Long-Acting Β2-Adrenergic Receptor Agonist in Pediatric Asthma

Total Page:16

File Type:pdf, Size:1020Kb

Long-Acting Β2-Adrenergic Receptor Agonist in Pediatric Asthma Allergology International (2004) 53: 69–75 Review Article β Long-acting 2-adrenergic receptor agonist in pediatric asthma Shigemi Yoshihara, Yumi Yamada, Toshio Abe and Osamu Arisaka Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan β ABSTRACT effects, such as 2-adrenergic receptor agonists, have long been used as first-choice agents for asthma attacks. Long-acting β -adrenergic receptor agonists (LABA), 2 In recent years, the pathology of bronchial asthma has a class of agents for the long-term management of come to be recognized as eosinophil-mediated chronic childhood bronchial asthma, are recommended for inflammation of the airways and the clinical value of use in combination with steroid inhalation for the treat- various anti-inflammatory agents, such as inhaled corti- ment of the morning dip in severe childhood asthma. costeroids, has been emphasized,1 even in children. In the present review, salmeterol (SM), a LABA inhalant Therefore, the place of β -adrenergic receptor agonists with a long-acting bronchodilator effect, was com- 2 as therapeutic agents has been reviewed and short- pared with the recently introduced tulobuterol patch acting β -adrenergic receptor agonists (SABA) are pre- (TBP) in terms of safety and efficacy, based on their 2 ferred as relievers, whereas long-acting β -adrenergic respective clinical effects on childhood asthma. From a 2 receptor agonists (LABA) are recommended as controllers clinical perspective, both drugs had a preventive effect (Fig. 1). Salmeterol (SM) is an LABA and the tulobuterol by suppressing the morning dip and exercise-induced patch (TBP), a recently developed β -adrenergic receptor asthma when used concomitantly with an inhaled 2 agonist transdermal absorption system, is a drug delivery corticosteroid, and both agents were associated with a system (DDS) that provides long-acting and effective lower incidence of adverse effects on the cardio- bronchodilation. In the present paper, we review the role vascular system than oral β -adrenergic receptor ago- 2 of these agents as controllers in the treatment of nists. Based on these findings, both SM and TBP are childhood asthma. concluded to be highly efficacious and safe broncho- dilator agents that are appropriate for the long-term management of childhood asthma. β LONG-ACTING 2-ADRENERGIC RECEPTOR AGONISTS Key words: bronchodilator, long-acting β2-adrenergic β receptor agonist, pediatric asthma, salmeterol, short- Of the many formulations of 2-adrenergic receptor actingβ2-adrenergic receptor agonist, tulobuterol agonists available, oral preparations, inhalants, quanti- patch. tative inhalation-type aerosols (aerosol, metered dose inhalers) and patch compounds are currently used. β2- Adrenergic receptor agonists are classified according to INTRODUCTION their β2-adrenergic receptor selectivity, duration of effec- Bronchial asthma is defined as a reversible bronchial tiveness and formulation (Table 1). The SABA have been occlusive disease and agents with potent bronchodilator used to treat acute attacks (relievers) and the oral drugs procaterol, clenbuterol and formoterol have recently been classified as controllers. In recent years LABA, such Correspondence: Dr S Yoshihara, Department of Pediatrics, as salmeterol or TBP, have been shown to have high Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. efficacy in the treatment of severe asthma when com- Email: [email protected] bined with anti-inflammatory agents, such as inhaled Received 27 December 2003. corticosteroids (Fig. 1). 70 S YOSHIHARA ET AL. Fig. 1 Rank of long-acting β2-adrenergic receptor agonists as agents for the treatment of pediatric bronchial asthma. DSCG, disodium cromoglycate; MDI, metered dose inhaler. Table 1 Types and special features of β2-adrenergic receptor agonists Generic name Selectivity Duration of Formulation action (h) (adrenergic receptors) First generation Epinephrine α1, β1, β2 < 1 Injection, inhalant Isoproterenol α1, β1 = β2 < 1 Injection, inhalant Second generation Salbutamol β1 < β2 4–5 Tablet, syrup, dry syrup, inhalant, MDI Terbutaline β1 < β2 4–6 Tablet, syrup, granule Third generation Fenoterol β1 < < β2 8 Tablet, syrup, dry syrup, MDI Procaterol β1 < < β2 8–10 Tablet, minitablet, syrup, inhalant, MDI Tulobuterol β1 < < β2 8 Tablet, dry syrup, patch* Formoterol β1 < < β2 10 Tablet, dry syrup, inhalant Clenbuterol β1 < < β2 10–12 Tablet Salmeterol β1 < < β2 12 Inhalant *Only for Hokunalin®. MDI, metered dose inhaler. Salmeterol Suppressive effect of salmeterol on the morning dip Special features of salmeterol In a randomized double-blind trial of 207 asthmatic β The selectivity of salmeterol for the 2-adrenergic recep- patients ranging in age from 4 to 11 years, changes in tors of airway smooth muscle is approximately 85 000- forced expiratory volume in 1 s (FEV1.0) were compared β fold its selectivity for the 1-adrenergic receptors of the during 12 weeks of treatment with salmeterol (50 µg) β heart, indicating very high 2-adrenergic receptor selec- and a placebo inhalant. The FEV1.0 increased signifi- tivity of the drug.2 Salmeterol manifests efficacy within cantly with improvement in lung function for 12 h on day 15–17 min after inhalation. Although it is slightly slower 1 in the group treated with salmeterol compared with acting than salbutamol, its duration of action is more controls and a similar tendency was observed even after than 12 h, implying that two doses a day are sufficient. the 12 week regimen.3 BRONCHODILATORS IN PEDIATRIC ASTHMA 71 Combined effect of salmeterol and an inhaled > 15%. Exercise loading was performed 1.5 and 9 h corticosteroid in childhood asthma after administration and FEV1.0 was measured 30 min after loading-indicated reductions. The salmeterol inha- The effect of salmeterol combined with an inhaled lant had a prophylactic effect on EIA.11 No differences in corticosteroid was examined in a total of 206 moderate EIA were observed when two salmeterol powder-delivery to severe cases.4 Patients currently being treated with devices were used12 and salmeterol inhalation had a beclomethasone propionate (BDP) or budesonide at a longer-acting prophylactic effect on EIA than the SABA mean dose of 750 µg/day were divided into two groups, albuterol.13 one treated with salmeterol inhalant (50 µg) in combi- nation twice a day for 12 weeks and the other treated without the salmeterol inhalant. The time-related Safety of salmeterol changes (%) in morning peak expiratory flow (PEF) were The safety margin of salmeterol and salbutamol have monitored in the two groups. The results showed marked already been established in a double-blind study on improvement in morning PEF measured at 4 week childhood asthma comparing the two drugs.14 The inci- intervals (during 1–4 weeks, 5–8 weeks and 9–12 weeks) dence of adverse reactions in children in Japan is 2.8% in the combined-treatment group compared with the and one case of palpitations (0.31%) and two cases of monotherapy group, suggesting that the morning dip in tremors (0.62%) have been documented (Table 2). The the former group was markedly suppressed.4 A meta- incidence of adverse effects in the cardiovascular and analysis of the results in patients over 12 years of age nervous systems was significantly lower than with oral showed highly convincing efficacy in patients treated β2-adrenergic receptor agonists. with combination therapy.5,6 Interestingly, methacholine- induced airway hypersensitivity was no more severe in Ranking of salmeterol according to pediatric patients treated with salmeterol alone for 4 months than asthma treatment guidelines in patients treated with salbutamol alone.7 However, controversial findings, such as absence of improvement Salmeterol inhalant is a useful agent with sufficient of airway hypersensitivity in patients treated with salme- efficacy for the long-term management or control of terol alone but improvement in those treated with BDP childhood asthma in ordinary family life. The Global alone, have been reported in patients treated with Initiative for Asthma (GINA) 2002 Guidelines (Fig. 2) salmeterol or BDP alone for 1 year.8 Therefore, the results recommend combined use with an anti-inflammatory cited above do not support treatment with salmeterol agent, such as inhaled corticosteroid, from step 3 1 alone on a long-term basis8,9 and, instead, support onward. In addition, salmeterol has again been recom- therapy with a combination of an LABA and inhaled mended for combined therapy with anti-inflammatory agents, such as inhaled corticosteroids, for 6–15-year- corticosteroid. One reason for this is that β2-adrenergic receptor agonists prevent the decrease in steroid recep- old asthma patients in Japan according to the 2002 tor sensitivity caused by repeated exposure to inhaled Japanese Pediatric Allergy Guidelines on Childhood 15 corticosteroids and, because steroids reverse the down- Asthma Management and Treatment. regulation and reduction in number of β2-adrenergic receptors induced by repeated dosing with β2-adrenergic 10 β receptor agonist, corticosteroids and 2-adrenergic recep- Table 2 Comparison of the adverse effects of salmeterol and tor agonists compensate for the shortcomings of each the tulobuterol patch giving the incidence of adverse effects in other. children after official approval for use in Japan Item TBP Salmeterol Clinical benefits of salmeterol in exercise-induced No. subjects evaluated 401 322 asthma No. with adverse effects 41 9 Incidence adverse
Recommended publications
  • Dosing Time Matters
    bioRxiv preprint doi: https://doi.org/10.1101/570119; this version posted March 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Dosing Time Matters 1 2,3 4,5,6 1* Marc D. Ruben ,​ David F. Smith ,​ Garret A. FitzGerald ,​ and John B. Hogenesch ​ ​ ​ ​ 1 Division​ of Human Genetics, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH, 45229 2 Divisions​ of Pediatric Otolaryngology and Pulmonary and Sleep Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229 3 Department​ of Otolaryngology-Head and Neck Surgery, University of Cincinnati School of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267 4 Department​ of Systems Pharmacology and Translational Therapeutics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 USA 5 Department​ of Medicine, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 USA 6 ​ Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 USA *Corresponding Author. Email: [email protected] Abstract Trainees in medicine are taught to diagnose and administer treatment as needed; time-of-day is rarely considered. Yet accumulating evidence shows that ~half of human genes and physiologic functions follow daily rhythms. Circadian medicine aims to incorporate knowledge of these rhythms to enhance diagnosis and treatment.
    [Show full text]
  • Nystatin Ofloxacin Orciprenaline Sulfate
    JP XV Ultraviolet-visible Reference Spectra 1619 Nystatin A solution prepared as follows: To 10 mg add 50.25 mL of a mixture of diluted methanol (4 in 5) and sodium hydroxide TS (200:1), dissolve by warming at not exceeding 509C,andadddilutedmethanol(4in5)tomake500 mL. Ofloxacin Asolutionin0.1mol/LhydrochloricacidTS(1in150,000) Orciprenaline Sulfate A solution in 0.01 mol/L hydrochloric acid TS (1 in 10,000) 1620 Ultraviolet-visible Reference Spectra JP XV Oxazolam A solution in ethanol (95) (1 in 100,000) Oxethazaine A solution in ethanol (95) (1 in 2500) Oxybuprocaine Hydrochloride An aqueous solution (1 in 100,000) JP XV Ultraviolet-visible Reference Spectra 1621 Oxycodone Hydrochloride Hydrate An aqueous solution (1 in 10,000) Oxymetholone A solution prepared as follows: To 5 mL of a solution in methanol (1 in 5000) add 5 mL of sodium hydroxide-methanol TS and methanol to make 50 mL. Oxytetracycline Hydrochloride Asolutionin0.1mol/LhydrochloricacidTS(1in50,000) 1622 Ultraviolet-visible Reference Spectra JP XV Oxytocin An aqueous solution (1 in 2000) Penbutolol Sulfate A solution in methanol (1 in 10,000) Pentazocine A solution in 0.01 mol/L hydrochloric acid TS (1 in 10,000) JP XV Ultraviolet-visible Reference Spectra 1623 Peplomycin Sulfate Asolutionpreparedasfollows:To4mgadd5mL of copper (II) sulfate TS, and dissolve in water to make 100 mL. Perphenazine 1 Asolutionin0.1mol/LhydrochloricacidTS(1in200,000) Perphenazine 2 A solution obtained by adding 10 mL of water to 10 mL of the solution for Perphenazine 1 1624 Ultraviolet-visible
    [Show full text]
  • Β2 Adrenergic Agonist Suppresses Eosinophil-Induced Epithelial-To- Mesenchymal Transition of Bronchial Epithelial Cells Keigo Kainuma1,2, Tetsu Kobayashi3, Corina N
    Kainuma et al. Respiratory Research (2017) 18:79 DOI 10.1186/s12931-017-0563-4 RESEARCH Open Access β2 adrenergic agonist suppresses eosinophil-induced epithelial-to- mesenchymal transition of bronchial epithelial cells Keigo Kainuma1,2, Tetsu Kobayashi3, Corina N. D’Alessandro-Gabazza2, Masaaki Toda2, Taro Yasuma2, Kota Nishihama2, Hajime Fujimoto3, Yu Kuwabara1,2, Koa Hosoki1,2, Mizuho Nagao1, Takao Fujisawa1 and Esteban C. Gabazza2* Abstract Background: Epithelial-mesenchymal transition is currently recognized as an important mechanism for the increased number of myofibroblasts in cancer and fibrotic diseases. We have already reported that epithelial- mesenchymal transition is involved in airway remodeling induced by eosinophils. Procaterol is a selective and full β2 adrenergic agonist that is used as a rescue of asthmatic attack inhaler form and orally as a controller. In this study, we evaluated whether procaterol can suppress epithelial-mesenchymal transition of airway epithelial cells induced by eosinophils. Methods: Epithelial-mesenchymal transition was assessed using a co-culture system of human bronchial epithelial cells and primary human eosinophils or an eosinophilic leukemia cell line. Results: Procaterol significantly inhibited co-culture associated morphological changes of bronchial epithelial cells, decreased the expression of vimentin, and increased the expression of E-cadherin compared to control. Butoxamine, a specific β2-adrenergic antagonist, significantly blocked changes induced by procaterol. In addition, procaterol inhibited the expression of adhesion molecules induced during the interaction between eosinophils and bronchial epithelial cells, suggesting the involvement of adhesion molecules in the process of epithelial-mesenchymal transition. Forskolin, a cyclic adenosine monophosphate-promoting agent, exhibits similar inhibitory activity of procaterol. Conclusions: Overall, these observations support the beneficial effect of procaterol on airway remodeling frequently associated with chronic obstructive pulmonary diseases.
    [Show full text]
  • Ep 2626065 A1
    (19) TZZ Z_T (11) EP 2 626 065 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 153(4) EPC (43) Date of publication: (51) Int Cl.: A61K 31/137 (2006.01) A61K 31/135 (2006.01) 14.08.2013 Bulletin 2013/33 A61K 31/4704 (2006.01) A61K 31/58 (2006.01) A61K 31/56 (2006.01) A61K 9/12 (2006.01) (2006.01) (2006.01) (21) Application number: 11827927.2 A61K 9/14 A61P 11/06 (86) International application number: Date of filing: 01.02.2011 (22) PCT/CN2011/070883 (87) International publication number: WO 2012/041031 (05.04.2012 Gazette 2012/14) (84) Designated Contracting States: (72) Inventor: WU, Wei-hsiu AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Taipei GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Taiwan (TW) PL PT RO RS SE SI SK SM TR (74) Representative: Patentanwaltskanzlei WILHELM (30) Priority: 28.09.2010 CN 201010502339 & BECK Prinzenstrasse 13 (71) Applicant: Intech Biopharm Ltd. 80639 München (DE) Taipei (TW) (54) COMPOUND COMPOSITION FOR INHALATION USED FOR TREATING ASTHMA (57) An inhaled pharmaceutical composition con- tric way as a controller. The eccentric way control therapy tains primary active ingredients of beta2- agonist and cor- could create a low blood concentration period during the ticosteroids.The pharmaceuticalcompositions disclosed day and minimize the acute tolerance phenomenon (or in the present invention are to be inhaled by a patient so called tachyphylaxis) for bronchodilator - beta2-ago- when needed as a reliever, or administrated in an eccen- nists in treating asthma or other obstructive respiratory disorders.
    [Show full text]
  • Clenbuterol Elisa Kit Instructions Product #101219 & 101216 Forensic Use Only
    Neogen Corporation 944 Nandino Blvd., Lexington KY 40511 USA 800/477-8201 USA/Canada | 859/254-1221 Fax: 859/255-5532 | E-mail: [email protected] | Web: www.neogen.com/Toxicology CLENBUTEROL ELISA KIT INSTRUCTIONS PRODUCT #101219 & 101216 FORENSIC USE ONLY INTENDED USE: For the determination of trace quantities of Clenbuterol and/or other metabolites in human urine, blood, oral fluid. DESCRIPTION Neogen Corporation’s Clenbuterol ELISA (Enzyme-Linked ImmunoSorbent Assay) test kit is a qualitative one-step kit designed for use as a screening device for the detection of drugs and/or their metabolites. The kit was designed for screening purposes and is intended for forensic use only. It is recommended that all suspect samples be confirmed by a quantitative method such as gas chromatography/mass spectrometry (GC/MS). ASSAY PRINCIPLES Neogen Corporation’s test kit operates on the basis of competition between the drug or its metabolite in the sample and the drug- enzyme conjugate for a limited number of antibody binding sites. First, the sample or control is added to the microplate. Next, the diluted drug-enzyme conjugate is added and the mixture is incubated at room temperature. During this incubation, the drug in the sample or the drug-enzyme conjugate binds to antibody immobilized in the microplate wells. After incubation, the plate is washed 3 times to remove any unbound sample or drug-enzyme conjugate. The presence of bound drug-enzyme conjugate is recognized by the addition of K-Blue® Substrate (TMB). After a 30 minute substrate incubation, the reaction is halted with the addition of Red Stop Solution.
    [Show full text]
  • Diamandis Thesis
    !"!#$ CHEMICAL GENETIC INTERROGATION OF NEURAL STEM CELLS: PHENOTYPE AND FUNCTION OF NEUROTRANSMITTER PATHWAYS IN NORMAL AND BRAIN TUMOUR INITIATING NEURAL PRECUSOR CELLS by Phedias Diamandis A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy. Department of Molecular Genetics University of Toronto © Copyright by Phedias Diamandis 2010 Phenotype and Function of Neurotransmitter Pathways in Normal and Brain Tumor Initiating Neural Precursor Cells Phedias Diamandis Doctor of Philosophy Department of Molecular Genetics University of Toronto 2010 &'(!)&*!% The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain brings promise for the treatment of neurological diseases and has yielded new insight into brain cancer. The complete repertoire of signaling pathways that governs these cells however remains largely uncharacterized. This thesis describes how chemical genetic approaches can be used to probe and better define the operational circuitry of the NSC. I describe the development of a small molecule chemical genetic screen of NSCs that uncovered an unappreciated precursor role of a number of neurotransmitter pathways commonly thought to operate primarily in the mature central nervous system (CNS). Given the similarities between stem cells and cancer, I then translated this knowledge to demonstrate that these neurotransmitter regulatory effects are also conserved within cultures of cancer stem cells. I then provide experimental and epidemiologically support for this hypothesis and suggest that neurotransmitter signals may also regulate the expansion of precursor cells that drive tumor growth in the brain. Specifically, I first evaluate the effects of neurochemicals in mouse models of brain tumors. I then outline a retrospective meta-analysis of brain tumor incidence rates in psychiatric patients presumed to be chronically taking neuromodulators similar to those identified in the initial screen.
    [Show full text]
  • Emea/666243/2009
    European Medicines Agency London, 29 October 2009 EMEA/666243/2009 ISSUE NUMBER: 0910 MONTHLY REPORT PHARMACOVIGILANCE WORKING PARTY (PHVWP) OCTOBER 2009 PLENARY MEETING The CHMP Pharmacovigilance Working Party (PhVWP) held its October 2009 plenary meeting on 19-21 October 2009. PhVWP DISCUSSIONS ON SAFETY CONCERNS Below is a summary of the discussions regarding non-centrally authorised medicinal products in accordance with the PhVWP publication policy (see under http://www.emea.europa.eu/htms/human/phv/reports.htm). Positions agreed by the PhVWP for non- centrally authorised products are recommendations to Member States. For safety updates concerning centrally authorised products and products subject to ongoing CHMP procedures, readers are referred to the CHMP Monthly Report (see under http://www.emea.europa.eu/pressoffice/presshome.htm). The PhVWP provides advice on these products to the Committee of Medicinal Products for Human Use (CHMP) upon its request. Antipsychotics - risk of venous thromboembolism (VTE) Identify risk factors for VTE for preventive action before and during treatment with antipsychotics The PhVWP completed their review on the risk of VTE of antipsychotics1. The review was triggered by and based on data from the UK spontaneous adverse drug reactions reporting system and the published literature. The PhVWP carefully considered the data, including the limitations of both information sources, such as the lack of randomised controlled trial data, the heterogeneity of published studies and the potential confounding factors such as sedation and weight gain, commonly present in antipsychotic users. The PhVWP concluded that an association between VTE and antipsychotics cannot be excluded. Distinguishing different risk levels between the various active substances was not possible.
    [Show full text]
  • Lamas for COPD Systematic Review
    Comparative safety and effectiveness of inhaled long -acting agents (corticosteroids, beta agonists, anticholinergics) for chronic obstructive pulmonary disease Comprehensive Research Plan: Systematic Review Unit April 4th, 2014 Andrea C. Tricco, PhD1 and Sharon E. Straus, MD, MSc1,2 30 Bond Street, Toronto ON, M5B 1W8 www.odprn.ca [email protected] Background Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation in the lungs [1]. COPD is commonly assessed by clinical examination and spirometry. Important indicators considered in the diagnosis of COPD include age over 40 years and any of the following: 1) progressive and persistent dyspnea that worsens with exercise, 2) chronic cough, 3) chronic sputum production, 4) history of exposure to smoke from tobacco or cooking, occupational dusts and chemicals, and 5) family history of COPD [1]. COPD causes significant burden of illness, reduced quality of life, and premature death [2]. Symptoms include chronic cough, sputum production, and dyspnea [3]. The global prevalence of COPD has been estimated at 7.6% using data from a systematic review including 28 countries [4]. However, this is likely a conservative estimate, due to under-reporting and under-diagnosis. The prevalence and burden of COPD is rising due the greater proportion of elderly people in the population [1]. It is estimated that COPD will be the third-leading cause of death by 2020 [5]. The treatment of COPD usually involves reducing exposure (e.g., smoking cessation, occupation modifications), increasing exercise, and implementing appropriate pharmacologic therapy [1]. The most common drug classes are beta2-agonists, anticholinergics, and methylxanthines. Inhaled corticosteroids (ICS) and systemic corticosteroids are often useful for acute exacerbations.
    [Show full text]
  • 100 Storage Condition=50 C/Ambrh
    USOO595.5058A United States Patent (19) 11 Patent Number: S.9SS,0589 9 Jager et al. (45) Date of Patent: Sep. 21,9 1999 54). STABILIZED MEDICINAL AEROSOL 56) References Cited SOLUTION FORMULATIONS CONTAINING U.S. PATENT DOCUMENTS IPRATROPIUM BROMIDE a 5,118,494 6/1992 Schultz et al. ............................ 424/45 75 Inventors: Paul Donald Jager, Waterbury; Mark 5,190,029 3/1993 Byron et al. ... ... 128/200.14 James Kontny, New Milford, both of 5,225,183 7/1993 Purewal et al. ........................... 424/45 Conn.; Jurgen Hubert Nagel 5.439,670 8/1995 Purewal et al. ... 424/45 Ingelheim/Rhein, Germany s 5,605,674 2/1997 Purewal et al. ........................... 424/45 FOREIGN PATENT DOCUMENTS 73 Assignee: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, 0372 777 6/1990 European Pat. Off.. Conn. Primary Examiner Raj Bawa Attorney, Agent, or Firm Morgan & Finnegan, LLP 21 Appl.pp No.: 08/843,180 57 ABSTRACT 22 Filed: Apr. 14, 1997 Stabilized medicinal aeroSol Solution formulations compris O O ing medicaments that degrade or decompose by interaction Related U.S. Application Data with solvents or water, an HFC propellant, a cosolvent and an acid are described. Further, Specific medicinal aeroSol 63 Staggypt.NE "A iGs Solution formulations comprising ipratropium bromide or No. 08/153.549, Nov. 22, 1993, abandoned E. is a fenoterol, ethyl alcohol, 1,1,1,2-tetrafluoroethane or 1,1,1, continuation-in-part of application No. 07/987,852, Dec. 9, 2,3,3,3-heptafluoropropane, and either an inorganic acid or 1992, abandoned. an organic acid are described. The acids are present in 51 Int.
    [Show full text]
  • Vr Meds Ex01 3B 0825S Coding Manual Supplement Page 1
    vr_meds_ex01_3b_0825s Coding Manual Supplement MEDNAME OTHER_CODE ATC_CODE SYSTEM THER_GP PHRM_GP CHEM_GP SODIUM FLUORIDE A12CD01 A01AA01 A A01 A01A A01AA SODIUM MONOFLUOROPHOSPHATE A12CD02 A01AA02 A A01 A01A A01AA HYDROGEN PEROXIDE D08AX01 A01AB02 A A01 A01A A01AB HYDROGEN PEROXIDE S02AA06 A01AB02 A A01 A01A A01AB CHLORHEXIDINE B05CA02 A01AB03 A A01 A01A A01AB CHLORHEXIDINE D08AC02 A01AB03 A A01 A01A A01AB CHLORHEXIDINE D09AA12 A01AB03 A A01 A01A A01AB CHLORHEXIDINE R02AA05 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S01AX09 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S02AA09 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S03AA04 A01AB03 A A01 A01A A01AB AMPHOTERICIN B A07AA07 A01AB04 A A01 A01A A01AB AMPHOTERICIN B G01AA03 A01AB04 A A01 A01A A01AB AMPHOTERICIN B J02AA01 A01AB04 A A01 A01A A01AB POLYNOXYLIN D01AE05 A01AB05 A A01 A01A A01AB OXYQUINOLINE D08AH03 A01AB07 A A01 A01A A01AB OXYQUINOLINE G01AC30 A01AB07 A A01 A01A A01AB OXYQUINOLINE R02AA14 A01AB07 A A01 A01A A01AB NEOMYCIN A07AA01 A01AB08 A A01 A01A A01AB NEOMYCIN B05CA09 A01AB08 A A01 A01A A01AB NEOMYCIN D06AX04 A01AB08 A A01 A01A A01AB NEOMYCIN J01GB05 A01AB08 A A01 A01A A01AB NEOMYCIN R02AB01 A01AB08 A A01 A01A A01AB NEOMYCIN S01AA03 A01AB08 A A01 A01A A01AB NEOMYCIN S02AA07 A01AB08 A A01 A01A A01AB NEOMYCIN S03AA01 A01AB08 A A01 A01A A01AB MICONAZOLE A07AC01 A01AB09 A A01 A01A A01AB MICONAZOLE D01AC02 A01AB09 A A01 A01A A01AB MICONAZOLE G01AF04 A01AB09 A A01 A01A A01AB MICONAZOLE J02AB01 A01AB09 A A01 A01A A01AB MICONAZOLE S02AA13 A01AB09 A A01 A01A A01AB NATAMYCIN A07AA03 A01AB10 A A01
    [Show full text]
  • Pharmacology and Therapeutics of Bronchodilators
    1521-0081/12/6403-450–504$25.00 PHARMACOLOGICAL REVIEWS Vol. 64, No. 3 Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics 4580/3762238 Pharmacol Rev 64:450–504, 2012 ASSOCIATE EDITOR: DAVID R. SIBLEY Pharmacology and Therapeutics of Bronchodilators Mario Cazzola, Clive P. Page, Luigino Calzetta, and M. Gabriella Matera Department of Internal Medicine, Unit of Respiratory Clinical Pharmacology, University of Rome ‘Tor Vergata,’ Rome, Italy (M.C., L.C.); Department of Pulmonary Rehabilitation, San Raffaele Pisana Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy (M.C., L.C.); Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King’s College London, London, UK (C.P.P., L.C.); and Department of Experimental Medicine, Unit of Pharmacology, Second University of Naples, Naples, Italy (M.G.M.) Abstract............................................................................... 451 I. Introduction: the physiological rationale for using bronchodilators .......................... 452 II. ␤-Adrenergic receptor agonists .......................................................... 455 A. A history of the development of ␤-adrenergic receptor agonists: from nonselective ␤ Downloaded from adrenergic receptor agonists to 2-adrenergic receptor-selective drugs.................... 455 ␤ B. Short-acting 2-adrenergic receptor agonists........................................... 457 1. Albuterol........................................................................ 457
    [Show full text]
  • Data Reproducibility and Effectiveness of Bronchodilators for Improving Physical Activity in COPD Patients
    Journal of Clinical Medicine Review Data Reproducibility and Effectiveness of Bronchodilators for Improving Physical Activity in COPD Patients Yoshiaki Minakata * and Seigo Sasaki Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital, Wakayama 644-0044, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-738-22-3256 Received: 7 September 2020; Accepted: 27 October 2020; Published: 29 October 2020 Abstract: Increasing physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is an important issue, however, the effect of bronchodilators on PA is still controversial. The indicators of PA, as measured by an accelerometer, can easily fluctuate based on several factors, which might cause inconsistent results. In this review, we listed the indicators of PA and the factors influencing the reproducibility of indicators of PA, and reviewed reports in which the effects of bronchodilators on PA were evaluated by an accelerometer. Then, we investigated the association between the processing of influencing factors and the effectiveness of bronchodilators for improving the PA of COPD patients. Fifteen reports were extracted using the PubMed database. In all seven reports in which adjustment was performed for at least two of four influencing factors (non-wear time, data from days with special behavior, environmental factors, and number of valid days required to obtain reproducible data), bronchodilators showed beneficial effects on PA. No adjustment was made for any of these factors in any of the four bronchodilator-ineffective reports. This suggests that the processing of influencing factors to secure reproducibility might affect the results regarding the effectiveness of bronchodilators for improving PA in COPD patients.
    [Show full text]