Abstract
The widespread popularity of methylxanthine derivatives should be reassessed in light of current evidence. These drugs are relatively weak bronchodilators, respiratory muscle stimulants and inotropic agents and adverse effects, sometimes life threatening, occur fairly frequently. In contrast, beta-2 adrenergic and anticholinergic bronchodilator aerosols used in asthma or chronic obstructive lung disease, and the prophylactic anti-inflammatory aerosols of corticosteroids and cromolyn provide a spectrum of therapeutic choices which address both the inflammatory and bronchoconstrictor components of acute and chronic airflow limitation. Aerosol bronchodilators, in general, are more potent, are virtually free of important side effects, and do not require costly serum level monitoring. Adrenoceptor agonists, together with inhaled steroids, should be considered first-line drugs of choice in managing patients with reversible airflow obstruction associated with asthma or COPD, while methylxanthines should be relegated to the position of third or fourth line drugs, if they are to be used at all. If they are, they should be used with great caution and close patient supervision and, even then, only if benefit, over and above the aerosol bronchodilators and inhaled anti-inflammatory agents can be demonstrated objectively.
Similar content being viewed by others
References
Littenberg B (1988) Aminophylline treatment in severe, acute asthma: a meta-analysis. JAMA 259:1678–1684
Littenberg B, Gluck EH (1986) A controlled trial of methylprednisolone in the emergency treatment of acute asthma. N Engl J Med 314:150–152
Morgan MDL, Singh BV, Frame MH Williams SJ (1982) Terbutaline aerosol given through pear spacers in acute severe asthma. Br Med J 285:849–850
Ward MJ, MacFarlane JT, Davies D (1982) Treatment of acute severe asthma with intravenous aminophylline and nebulized ipatropium bromide after salbutamol (Abstract). Thorax 37:785
Wolfe JD, Tashkin DP, Calvarese B, Simmons M (1978) Bronchodilator effects of terbutaline and aminophylline alone and in combination in asthmatic patients. N Engl J Med 298:363–367
Joad JP, Ahrens RC, Lindgen SO, Weinberger MM (1987) Relative efficacy of maintenance therapy with theophylline, inhaled albuterol and the combination for chronic asthma. J Allergy Clin Immunol 79:78–85
Shim C, Williams MH Jr. (1980) Bronchial response to oral versus aerosol metaproterenol in asthma. Ann Intern Med 93:428–431
Shim C, Williams MH Jr (1981) Comparison of oral aminophylline and aerosol metaproterenol in asthma. Am J Med 71:452–455
Wald JA, Fernandez E (1987) Gastroesophageal reflux and asthma: pathogenesis, diagnosis and therapy. Semin Respir Med 8:324–331
Rice KL, Leatherman JW, Duane PG, Synder LS, Harmon KR, Abel J, Niewoehner DE (1987) Aminophylline for acute exacerbations of chronic obstructive pulmonary disease—a controlled trial. Ann Intern Med 107:305–309
Hill NS (1988) The use of theophylline in irreversible chronic obstructive pulmonary disease. Arch Intern Med 148:2579–2584
Guyatt GH, Townsend M, Pugsley SO, Keller JL, Short HD, Taylor DW, Newhouse MT (1987) Bronchodilators in chronic air-flow limitation: effects on airway function, exercise capacity, and quality of life. Am Rev Respir Dis 135:1069–1074
Filuk RB, Easton PA, Anthonisen NR (1985) Responses to large doses of salbutamol and theophylline in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1985; 871–874
Eaton ML, Green BA, Church TR, McGowan T, Niewoehner DE (1980) Efficacy of theophylline in “irreversible” airflow obstruction. Ann Intern Med 92:758–61
Eaton ML, MacDonald FM, Church TR, Niewoehner DE (1982) Effects of theophylline on breathlessness and exercise tolerance in patients with chronic airflow obstruction. Chest 82:538–542
Jenne JW, Siever JR, Druz WS, Solano JR, Cohen SM, Sharp JT (1984) The effect of maintenance theophylline therapy on lung work in severe chronic obstructive pulmonary disease while standing and walking. Am Rev Respir Dis 130:600–605
Evans WV (1984) Plasma theophylline concentrations, six minute walking distances, and breathlessness in patients with chronic airflow obstruction. Br Med J 289:1649–1651
Lloberes P, Ramis L, Montserrat JM, Serra J, Campistol J, Picado C, Agusti-Vidal A (1988) Effect of three different bronchodilators during an exacerbation of COPD. Eur Respir J 1:536–539
Murciano D, Aubier M, Lecocquic Y, Pariente R (1984) Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease. N Engl J Med 311:349–353
Matthay RA, Berger HJ, Davies R, Loke J, Gottschalk A, Zaret BL (1982) Improvement in cardiac performance by oral long-acting theophylline in chronic obstructive pulmonary disease. Am Heart J 104:1022–1026
Kongragunta VR, Druz WS, Sharp JT (1988) Dyspnea and diaphragmatic fatigue in patients with chronic obstructive pulmonary disease—responses to theophylline. Am Rev Respir Dis 137:662–667
Wardman AG, Simpson FG, Knox AJ, Page RL, Cooke NJ (1988) The use of high dose inhaled beclomethasone dipropionate as a means of assessing steroid responsiveness in obstructive airways disease. Br J Dis Chest 82:168–171
Sirmans SM, Pieper JA, Lalonde RL, Smith DG, Self GH (1988) Effect of calcium channel blockers on theophylline deposition. Clin Pharmacol Ther 44:29–34
Rog AK, Cuda MP, Levine RA (1988) Induction of theophylline toxicity and inhibition of clearance rates by ranitidine. Am J Med 85:525–527
Furukawa CT, Shapiro CG, Duhamel T, Weimer L, Pierson WE, Bierman CW (1984) Learning and behaviour problems associated with theophylline therapy. Lancet 1:621
Rachelefsky GS, Wo J, Adelson J, Mickey MR, Spector SL, Katz RM, Siegel SC, Rohr AS (1986) Behaviour abnormalities and poor school performance due to oral theophylline use. Pediatrics 78:1133–1138
Bowton DL, Alford PT, McLees BD, Prough DS, Stump DA (1987) The effect of aminophylline on cerebral blood flow in patients with chronic obstructive pulmonary disease. Chest 91:874–877
Suzuki A, Nishimura M, Akiyama Y, Hiraga T, Kikinoski A, Kishi F, Kawakami Y (1989) Aminophylline reduces the brain tissue PO2 in COPD patients. Am Rev Respir Dis 139:A11
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Newhouse, M.T., Lam, A. Management of asthma and chronic airflow limitation: Are methylxanthines obsolete?. Lung 168 (Suppl 1), 634–641 (1990). https://doi.org/10.1007/BF02718188
Issue Date:
DOI: https://doi.org/10.1007/BF02718188