The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Theodore A Slotkin - One of the best experts on this subject based on the ideXlab platform.
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developmental neurotoxicity resulting from pharmacotherapy of preterm labor modeled in vitro Terbutaline and dexamethasone separately and together
Toxicology, 2018Co-Authors: Theodore A Slotkin, Samantha Skavicus, Frederic J SeidlerAbstract:Abstract Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in increased risk of neurodevelopmental disorders. We used a variety of cell models to establish the critical stages at which neurodifferentiation is vulnerable to these agents and to determine whether combined exposures produce a worsened outcome. Terbutaline selectively promoted the initial emergence of glia from embryonic neural stem cells (NSCs). The target for Terbutaline shifted with developmental stage: at later developmental stages modeled with C6 and PC12 cells, Terbutaline had little effect on glial differentiation (C6 cells) but impaired the differentiation of neuronotypic PC12 cells into neurotransmitter phenotypes. In contrast to the specificity shown by Terbutaline, dexamethasone affected both neuronal and glial differentiation at all stages, impairing the emergence of both cell types in NSCs but with a much greater impairment for glia. At later stages, dexamethasone promoted glial cell differentiation (C6 cells), while shifting neuronal cell differentiation so as to distort the balance of neurotransmitter phenotypes (PC12 cells). Finally, Terbutaline and dexamethasone interacted synergistically at the level of late stage glial cell differentiation, with dexamethasone boosting the ability of Terbutaline to enhance indices of glial cell growth and neurite formation while producing further decrements in glial cell numbers. Our results support the conclusion that Terbutaline and dexamethasone are directly-acting neuroteratogens, and further indicate the potential for their combined use in preterm labor to worsen neurodevelopmental outcomes.
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Terbutaline impairs the development of peripheral noradrenergic projections potential implications for autism spectrum disorders and pharmacotherapy of preterm labor
Neurotoxicology and Teratology, 2013Co-Authors: Theodore A Slotkin, Frederic J SeidlerAbstract:Abstract Terbutaline, a β2-adrenoceptor agonist, is used off-label for long-term management of preterm labor; such use is associated with increased risk of neurodevelopmental disorders, including autism spectrum disorders. We explored the mechanisms underlying Terbutaline's effects on development of peripheral sympathetic projections in developing rats. Terbutaline administration on postnatal days 2–5 led to immediate and persistent deficiencies in cardiac norepinephrine levels, with greater effects in males than in females. The liver showed a lesser effect; we reasoned that the tissue differences could represent participation of retrograde trophic signaling from the postsynaptic site to the developing neuronal projection, since hepatic β2-adrenoceptors decline in the perinatal period. Accordingly, when we gave Terbutaline earlier, on gestational days 17–20, we saw the same deficiencies in hepatic norepinephrine that had been seen in the heart with the later administration paradigm. Administration of isoproterenol, which stimulates both β1- and β2-subtypes, also had trophic effects that differed in direction and critical period from those elicited by Terbutaline; methoxamine, which stimulates α1-adrenoceptors, was without effect. Thus, Terbutaline, operating through trophic interactions with β2-adrenoceptors, impairs development of noradrenergic projections in a manner similar to that previously reported for its effects on the same neurotransmitter systems in the immature cerebellum. Our results point to the likelihood of autonomic dysfunction in individuals exposed prenatally to Terbutaline; in light of the connection between Terbutaline and autism, these results could also contribute to autonomic dysregulation seen in children with this disorder.
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neuroinflammation and behavioral abnormalities after neonatal Terbutaline treatment in rats implications for autism
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: M C Zerrate, Frederic J Seidler, Theodore A Slotkin, Mikhail V Pletnikov, Susan L Connors, D L Vargas, Andrew W Zimmerman, Carlos A PardoAbstract:Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a β2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of Terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given Terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of Terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given Terbutaline on PN 11 to 14. In behavioral tests, animals treated with Terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that β2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.
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Terbutaline is a developmental neurotoxicant effects on neuroproteins and morphology in cerebellum hippocampus and somatosensory cortex
Journal of Pharmacology and Experimental Therapeutics, 2004Co-Authors: Melissa C Rhodes, Frederic J Seidler, Ali Abdelrahman, Charlotte A Tate, Abraham Nyska, Heather L Rincavage, Theodore A SlotkinAbstract:β 2 -Adrenoceptor agonists, especially Terbutaline, are widely used to arrest preterm labor, but they also cross the placenta to stimulate fetal β-adrenoceptors that control neural cell differentiation. We evaluated the effects of Terbutaline administration in neonatal rats, a stage of neurodevelopment corresponding to human fetal development. Terbutaline administered on postnatal days PN2 to 5 elicited neurochemical changes indicative of neuronal injury and reactive gliosis: immediate increases in glial fibrillary acidic protein and subsequent induction of the 68-kDa neurofilament protein. Quantitative morphological evaluations carried out on PN30 indicated structural abnormalities in the cerebellum, hippocampus, and somatosensory cortex. In the cerebellum, PN2 to 5 Terbutaline treatment reduced the number of Purkinje cells and elicited thinning of the granular and molecular layers. The hippocampal CA3 region also displayed thinning, along with marked gliosis, effects that were restricted to females. In the somatosensory cortex, Terbutaline evoked a reduction in the proportion of pyramidal cells and an increase in smaller, nonpyramidal cells; again, females were affected more than males. Although abnormalities were obtained with later Terbutaline treatment (PN11 to 14), in general the effects were smaller than those seen with PN2 to 5 exposure. Our results indicate that Terbutaline is a neurotoxicant that elicits biochemical alterations and structural damage in the immature brain during a critical period. These effects point to a causal relationship between fetal Terbutaline exposure and the higher incidence of cognitive and neuropsychiatric disorders reported for the offspring of women receiving Terbutaline therapy for preterm labor.
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Does Terbutaline damage the developing heart
Birth Defects Research Part B-developmental and Reproductive Toxicology, 2003Co-Authors: Melissa C Rhodes, Frederic J Seidler, Abraham Nyska, Theodore A SlotkinAbstract:BACKGROUND: β2-Adrenoceptor (βAR) agonists, such as Terbutaline, are widely used to arrest preterm labor. They also cross the placenta where they stimulate receptors in fetal tissues, which in turn use βAR input for trophic control of cell replication and differentiation. METHODS: As rats are altricial, we administered Terbutaline in two different postnatal exposure periods (10 mg/kg given daily on Days 2–5 or 11–14). RESULTS: Hearts were examined twenty-four hours after the last dose and on postnatal day 30 for cardiac damage. Neither treatment paradigm caused an increase in cardiac abnormalities compared to controls but quantitative analysis of the number of nuclei indicated reductions in females. CONCLUSIONS: These findings do not support earlier case reports of outright myocardial necrosis after Terbutaline tocolysis in human infants. Nevertheless, the significant statistical association between Terbutaline and cardiac anomalies in epidemiological studies suggest that Terbutaline may sensitize the developing heart to other insults that affect development. Birth Defects Res B 68:449–455, 2003. © 2003 Wiley-Liss, Inc.
Frederic J Seidler - One of the best experts on this subject based on the ideXlab platform.
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developmental neurotoxicity resulting from pharmacotherapy of preterm labor modeled in vitro Terbutaline and dexamethasone separately and together
Toxicology, 2018Co-Authors: Theodore A Slotkin, Samantha Skavicus, Frederic J SeidlerAbstract:Abstract Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in increased risk of neurodevelopmental disorders. We used a variety of cell models to establish the critical stages at which neurodifferentiation is vulnerable to these agents and to determine whether combined exposures produce a worsened outcome. Terbutaline selectively promoted the initial emergence of glia from embryonic neural stem cells (NSCs). The target for Terbutaline shifted with developmental stage: at later developmental stages modeled with C6 and PC12 cells, Terbutaline had little effect on glial differentiation (C6 cells) but impaired the differentiation of neuronotypic PC12 cells into neurotransmitter phenotypes. In contrast to the specificity shown by Terbutaline, dexamethasone affected both neuronal and glial differentiation at all stages, impairing the emergence of both cell types in NSCs but with a much greater impairment for glia. At later stages, dexamethasone promoted glial cell differentiation (C6 cells), while shifting neuronal cell differentiation so as to distort the balance of neurotransmitter phenotypes (PC12 cells). Finally, Terbutaline and dexamethasone interacted synergistically at the level of late stage glial cell differentiation, with dexamethasone boosting the ability of Terbutaline to enhance indices of glial cell growth and neurite formation while producing further decrements in glial cell numbers. Our results support the conclusion that Terbutaline and dexamethasone are directly-acting neuroteratogens, and further indicate the potential for their combined use in preterm labor to worsen neurodevelopmental outcomes.
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Terbutaline impairs the development of peripheral noradrenergic projections potential implications for autism spectrum disorders and pharmacotherapy of preterm labor
Neurotoxicology and Teratology, 2013Co-Authors: Theodore A Slotkin, Frederic J SeidlerAbstract:Abstract Terbutaline, a β2-adrenoceptor agonist, is used off-label for long-term management of preterm labor; such use is associated with increased risk of neurodevelopmental disorders, including autism spectrum disorders. We explored the mechanisms underlying Terbutaline's effects on development of peripheral sympathetic projections in developing rats. Terbutaline administration on postnatal days 2–5 led to immediate and persistent deficiencies in cardiac norepinephrine levels, with greater effects in males than in females. The liver showed a lesser effect; we reasoned that the tissue differences could represent participation of retrograde trophic signaling from the postsynaptic site to the developing neuronal projection, since hepatic β2-adrenoceptors decline in the perinatal period. Accordingly, when we gave Terbutaline earlier, on gestational days 17–20, we saw the same deficiencies in hepatic norepinephrine that had been seen in the heart with the later administration paradigm. Administration of isoproterenol, which stimulates both β1- and β2-subtypes, also had trophic effects that differed in direction and critical period from those elicited by Terbutaline; methoxamine, which stimulates α1-adrenoceptors, was without effect. Thus, Terbutaline, operating through trophic interactions with β2-adrenoceptors, impairs development of noradrenergic projections in a manner similar to that previously reported for its effects on the same neurotransmitter systems in the immature cerebellum. Our results point to the likelihood of autonomic dysfunction in individuals exposed prenatally to Terbutaline; in light of the connection between Terbutaline and autism, these results could also contribute to autonomic dysregulation seen in children with this disorder.
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neuroinflammation and behavioral abnormalities after neonatal Terbutaline treatment in rats implications for autism
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: M C Zerrate, Frederic J Seidler, Theodore A Slotkin, Mikhail V Pletnikov, Susan L Connors, D L Vargas, Andrew W Zimmerman, Carlos A PardoAbstract:Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a β2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of Terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given Terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of Terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given Terbutaline on PN 11 to 14. In behavioral tests, animals treated with Terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that β2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.
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Terbutaline is a developmental neurotoxicant effects on neuroproteins and morphology in cerebellum hippocampus and somatosensory cortex
Journal of Pharmacology and Experimental Therapeutics, 2004Co-Authors: Melissa C Rhodes, Frederic J Seidler, Ali Abdelrahman, Charlotte A Tate, Abraham Nyska, Heather L Rincavage, Theodore A SlotkinAbstract:β 2 -Adrenoceptor agonists, especially Terbutaline, are widely used to arrest preterm labor, but they also cross the placenta to stimulate fetal β-adrenoceptors that control neural cell differentiation. We evaluated the effects of Terbutaline administration in neonatal rats, a stage of neurodevelopment corresponding to human fetal development. Terbutaline administered on postnatal days PN2 to 5 elicited neurochemical changes indicative of neuronal injury and reactive gliosis: immediate increases in glial fibrillary acidic protein and subsequent induction of the 68-kDa neurofilament protein. Quantitative morphological evaluations carried out on PN30 indicated structural abnormalities in the cerebellum, hippocampus, and somatosensory cortex. In the cerebellum, PN2 to 5 Terbutaline treatment reduced the number of Purkinje cells and elicited thinning of the granular and molecular layers. The hippocampal CA3 region also displayed thinning, along with marked gliosis, effects that were restricted to females. In the somatosensory cortex, Terbutaline evoked a reduction in the proportion of pyramidal cells and an increase in smaller, nonpyramidal cells; again, females were affected more than males. Although abnormalities were obtained with later Terbutaline treatment (PN11 to 14), in general the effects were smaller than those seen with PN2 to 5 exposure. Our results indicate that Terbutaline is a neurotoxicant that elicits biochemical alterations and structural damage in the immature brain during a critical period. These effects point to a causal relationship between fetal Terbutaline exposure and the higher incidence of cognitive and neuropsychiatric disorders reported for the offspring of women receiving Terbutaline therapy for preterm labor.
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Does Terbutaline damage the developing heart
Birth Defects Research Part B-developmental and Reproductive Toxicology, 2003Co-Authors: Melissa C Rhodes, Frederic J Seidler, Abraham Nyska, Theodore A SlotkinAbstract:BACKGROUND: β2-Adrenoceptor (βAR) agonists, such as Terbutaline, are widely used to arrest preterm labor. They also cross the placenta where they stimulate receptors in fetal tissues, which in turn use βAR input for trophic control of cell replication and differentiation. METHODS: As rats are altricial, we administered Terbutaline in two different postnatal exposure periods (10 mg/kg given daily on Days 2–5 or 11–14). RESULTS: Hearts were examined twenty-four hours after the last dose and on postnatal day 30 for cardiac damage. Neither treatment paradigm caused an increase in cardiac abnormalities compared to controls but quantitative analysis of the number of nuclei indicated reductions in females. CONCLUSIONS: These findings do not support earlier case reports of outright myocardial necrosis after Terbutaline tocolysis in human infants. Nevertheless, the significant statistical association between Terbutaline and cardiac anomalies in epidemiological studies suggest that Terbutaline may sensitize the developing heart to other insults that affect development. Birth Defects Res B 68:449–455, 2003. © 2003 Wiley-Liss, Inc.
Morten Hostrup - One of the best experts on this subject based on the ideXlab platform.
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influence of exercise in normal and hot ambient conditions on the pharmacokinetics of inhaled Terbutaline in trained men
Scandinavian Journal of Medicine & Science in Sports, 2017Co-Authors: Michael Kreiberg, Sebastian Rzeppa, Peter Hemmersbach, Vibeke Backer, V Becker, Soren Jessen, Morten HostrupAbstract:This study investigated the pharmacokinetics of inhaled Terbutaline at rest and after exercise in normal and hot ambient conditions with respect to doping analysis. Thirteen trained young men participated in the study. Urine and blood samples were collected after inhalation of 4 mg Terbutaline during three trials: exercise in hot ambient conditions (30–35 °C) (EXH), exercise in normal ambient conditions (20–25 °C) (EX), and rest (20–25 °C) (R). Exercise consisted of 130 min at various intensities. Adjustment of urine concentrations of Terbutaline to a specific gravity (USG) of 1.02 g/mL was compared with no adjustment. Area under the serum concentration–time curve within the first 6 h was higher for EX (27 ± 3 ng/mL/h) (P ≤ 0.01) and EXH (25 ± 4 ng/mL/h) (P ≤ 0.05) than for R (20 ± 3 ng/mL/h). When unadjusted for USG, urine concentrations of Terbutaline after 4 h were different in the order EXH > EX > R (P ≤ 0.01). When unadjusted for USG, urine concentrations of Terbutaline were 299 ± 151 ng/mL higher (P ≤ 0.001) after 4 h compared with adjusted concentrations in EXH. Excretion rate of Terbutaline was higher (P ≤ 0.001) for EX than for EXH and R within the first 0–1½ h. In conclusion, EXHs results in higher urine concentrations of Terbutaline. This should be considered when evaluating doping cases of Terbutaline.
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Terbutaline accumulates in blood and urine after daily therapeutic inhalation
Medicine and Science in Sports and Exercise, 2017Co-Authors: Nanna Krogh, Sebastian Rzeppa, Anders Dyreborg, Yvette Dehnes, Peter Hemmersbach, Vibeke Backer, Morten HostrupAbstract:This study investigated pharmacokinetics of Terbutaline after single and seven consecutive days of inhalation in exercising trained men. Twelve healthy young trained men underwent two pharmacokinetic trials comparing single dose (2 mg) and seven consecutive days (2 mg×d-1) of inhaled Terbutaline. After inhalation of Terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of Terbutaline. Samples were analyzed by high performance liquid chromatography–tandem mass spectrometry. Maximum serum concentration of Terbutaline (Cmax) (6.4 (±1.2) vs. 4.9 (±1.2) ng×mL-1, P = 0.01) (mean (±95% confidence interval)) and area under serum concentration-time curve from 0 to 4 hours after inhalation (AUC0-4) (16 (±3) vs. 13 (±2) ng×mL-1×h, P ≤ 0.005) were higher after seven days of inhalation compared to the first day. Seven days of Terbutaline inhalation resulted in accumulation of Terbutaline in urine, in which total urine excretion of Terbutaline was higher after seven days of inhalation compared to the first day (274 ± (43) vs. 194 (±33) μg, P ≤ 0.001). These differences were partly attributed to systemic accumulation of Terbutaline after consecutive days of inhalation, in that baseline serum and urine samples revealed incomplete elimination of Terbutaline. Terbutaline accumulates in serum and urine after consecutive days of inhalation. For doping control purposes, these observations are of relevance if a urine threshold and decision limit is to be introduced for Terbutaline on the World Anti-Doping Agency’s list of prohibited substances, since asthmatic athletes may use their bronchorelievers for consecutive days.
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pharmacokinetics of oral and inhaled Terbutaline after exercise in trained men
Frontiers in Pharmacology, 2016Co-Authors: Anders Dyreborg, Nanna Krogh, Sebastian Rzeppa, Peter Hemmersbach, Vibeke Backer, Morten HostrupAbstract:Abstract Aim The aim of the study was to investigate pharmacokinetics of Terbutaline after oral and inhaled administration in healthy trained male subjects in relation to doping control. Methods Twelve healthy well-trained young men (27 ±2 yrs) (mean ±SE) underwent two pharma-cokinetic trials that compared 10 mg oral Terbutaline with 4 mg inhaled Terbutaline. During each tri-al, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption. Blood (0-4 hours) and urine (0-24 hours) samples were collected before and after administration of Terbutaline. Samples were analyzed for concentrations of Terbutaline by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Results Pharmacokinetics differed between the two routes of administration. Serum Cmax and area under the serum concentration-time curve (AUC) were lower after oral administration compared to inhalation (Cmax: 4.2 ±0.3 vs. 8.5 ±0.6 ng/ml, P≤0.001; AUC: 422 ±23 vs. 1308 ±119 ng/ml×min). Urine concentrations (sum of the free drug and the glucuronide) were lower after oral administration compared to inhalation 2 hours (1100 ±213 vs. 61 ±11 ng/ml, P≤0.05) and 4 hours (734 ±116 vs. 340 ±50 ng/ml, P≤0.001) following administration, whereas concentrations were higher for oral ad-ministration than inhalation 12 hours following administration (190 ±43 vs. 399 ±114 ng/ml, P≤0.05). Urine excretion rate was lower after oral administration than inhalation the first 2 hours following administration (P≤0.001). Systemic bioavailability ratio between the two routes of admin-istration was 3.8:1 (inhaled : oral) (P≤0.001). Conclusion Given the higher systemic bioavailability of inhaled Terbutaline compared to oral, our results indicate that it is difficult to differentiate allowed inhaled use of Terbutaline from prohibited oral ingestion based on urine concentrations in doping control analysis.
Bradley M Peterson - One of the best experts on this subject based on the ideXlab platform.
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continuous intravenous Terbutaline for pediatric status asthmaticus
Critical Care Medicine, 1998Co-Authors: Dimitrios E Stephanopoulos, Roberto Monge, Kenneth H Schell, Pamela Wyckoff, Bradley M PetersonAbstract:Objectives: To determine the clinical effects of intravenous Terbutaline at >0.4 μg/kg/min in children with status asthmaticus; to describe the clinical findings associated with such therapy, including creatinine phosphokinase-myocardial band isoenzyme (CPK-MB) concentrations, electrocardiographic alterations, and decreased diastolic blood pressure (DBP) with Terbutaline usage; and to assess the requirement for epinephrine to counteract the decrease in diastolic blood pressure. Design: A retrospective review of children admitted with status asthmaticus who failed emergency room therapy and required intravenous Terbutaline. Setting: San Diego Children's Hospital Pediatric Intensive Care Unit. Patients: Eighteen children with status asthmaticus, based on clinical and laboratory criteria, between September 1994 and July 1996. Interventions: Epinephrine was added for below-normal decreases in diastolic blood pressure. Measurements and Main Results: Continuous monitoring for arrhythmias, ST-segment changes, and DBP values during variations in the dose of intravenous Terbutaline, with or without epinephrine. CPK-MB concentrations were determined in 15 of 18 patients. Conclusions: Intravenous Terbutaline was well tolerated in asthmatic children for ≤305 continuous hours and at varying doses up to a maximum of 10 μg/kg/min. There was no relationship between the magnitude of CPK-MB concentrations and the Terbutaline or epinephrine doses used. Arrhythmias were rare and not related to either Terbutaline or epinephrine doses. However, ST-segment depression did occur in two patients requiring high-dose epinephrine. Terbutaline significantly lowered DBP when used between 0.4 and 1.0 μg/kg/min, which required epinephrine to be initiated. Epinephrine was not required at Terbutaline doses of >2 μg/kg/min. There was no mortality.
Barry G W Arnason - One of the best experts on this subject based on the ideXlab platform.
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Terbutaline in myasthenia gravis a pilot study
Journal of the Neurological Sciences, 2009Co-Authors: Betty Soliven, Kourosh Rezania, Betul Gundogdu, Barbara Hardingclay, Joel Oger, Barry G W ArnasonAbstract:Abstract The objective of this study was to assess the short-term efficacy and safety of Terbutaline, a β2-adrenergic agonist, in patients with myasthenia gravis (MG) in a randomized, double-blind, placebo-controlled, crossover study. The primary endpoint for efficacy was a reduction of at least 3 points in the quantitative MG score (QMGS). Secondary endpoints included changes in the functional disability scale (FDS), forced vital capacity (FVC), grip strength, anti-acetylcholine receptor (AChR) antibody levels and decremental response. During the Terbutaline phase, five of eight (63%) patients had an improvement in the QMGS of 3.0 or greater, while 3/8 (38%) patients had improvement in the FDS of one grade. No improvement was seen during the placebo period. Statistical analysis using Wilcoxon signed-rank test confirmed that Terbutaline treatment resulted in a significant improvement in QMGS. There was no change in FVC, grip strength or anti-AChR antibody levels, but there was an improvement in the decremental response during Terbutaline phase. Terbutaline was well-tolerated in all study subjects. We conclude that Terbutaline may be an effective adjunct therapy in a subset of patients with myasthenia, although confirmation with larger trials will be required.
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Terbutaline in myasthenia gravis: a pilot study.
Journal of the neurological sciences, 2008Co-Authors: Betty Soliven, Kourosh Rezania, Betul Gundogdu, Joel Oger, Barbara Harding-clay, Barry G W ArnasonAbstract:The objective of this study was to assess the short-term efficacy and safety of Terbutaline, a beta2-adrenergic agonist, in patients with myasthenia gravis (MG) in a randomized, double-blind, placebo-controlled, crossover study. The primary endpoint for efficacy was a reduction of at least 3 points in the quantitative MG score (QMGS). Secondary endpoints included changes in the functional disability scale (FDS), forced vital capacity (FVC), grip strength, anti-acetylcholine receptor (AChR) antibody levels and decremental response. During the Terbutaline phase, five of eight (63%) patients had an improvement in the QMGS of 3.0 or greater, while 3/8 (38%) patients had improvement in the FDS of one grade. No improvement was seen during the placebo period. Statistical analysis using Wilcoxon signed-rank test confirmed that Terbutaline treatment resulted in a significant improvement in QMGS. There was no change in FVC, grip strength or anti-AChR antibody levels, but there was an improvement in the decremental response during Terbutaline phase. Terbutaline was well-tolerated in all study subjects. We conclude that Terbutaline may be an effective adjunct therapy in a subset of patients with myasthenia, although confirmation with larger trials will be required.
