DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20195276

A pharmacoepidemiological study of prescription patterns of β2 sympathomimetic bronchodilators in exacerbation of non-severe asthma in tertiary care hospitals, not needing hospitalization

Moumita Hazra

Abstract


Background: Arformoterol, the (R, R) enantiomer of the racemic (R, R / S, S) diastereomer, formoterol, is a short and long acting β2 agonist bronchodilator. Levosalbutamol, the (R, R) enantiomer of racemic diastereomer (R, R / S, S) salbutamol, has a greater affinity for the β2 receptor. Occupation of β2 receptors by agonists result in the activation of the Gs-adenylyl cyclase-cAMP-PKA pathway, followed by phosphorylative events leading to bronchial smooth muscle relaxation. The aim of this pharmacoepidemiological study was to analyse the prescription patterns, and prescription content analysis, of arformoterol, levosalbutamol, formoterol or salbutamol, in non-severe asthma exacerbation in tertiary care hospitals, not needing hospitalization.

Methods: It was a multi-centre, retrospective, observational and analytical study of 100 asthmatic patients’ hospital medical records, treated with 3 doses of arformoterol, levosalbutamol, formoterol or salbutamol nebulization, followed by peak expiratory flow rates (PEFR) measurement at the baseline and 6 minutes, after each dose; along with adverse effects recording. The number of prescriptions of 100 patients was recorded, the percentage of prescriptions was calculated, and the prescription content analysis was done.

Results: PEFR of the patients showed significant increase after the first, second and third doses of bronchodilator nebulisation, with negligible adverse effects. Salbutamol was most commonly prescribed (45 prescriptions, 45%), followed by levosalbutamol (35 prescriptions, 35%), formoterol (15 prescriptions, 15%) and arformoterol (5 prescriptions, 5%). All aspects of prescription content analysis showed 100% completeness.

Conclusions: Arformoterol was more effective, but equally safe, as compared to levosalbutamol, formoterol and salbutamol. Prescription frequency of salbutamol was followed by levosalbutamol, formoterol and arformoterol. Prescription content analyses showed 100% completeness.


Keywords


Prescription patterns, Arformoterol, Levosalbutamol, Salbutamol, Formoterol, Non-severe asthma

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References


Bousquet J, Mantzouranis E, Cruz AA, Khaled NA, Baena-Cagnani CE, Bleecker ER. Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on severe asthma. J Allergy Clin Immunol. 2010;126(5):926-38.

Barnes PJ. Pulmonary pharmacology. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The pharmacological basis of therapeutics. 12th edn. USA: McGraw Hill 2011: 1031-1065.

Pollart SM, Compton RM, Elward KS. Management of acute asthma exacerbations. Am Fam Physician. 2011;84(1):40-7.

Cazzola M, Segreti A, Matera MG. Novel bronchodilators in asthma. Curr Opin Pulm Med. 2010;16(1):6-12.

Bahadori K, Doyle-Waters MM, Marra C, Lynd L, Alasaly K, Swiston J, et al. Economic burden of asthma: a systematic review. BMC Pulm Med. 2009;9:24.

Hanania NA, Donohue J, Nelson H, Sciarappa K, Goodwin E, Baumgartner R, et al. Long-term safety and efficacy of nebulized arformoterol in subjects with COPD. Chest. 2008;134(4) Suppl 2:106.

Kumar H, Goel A, Chand N, Bhushan B, Chander R, Goel A. To Compare the Clinical Efficacy and Safety of Salbutamol and Levosalbutamol Metered-Dose Inhalers in Patients of Bronchial Asthma. Chest. 2010;138(4):160.

Pauwels RA, Sears MR, Campbell M, Villasantez C, Huang S, Lindh A, et al. Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial. Eur Respir J. 2003;22:787-94.

Blais L, Forget A, Ramachandran S. Relative effectiveness of budesonide/formoterol and fluticasone propionate/salmeterol in a 1-year, population-based, matched cohort study of patients with chronic obstructive pulmonary disease (COPD): Effect on COPD-related exacerbations, emergency department visits and hospitalizations, medication utilization, and treatment adherence. Clin Ther. 2010;32(7):1320-8.

Boonsawat W, Charoenratanakul S, Pothirat C, Sawanyawisuth K, Seearmroongruang T, Bengtsson T, et al. Formoterol (oxis) Turbuhaler as a rescue therapy compared with salbutamol pMDI plus spacer in Patients with acute severe asthma. Respir Med. 2003;97:1067-74.

Bodzenta-Lukaszyk A, Dymek A, McAulay K, Mansikka H. Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study. BMC Pulm Med. 2011;11:28.

Vakily M, Mehvar R, Brocks D. Stereoselective Pharmacokinetics and Pharmacodynamics of Anti-Asthma Agents. 2002;36(4):693-701.

Cho SH, Oh SY, Bahn JW, Choi JY, Chang YS, Kim YK, et al. Association between bronchodilating response to short‐acting β‐agonist and nonsynonymous single‐nucleotide polymorphisms of β ‐adrenoceptor gene. Clin Exp Allergy. 2005;35(9):1162-7.

British Thoracic Society, Scottish Inter Collegiate Guidelines Network. British Guidelines on the Management of Asthma. Thorax. 2008;63(Suppl 4):1-121.

Hanania NA, Sethi S, Koltun A, Ward JK, Spanton J, Ng D. Long-term safety and efficacy of formoterol fumarate inhalation solution in patients with moderate-to-severe COPD. Int J Chron Obstruct Pulmon Dis. 2019;14:117-27.

King P. Role of arformoterol in the management of COPD. Int J Chron Obstruct Pulmon Dis. 2008;3(3):385-92.

Gopinath VP. Rao MS, eds. Management of acute severe asthma. Medicine Update API. 2010;20:784-5.

Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, et al. Global strategy for asthma management and prevention. GINA executive summary. Eur Respir J. 2008;31:143-78.

Das SK, Biswas I, Bandyopadhyay AK, Bairagya TD, Bhattacharya S. A comparative study of efficacy and safety of arformoterol and salbutamol nebulization as rescue therapy in acute non-severe asthma. Indian J Pharmacol. 2011;43(4):463-5.

Arun JJ, Lodha R, Kabra SK. Bronchodilatory effect of inhaled budesonide/formoterol and budesonide/salbutamol in acute asthma: a double-blind, randomized controlled trial. BMC Pediatr. 2012;12:21.

Johnson M. Effects of (beta)2 agonists on resident and infiltrating inflammatory cells. J Allergy Clin Immunol. 2002;110:282-90.

Anderson GP. Formoterol: Pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective (beta) 2 adrenoceptor agonist bronchodilator. Life Sci. 1993;52:2145-60.

Baluk P, McDonald DM. The beta 2 adrenergic receptor agonist formoterol reduces microvascular leakage by inhibiting endothelial gap form formation. Am J Physiol. 1994;266:461-8.

Greiff L, Wollmer P, Andersson M, Syenssona C, Persson CGA. Effects of formoterol on histamine induced plasma exudation in induced sputum from normal subjects. Thorax. 1998;53:1010-13.

Nightingale JA, Rogers DF, Barnes PJ. Differential effect of formoterol on adenosine monophosphate and histamine reactivity in asthma. Am J Respir Crit Care Med. 1999;159:1786-90.

Ketchell RI, Jensen MW, Spina D, O’Connor BJ. Dose-related effects of formoterol on airway responsiveness to adenosine 5′-monophosphate and histamine. Eur Respir J. 2002;19:611-6.

Mirza ZN, Kato M, Kimura H. Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms. Ann Allergy Asthma Immunol. 2002;88:494-500.

Maneechotesuwan K, Essilfie-Quaye S, Meah S, Kelly C, Kharitonov SA, Adcock IM, et al. Formoterol attenuates neutrophilic airway inflammation in asthma. Chest. 2005;128:1936-42.

Jeffery PK, Venge P, Gizycki MJ, Egerod I, Dahl R, Faurschou P. Effects of salmeterol on mucosal inflammation in asthma:a placebo-controlled study. Eur Respir J. 2002;20:1378-85.

Cates CJ, Lasserson TJ. Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events. Cochrane Database Syst Rev. 2010;(1):CD007694.

Bussamra MH, Stelmach R, Rodrigues JC, Cukier A. A randomized, comparative study of formoterol and terbutaline dry powder inhalers in the treatment of mild to moderate asthma exacerbations in the pediatric acute care setting. Ann Allergy Asthma Immunol. 2009;103:248-53.

Aalbers R. Fixed or adjustable maintenance-dose budesonide/formoterol compared with fixed maintenance-dose salmeterol/fluticasone propionate in asthma patients aged >or=16 years:post hoc analysis of a randomized, double-blind/open-label extension, parallel-group study. Clin Drug Investig. 2010;30(7):439-51.

Welsh EJ, Cates CJ. Formoterol versus short-acting beta-agonists as relief medication for adults and children with asthma. Cochrane Database Syst Rev. 2010;(9):CD008418.

Baumgartner RA, Mazzetti A, Claus R. Crossover dose-ranging study of arformoterol in patients with COPD. Proc Am Thorac Soc. 2006: 847.

Hanrahan JP, Hanania NA, Calhoun WJ, Sahn SA, Sciarappa K, Baumgartner RA. Effect of nebulized formoterol on airway function in COPD:results from two randomized trials. COPD. 2008;5:25-34.

Rodrigo GJ, Neffen H, Colodenco FD, Castro-Rodriguez JA. Formoterol for acute asthma in the emergency department:a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2010;104:247-52.