Advertisement

Introduction: Methylxanthine therapy and reversible airway obstruction

  • E.R. McFadden Jr.
    Correspondence
    Requests for reprints should be addressed to Dr. E. R. McFadden, Jr., Asthma and Allergic Disease Center, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, Ohio 44106.
    Affiliations
    Asthma and Allergic Disease Center, and the Departments of Medicine of University Hospitals and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Theophylline is a medium-potency bronchodilator that is useful in the treatment of reversible airway obstruction from any cause. It also improves contraction of the diaphragm, accelerates mucociliary transport, lowers pulmonary artery pressures, and limits the release of the mediators of immediate hypersensitivity from mast cells. The pharmacologic effects correlate closely with the plasma concentration of this drug, and within the defined therapeutic limits, only minor adverse effects occur. The dose of theophylline required to achieve therapeutic plasma levels varies considerably between subjects, mainly because of differences in clearance. The latter varies with age, smoking, alterations in hepatic function, cardiac failure, viral infections, and concurrent administration of other drugs. For the treatment of acute symptoms, either intravenous administration or a rapidly absorbed compound such as uncoated tablets or liquids is required. For the long-term management of reversible airway obstruction, sustained-release theophyllines are available. These formulations maintain therapeutic serum theophylline concentrations for prolonged periods, permitting longer dosing intervals and improved patient compliance.

      References

        • Salter H
        On some points in the treatment and clinical history of asthma.
        Edinb Med J. 1858; 4: 1109-1115
        • Herrman G
        • Aynesworth MB
        • Martin J
        Successful treatment of persistent dyspnea of “status asthmaticus”.
        J Lab Clin Med. 1937; 23: 135-148
        • Hendles L
        • Weinberger M
        Theophylline.
        in: A state of the art review. 2nd ed. Pharmacotherapy. 3. 1983: 2-44
        • Andersson KE
        • Persson CG
        Extrapulmonary effects of theophylline.
        Eur J Respir Dis. 1980; 61: 17-28
        • Aubier M
        • Detroyer A
        • Sampson M
        • Macklem PT
        • Roussos C
        Aminqphylline improves diaphragmatic contractility.
        N Engl J Med. 1981; 305: 249-252
        • Murciano D
        • Aubier M
        • Lecocguic Y
        • Pariente R
        Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease.
        N Engl J Med. 1984; 311: 349-353
        • Rees HA
        • MacDonald HR
        • Bothwick RG
        • et al.
        The circulatory effects of aminophylline in man.
        Clin Sci. 1969; 36: 359-369
        • Matthay RA
        • Berger HJ
        • Loke J
        • Gottschalk A
        • Zaret BL
        Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease.
        Am J Med. 1978; 65: 903-910
        • Truitt EB
        • McKusick VA
        • Krantz JC
        Theophylline blood levels after oral, rectal and intravenous administration and correlation with diuretic action.
        J Pharmacol Exp Ther. 1950; 100: 309-315
        • Mitenko PA
        • Ogilvie RI
        Rational intravenous doses of theophylline.
        N Engl J Med. 1973; 289: 600-603
        • Weinberger M
        • Hendeles L
        Experience with theophylline for the management of chronic asthma.
        Eur J Respir Dis. 1980; 61: 120-133
        • Hambelton G
        • Weinberger M
        • Taylor J
        • et al.
        Comparison of cromoglycate (cromolyn) and theophylline in controlling symptoms of chronic asthma.
        Lancet. 1977; I: 381-385
        • Nassif EG
        • Weinberger M
        • Thompson R
        • Huntley W
        The value of maintenance theophylline in steroid-dependent asthma.
        N Engl J Med. 1981; 304: 71-75
        • Bundgaard A
        • Weeke B
        Long-term treatment with oral sustained-release theophylline.
        Allergy. 1982; 37: 149-154
        • Rossing TH
        • Fanta CH
        • Goldstein DH
        • Snapper JR
        • McFadden Jr, ER
        Emergency therapy of asthma: comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline.
        Am Rev Respir Dis. 1980; 122: 365-371
        • Dolson JB
        • Kranowski J
        • Anderson W
        • Sventivany A
        Inhibition of human pulmonary phosphodiesterase activity by therapeutic levels of theophylline.
        Clin Exp Pharmacol Physiol. 1978; 5: 536-539
        • Fredholm B
        Theophylline actions on adenosine receptors.
        Eur J Resp Dis. 1980; 61: 29-35
        • Scott PH
        • Tabachnik E
        • MacLeod S
        • Correia J
        • Newth C
        • Levison H
        Sustained release theophylline for childhood asthma: evidence for circadian variation of theophylline pharmacokinetics.
        J Pediatr. 1981; 99: 476-479
        • Levy G
        • Koysooko R
        Pharmacokinetic analysis of the effect of theophylline on pulmonary function in asthmatic children.
        J Pediatr. 1975; 86: 789-793
        • Stec GP
        • Greenberger P
        • Rou T
        • et al.
        Kinetics of theophylline transfer to breast milk.
        Clin Pharmacol Ther. 1980; 28: 404-408
        • Greening AP
        • Baillie E
        • Gribbin HR
        • Pride NB
        Sustained release oral aminophylline in patients with airflow obstruction.
        Thorax. 1981; 36: 303-307
        • Zwillich CW
        • Sutton FD
        • Neff TA
        • Cohn WM
        • Matthay RA
        • Weinberger M
        Theophylline-induced seizures in adults; correlations with serum concentrations.
        Ann Intern Med. 1975; 82: 784-787
        • Foster LJ
        • Trudran WL
        • Goldman AL
        Bronchodilator effects on gastric acid secretion.
        JAMA. 1979; 241: 2613-2615
        • Jenne JW
        • Wyze E
        • Rood FS
        • MacDonald IM
        Pharmacokinetics of theophylline.
        in: Application to adjustment of the clinical dose of aminophylline. 2nd ed. Clin Pharmacol Ther. 13. 1972: 349-360
        • Ellis EF
        • Jaffe SJ
        • Levy G
        Pharmacokinetics of theophylline in asthmatic children.
        J Allergy Clin Immunol. 1974; 53: 79-84
        • Upton RA
        • Thiercelin J-F
        • Guentert W
        • et al.
        Intraindividual variability in theophylline pharmacokinetics: statistical verification in 39 of 60 healthy young adults.
        J Pharmacokinet Biopharm. 1982; 10: 123-134
        • Dederich RA
        • Szefler SJ
        • Green ER
        Intrasubject variation in sustained-release theophylline absorption.
        J Allergy Clin Immunol. 1981; 67: 465-471
        • Tabachnik E
        • Scott P
        • MacLeod S
        • et al.
        Sustained release theophylline in treatment of childhood asthma—a significant advance.
        J Pediatr. 1982; 100: 489-492
        • Kelly HW
        • Murphy S
        Efficacy of a 12-hour sustained release preparation in maintaining therapeutic serum theophylline levels in asthmatic children.
        Pediatrics. 1980; 66: 97-102
        • Barnes PJ
        • Greening AP
        • Neville L
        • Timmers J
        • Poole GW
        Single-dose slow-release aminophylline at night prevents nocturnal asthma.
        Lancet. 1982; I: 299-301