multicenter Asthma Research Trial, concerns persist about the safety of agents that cause prolonged β-adrenoceptor stimulation in asthmatic patients. We therefore decided to revisit and review the use of continuous subcutaneous infusions of terbutaline (CSIT)—a treatment often reserved for those with severe and refractory disease. Results. Original studies from the 1980s included 26 patients and showed that CSIT was well tolerated with predominately cutaneous side effects despite maintaining very high serum levels of terbutaline. CSIT led to improved outcomes in approximately 75% of patients which included rises in lowest daily peak expiratory flow rate (PEFR), diminution in diurnal variation, reduction in other medication requirements, and subjective opinion of symptoms. Almost all patients demonstrating an improvement had a wide variation in their pretreatment PEFRs. However, in a retrospective follow-up of 42 patients, the only outcome to be significantly improved by CSIT was that of mean hospital admissions (p = .031). CSIT is theorized to stimulate a discrete set of β-receptors not accessible by the inhaled route as further increases in Forced expiratory volume in one second (FEV1) occur with concurrent nebulized therapy. Conclusion. Although some findings are encouraging, they are drawn from small observational studies done at a time when the standard management of asthma was quite different from today. No randomized controlled trials exist for the use of CSIT, which remains off-license for the treatment of asthma in the United Kingdom. Clearly, prospective well-powered studies are required to fully ascertain its potential benefits and safety profile—something that is unlikely to occur given that the use of CSIT remains low and appears to be declining.

Acute Bronchial Asthma

Acute asthma is the third commonest cause of pediatric emergency visits at PGIMER. Typically, it presents with acute onset respiratory distress and wheeze in a patient with past or family history of similar episodes. The severity of the acute episode of asthma is judged clinically and categorized as mild, moderate and severe. The initial therapy consists of oxygen, inhaled beta-2 agonists (salbutamol or terbutaline), inhaled budesonide (three doses over 1 h, at 20 min interval) in all and ipratropium bromide and systemic steroids (hydrocortisone or methylprednisolone) in acute severe asthma. Other causes of acute onset wheeze and breathing difficulty such as pneumonia, foreign body, cardiac failure etc. should be ruled out with help of chest radiography and appropriate laboratory investigations in first time wheezers and those not responding to 1 h of inhaled therapy. In case of inadequate response or worsening, intravenous infusion of magnesium sulphate, terbutaline or aminophylline may be used. Magnesium sulphate is the safest and most effective alternative among these. Severe cases may need ICU care and rarely, ventilatory support.

Increased cardiac index due to terbutaline treatment aggravates capillary-alveolar macromolecular leakage in oleic acid lung injury in dogs

IntroductionWe assessed the in vivo effects of terbutaline, a beta2-agonist assumed to reduce microvascular permeability in acute lung injury.MethodsWe used a recently developed broncho-alveolar lavage (BAL) technique to repeatedly measure (every 15 min. for 4 hours) the time-course of capillary-alveolar leakage of a macromolecule (fluorescein-labeled dextran) in 19 oleic acid (OA) lung injured dogs. BAL was performed in a closed lung sampling site, using a bronchoscope fitted with an inflatable cuff. Fluorescein-labeled Dextran (FITC-D70) was continuously infused and its concentration measured in plasma and BAL fluid. A two-compartment model (blood and alveoli) was used to calculate KAB, the transport rate coefficient of FITC-D70 from blood to alveoli. KAB was estimated every 15 minutes over 4 hours. Terbutaline intra-venous perfusion was started 90 min. after the onset of the injury and then continuously infused until the end of the experiment.ResultsIn the non-treated injured group, the capillary-alveolar leakage of FITC-D70 reached a peak within 30 minutes after the OA injury. Thereafter the FITC-D70 leakage decreased gradually until the end of the experiment. Terbutaline infusion, started 90 min after injury, interrupted the recovery with an aggravation in FITC-D70 leakage.ConclusionsAs cardiac index increased with terbutaline infusion, we speculate that terbutaline recruits leaky capillaries and increases FITC-D70 leakage after OA injury. These findings suggest that therapies inducing an increase in cardiac output and a decrease in pulmonary vascular resistances have the potential to heighten the early increase in protein transport from plasma to alveoli within the acutely injured lung.

Slow‐responders to IV β2‐adrenergic agonist therapy: Defining a novel phenotype in pediatric asthma

While aerosolized administration of beta(2)-adrenergic receptor (beta(2)-AR) agonists is the mainstay of treatment for pediatric asthma exacerbations, the efficacy of intravenous (IV) delivery is controversial. Failure to demonstrate improved outcomes with IV beta(2)-AR agonists may be due to phenotypic differences within this patient population. Our hypothesis is that children who respond more slowly to IV beta(2)-AR agonist therapy comprise a distinct phenotype. Retrospective chart review of all children admitted to the ICU for status asthmaticus who were treated with IV terbutaline between December 2002 and September 2006. Seventy-eight children were treated with IV terbutaline according to guidelines that adjusted the dose by clinical asthma score. After examining the histogram of duration of terbutaline infusions, a 48-hr cutoff was chosen to define responsiveness. Thirty-eight (49%) children were slow-responders by this definition. There were no significant differences in baseline asthma severity or severity on admission between the slow-responders and responders. Slow-responders required significantly higher total doses of IV terbutaline, higher maximum administration rates, and had longer ICU and hospital length of stay. There were significant differences in outcomes between the responders and slow-responders without differences in acute or chronic illness severity. Other factors may have lead to slower response to IV beta(2)-agonist therapy.

?2-mediated glucose production during carvedilol and metoprolol titration in heart failure

Background Metoprolol and carvedilol are commonly used in heart failure (HF). Previous studies in hypertension indicate worsening of insulin sensitivity with metoprolol but not with carvedilol. However in HF, their relative effects on glucose production have not been directly compared. This study compares fasting glucose and β2-mediated glucose production during metoprolol and carvedilol titration in HF patients. Methods From a previous cohort of HF subjects whose metoprolol or carvedilol were titrated to maximally tolerated doses (up to metoprolol 200mg/d or carvedilol 25mg twice daily) over 5 visits, we analyzed (1) fasting glucose and (2) glucose AUC0–180min upon a β2-agonist (terbutaline) infusion in nondiabetic individuals. Results Fasting glucose (mg/dL) in the metoprolol group (n=9) decreased from 91.1±2.6 (baseline) to 86.9±2.0 (end of titration) while it increased from 91.8±3.1 to 95.7±2.6 with carvedilol (n=6) (p=0.0273, ANCOVA for the comparison between groups). AUC0–180 (mmol/L× 180 min) upon terbutaline infusion decreased from 5.6±0.3 to 4.8±0.1 with metoprolol versus from 5.8±0.3 to 5.0±0.1 with carvedilol (p=NS). AUC0–180 for both metoprolol and carvedilol decreases as drug dosages increase (p=0.0006, repeated measures ANOVA), with a trend toward bigger reduction with metoprolol. Conclusions Metoprolol and carvedilol at clinically relevant doses do not impair fasting glucose in HF. As beta blockade increases, β2-mediated glucose production is reduced. Clinical Pharmacology & Therapeutics (2005) 77, P54–P54; doi: 10.1016/j.clpt.2004.12.096

The occurrence of adverse events in women receiving continuous subcutaneous terbutaline therapy

ObjectiveThe purpose of this study was to determine the frequency of serious adverse events in patients receiving continuous subcutaneous terbutaline after arrested preterm labor. Study designWomen with singleton, twin, and triplet pregnancies prescribed continuous subcutaneous terbutaline were studied. Electronic patient records were reviewed for patient tolerance of medication and serious adverse events. The primary study outcome was the frequency of serious adverse events. ResultsAvailable for analysis were 9359 patient records. Transient medication side effects were reported by 1447 (15.5%) patients. Severe adverse events were identified on 12 patients either during treatment with continuous subcutaneous terbutaline (n=4), or after discontinuation of outpatient treatment (n=8). The most frequent serious adverse event was pulmonary edema (n=9). There was no maternal mortality. ConclusionContinuous subcutaneous terbutaline infusion was associated with an extremely low incidence of serious adverse events. Patients with comorbidities and/or concomitant tocolysis with intravenous magnesium sulfate should be closely assessed for development of serious adverse events.

Modeling the metabolic effects of terbutaline in beta2-adrenergic receptor diplotypes.

Our objective was to determine whether beta(2)-adrenergic receptor polymorphisms influence terbutaline-stimulated changes in glucose, insulin, and potassium concentrations in healthy adults. Seven healthy adults homozygous for the Arg-19/Gly16/Glu27 haplotype (RGE) and seven homozygous for the Cys-19/Arg16/Gln27 haplotype (CRQ) volunteered to receive a 1-hour infusion of terbutaline (0.01 mg/kg). A 2-compartment pharmacokinetic model was fitted to the terbutaline concentrations. Concentrations of glucose and insulin were fitted simultaneously by use of a coupled feedback indirect response model. An indirect response model was also fitted to the plasma potassium concentration versus time data. The -2 log-likelihood ratio test was used to determine whether estimates of the covariates of diplotype and sex improved the model fittings. Demographic variables, anthropometric characteristics, and pharmacokinetics did not differ by diplotype. The coupled feedback model fitted the glucose and insulin concentration data well with excellent precision. Terbutaline stimulated production of glucose (S(1)) to a greater extent in RGE compared with CRQ diplotypes, as follows: S(1) = 0.039 +/- 0.007 (mean +/- SD) versus 0.0276 +/- 0.01, respectively (P <.05, -2 log-likelihood criterion). The baseline values, disposition rate constants for glucose (k(out1)) and insulin (k(out2)), production rate of insulin (S(2)), feedback effect of insulin on glucose (S(3)), and pharmacodynamic parameters for potassium did not differ by diplotype or sex. The beta(2) receptor diplotype influences receptor-stimulated glucose production in healthy, nonobese individuals, which is consistent with beta(2) receptor-mediated hepatic glycogenolysis. Future metabolic studies of this system should consider beta(2) receptor genetic variants.

Is postural tremor size controlled by interstitial potassium concentration in muscle?

Objectives: To determine whether factors associated with postural tremor operate by altering muscle interstitial K+. Methods: An experimental approach was used to investigate the effects of procedures designed to increase...