European Journal of Clinical Pharmacology
Europ. J. clin. Pharmacol. 11, 11-14 (1977)
© by Springer-Verlag 1977
Effect in Bronchial Asthma of a New Beta-Adrenergic Blocking Drug Atenolol (ICI 66, 082) N. P. Boye and J. R. Vale University Department of Lung Diseases, Rikshospitalet, Oslo, Norway
Summary. The bronchial effect of intravenous atenolol (ICI 66.082 ) has been studied in a doubleblind cross over trial in 10 patients with pronounced, labile bronchial asthma. A single i. v. dose of atenolol 3 rag, sufficient to cause a fallin heart rate and systolic blood pressure at rest, induced only a slight and clinically almost negligible impairment of ventilatory function. An ordinary therapeutic dose of salbutamol by inhalation far outweighed the bronchial effect of atenolol. The drug appears promising with regard to its cardio-selective properties. Key words: Atenolol, betal-blockade, bronchial asthma, salbutamol, ventilatory function.
Since the introduction of propranolol several other beta-adrenergic blocking drugs with slightly different pharmacological properties have come into general use. They have a well documented effect in angina pectoris and are also of therapeutic value in arterial hypertension and cardiac arrhythmias [1, 2]. Most of these drugs have a general beta-blocking effect and may induce bronchial constriction if given to patients with bronchial asthma. Practolol differs in this respect by its relative cardioselectivity, as it has an almost negligible blocking effect on the beta 2 receptors of bronchial smooth muscle in therapeutic doses. Unfortunately, serious side-effects have become evident and have led to the withdrawal of practolol from longterm use [3]. Animal studies indicate that a new beta-blocking agent, atenolol (ICI 66, 082), exerts its action on the beta-receptors of the heart in doses that do not affect the bronchial receptors [4]. In this way it resembles practolol, although it also differs from it by the ab-
sence of intrinsic sympathomimetic activity. Clinical trials have demonstrated the therapeutic value of atenolol in hypertension [5, 6] and in angina pectoris [7, 8]. The present study was carried out to determine (i) whether atenolol possessed any clinically important beta2-blocking effect in patients with bronchial asthma, and (if) to discover to what extent any possible atenolol-induced broncho-constriction might be influenced by successive administration of a beta2stimulant.
Patients and Methods
Ten adult in-patients (4 males and 6 females) with a mean age of 47 years (range 28-70) were selected for the study. All had bronchial asthma or asthmatic bronchitis, and their case histories were characterized by lability of broncho-constriction, which had been present for an average of 23 years (range 1-29). At the time of study all were in a relatively stable condition. Details of ventilatory function are listed in Table 1. All except one were on long-term treatment with salbutamol or terbutaline by mouth or by inhalation, three also had oral corticosteroid maintenance therapy, and one patient used beclomethasone diproprionate by inhalation. None showed symptoms or signs of cardiovascular disease on routine-examination, including electrocardiography. All patients gave their consent to participate in the study although informed that the drug under trial would probably be of no direct therapeutic benefit to themselves, and that it might in fact temporarily exacerbate their asthma. The study was designed according to a double blind crossover pattern in randomized sequence. Atenolol 3 mg or placebo (saline) were injected in-
12
N. P. Boye and J. R. Vale: Atenolol in Asthma i ....
Table 1. Basal values of ventilatory parameters in the 10 patients in the trial. All figures, except that of one second forced expiratory volume given as a percentage of vital capacity (FEV %), are expressed in per cent of predicted values for healthy subjects of corresponding sex, age and height [ 10]. For abbreviations, see text
VC FEV 1 FEV% MMFR PEF
91 47 36 20 46
SD
Range
17 15 13 25 15
66-122 30-76 31-61 9-87 26-73
80
°°f
70
min-1
E0
ICI 66082 Placebo
NJi
Europ. J. clin. Pharmacol. 11, 11-14 (1977)
© by Springer-Verlag 1977
Effect in Bronchial Asthma of a New Beta-Adrenergic Blocking Drug Atenolol (ICI 66, 082) N. P. Boye and J. R. Vale University Department of Lung Diseases, Rikshospitalet, Oslo, Norway
Summary. The bronchial effect of intravenous atenolol (ICI 66.082 ) has been studied in a doubleblind cross over trial in 10 patients with pronounced, labile bronchial asthma. A single i. v. dose of atenolol 3 rag, sufficient to cause a fallin heart rate and systolic blood pressure at rest, induced only a slight and clinically almost negligible impairment of ventilatory function. An ordinary therapeutic dose of salbutamol by inhalation far outweighed the bronchial effect of atenolol. The drug appears promising with regard to its cardio-selective properties. Key words: Atenolol, betal-blockade, bronchial asthma, salbutamol, ventilatory function.
Since the introduction of propranolol several other beta-adrenergic blocking drugs with slightly different pharmacological properties have come into general use. They have a well documented effect in angina pectoris and are also of therapeutic value in arterial hypertension and cardiac arrhythmias [1, 2]. Most of these drugs have a general beta-blocking effect and may induce bronchial constriction if given to patients with bronchial asthma. Practolol differs in this respect by its relative cardioselectivity, as it has an almost negligible blocking effect on the beta 2 receptors of bronchial smooth muscle in therapeutic doses. Unfortunately, serious side-effects have become evident and have led to the withdrawal of practolol from longterm use [3]. Animal studies indicate that a new beta-blocking agent, atenolol (ICI 66, 082), exerts its action on the beta-receptors of the heart in doses that do not affect the bronchial receptors [4]. In this way it resembles practolol, although it also differs from it by the ab-
sence of intrinsic sympathomimetic activity. Clinical trials have demonstrated the therapeutic value of atenolol in hypertension [5, 6] and in angina pectoris [7, 8]. The present study was carried out to determine (i) whether atenolol possessed any clinically important beta2-blocking effect in patients with bronchial asthma, and (if) to discover to what extent any possible atenolol-induced broncho-constriction might be influenced by successive administration of a beta2stimulant.
Patients and Methods
Ten adult in-patients (4 males and 6 females) with a mean age of 47 years (range 28-70) were selected for the study. All had bronchial asthma or asthmatic bronchitis, and their case histories were characterized by lability of broncho-constriction, which had been present for an average of 23 years (range 1-29). At the time of study all were in a relatively stable condition. Details of ventilatory function are listed in Table 1. All except one were on long-term treatment with salbutamol or terbutaline by mouth or by inhalation, three also had oral corticosteroid maintenance therapy, and one patient used beclomethasone diproprionate by inhalation. None showed symptoms or signs of cardiovascular disease on routine-examination, including electrocardiography. All patients gave their consent to participate in the study although informed that the drug under trial would probably be of no direct therapeutic benefit to themselves, and that it might in fact temporarily exacerbate their asthma. The study was designed according to a double blind crossover pattern in randomized sequence. Atenolol 3 mg or placebo (saline) were injected in-
12
N. P. Boye and J. R. Vale: Atenolol in Asthma i ....
Table 1. Basal values of ventilatory parameters in the 10 patients in the trial. All figures, except that of one second forced expiratory volume given as a percentage of vital capacity (FEV %), are expressed in per cent of predicted values for healthy subjects of corresponding sex, age and height [ 10]. For abbreviations, see text
VC FEV 1 FEV% MMFR PEF
91 47 36 20 46
SD
Range
17 15 13 25 15
66-122 30-76 31-61 9-87 26-73
80
°°f
70
min-1
E0
ICI 66082 Placebo
NJi
