Osmotic release oral drug delivery system of metoprolol in hypertensive asthmatic patients. Pharmacodynamic effects on beta 2-adrenergic receptors. Celiprolol, atenolol and propranolol: a comparison of pulmonary effects in asthmatic patients. The cardioselective and hypotensive effects of bisoprolol in hypertensive asthmatics. Effect of single doses of labetalol, metoprolol, and placebo on ventilatory function in patients with bronchial asthma: interaction with isoproterenol. Comparison of respiratory effects of two cardioselective beta-blockers, celiprolol and atenolol, in asthmatics with mild to moderate hypertension. A comparative study on the ventilatory and haemodynamic effects of xamoterol and atenolol in asthmatic patients. Effects of exercise on practolol-treated asthmatic patients. Cardioselectivity of atenolol in asthmatic patients. Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation. Ventilatory effects of ordinary and slow-release tablets of metoprolol in asthmatic patients. Effect of beta-adrenergic blockade on hyperventilation and exercise tolerance in emphysema. Labetalol, beta blockers, and acute deterioration of chronic airway obstruction. Ventilatory effects of beta 1-receptor-selective blockade with bisoprolol and metoprolol in asthmatic patients. Comparative effects of celiprolol, propranolol, oxprenolol, and atenolol on respiratory function in hypertensive patients with chronic obstructive lung disease. A comparison of four beta-adrenoceptor antagonists in patients with asthma. Effects of terbutaline and atenolol on large and small airways in asthmatic patients. -Adrenergic blockade with practolol in acetylcholine-sensitive asthma patients. Asthma and beta-blockers. Cardioselectivity of atenolol and metoprolol. A study in asthmatic patients. Ventilatory effects of atenolol and bevantolol in asthma. Effects of intravenous propranolol and metoprolol and their interaction with isoprenaline on pulmonary function, heart rate and blood pressure in asthmatics. A comparison of celiprolol and chlorthalidone in hypertensive patients with reversible bronchial obstruction. Effects of high doses of celiprolol in asthmatic patients. The effects of dilevalol, metoprolol, and placebo on ventilatory function in asthmatics. Comparative evaluation of cardioselectivity of metoprolol OROS and atenolol: a double-blind, placebo-controlled crossover study. Effect of metoprolol on cardiac and pulmonary function in chronic obstructive pulmonary disease. Ventilatory and haemodynamic effects of beta 1-selective and beta 2-selective stimulation in asthmatic patients. Comparison of the effects of acebutolol (Sectral) and practolol (Eraldin) on airways obstruction in asthmatics.
This study investigated the effects of an osmotic release oral drug delivery system of metoprolol on the changes induced by cumulative doses of inhaled salbutamol on bronchomotor tone, skeletal muscle, and the circulatory system after single (day 1) and multiple (day 7) dosing in 18 hypertensive asthmatic patients (forced expiratory volume in 1 second > 50% predicted; diastolic blood pressure > 90 mm Hg). The patients were given 14/190 mg metoprolol, 100 mg atenolol, and placebo once daily for a 7-day period each in a randomized, double-blind, crossover design. At the estimated time of peak plasma concentrations, cumulative doses of salbutamol (12.5, 37.5, 112.5, 412.5, 812.5, and 1612.5 micrograms) were applied every 20 minutes. Specific airway conductance, finger tremor amplitude, heart rate, and blood pressure were registered at baseline and at each dose increment. The slopes of the salbutamol dose-response curves of specific airway conductance did not differ on day 1 (P > .05). On day 7, atenolol caused a shift of the dose-response curves of specific airway conductance to the right (P < .05), whereas metoprolol was indistinguishable from placebo (P > .05). The median cumulative salbutamol concentrations causing a 50% increase in specific airway conductance were 416 and 384 micrograms (days 1 and 7, respectively) for placebo, 594 and 444 micrograms for metoprolol, and 562 and 1419 micrograms for atenolol. The median cumulative salbutamol concentrations causing a 35% increase in tremor were 732 and 706 micrograms for placebo, 812 and 1213 micrograms for metoprolol, and 797 and 1323 micrograms for atenolol.(ABSTRACT TRUNCATED AT 250 WORDS) Celiprolol, a new beta-adrenoceptor antagonist, blocks serotonin- and methacholine-mediated bronchoconstriction in animals, even in the presence of propranolol. In two, randomized, placebo-controlled, 5-way crossover trials, the pulmonary effects of celiprolol 200 and 400 mg, propranolol 40 mg and atenolol 100 mg were compared in 34 asthmatic patients. Pulmonary function was measured after single doses of each agent, and again following subsequent, graded doses of albuterol or isoproterenol aerosol. Changes in one-second forced expiratory volume (FEV1) and maximal midexpiratory flow rate (FEF25-75) prior to albuterol or isoproterenol were positive after placebo and both doses of celiprolol. Propranolol, and to a lesser extent, atenolol, caused significant reductions in both measures of pulmonary function. Overall changes in FEV1 following each drug plus isoproterenol or albuterol were positive, in the rank order, celiprolol approximately placebo greater than atenolol greater than propranolol. Propranolol pretreatment caused a significant reduction in the effect of bronchodilator. Unlike atenolol and propranolol, celiprolol was highly bronchosparing and did not antagonize sympathomimetic bronchodilators. The cardioselectivity and hypotensive properties of the beta 1-specific beta-blocker bisoprolol were investigated using a single-dose comparison of 10 and 20 mg bisoprolol, 100 mg atenolol, and placebo in 12 hypertensive asthmatic patients. The study was of a randomised four-way crossover design with 1 week's washout between each treatment. beta 1-Selectivity was determined by using lung function parameters--vital capacity (VC), airway resistance (AWR), peak expiratory flow rate (PEFR), forced expiratory volume (FEV1)--at baseline and at predetermined intervals following each medication and salbutamol challenge. Potency of beta-blockade was determined using heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP). 100 mg atenolol and 10 and 20 mg bisoprolol reduced HR, SBP, and DBP 2 h postmedication. All active treatments produced only small nonsignificant reductions in PEFR, FEV1, and VC, compared with baseline, without any significant differences between the four groups. Bisoprolol at both dose levels had only a minor nonsignificant influence on AWR. 100 mg atenolol significantly increased AWR, compared with placebo. Following all treatments, salbutamol did not affect cardiovascular parameters, but significantly reduced AWR and increased PEFR, FEV1, and VC without any significant differences between groups. Bisoprolol, at both dose levels tested, was found to possess a strong beta 1-adrenoceptor-blocking activity without affecting bronchial beta 2-adrenoceptors. An equipotent beta 1-adrenoceptor-blocking dose of atenolol (100 mg), compared with 10 and 20 mg bisoprolol, was found to increase airway resistance in the population of asthmatic patients studied. Bisoprolol has been shown to exhibit a greater beta 1-selectivity than atenolol. The effects of labetalol, metoprolol, and placebo on pulmonary function and their interaction with isoproterenol were evaluated in 18 patients with reversible bronchial asthma [isoproterenol-induced increase in forced expiratory volume in 1 second (FEV1) of greater than or equal to 15%]. Two dose levels of each medication were studied (on consecutive days), with the lower doses of these drugs given randomly. When the lowest values during the 2-hour postdrug evaluation period were considered, FEV1 significantly increased (10.9%; 15.4%) following labetalol (200 and 400 mg, respectively), significantly decreased (-11.2%; -5.4%) after metoprolol (100 and 200 mg, respectively), and was unchanged after placebo. The effects of the three treatments on forced vital capacity (FVC) and maximal midexpiratory flow (MMEF) were qualitatively similar to those observed in FEV1. When isoproterenol was administered following labetalol (200 and 400 mg), FEV1 further increased with a resulting combined increase of 18.9 and 19.7%, respectively, indicating an additive interaction. The effect of isoproterenol was blunted by metoprolol (100 and 200 mg) (p less than 0.01, difference from the effect observed after labetalol and isoproterenol), indicating antagonistic interaction between these two drugs. Labetalol may be a safer antihypertensive than metoprolol in patients with concomitant bronchial asthma. The effects of two cardioselective beta-adrenergic blocking agents--celiprolol (claimed to have bronchodilator properties) and atenolol (without such claims)--on respiratory function and control of asthma were studied in ten asthmatic patients with mild to moderate essential hypertension. Following a beta-2 agonist-free period of ten hours, administration of 100 mg of atenolol was associated with bronchoconstriction (p less than 0.05), whereas 400 mg of celiprolol was not. Responsiveness to beta-2 agonist therapy was retained with both agents (p less than 0.05). Day-to-day asthma control, interpreted from patient recordings of peak flow, inhaler use and symptom scores, were all no different on either agent from placebo. When given acutely, celiprolol appeared to have acute bronchosparing properties, possibly providing a greater margin of respiratory safety than atenolol. The effects of single oral doses of atenolol 50 mg and xamoterol 200 mg (a recently developed partial beta 1-adrenoceptor agonist) on lung function, heart rate and blood pressure were investigated in 11 patients with asthma. Xamoterol caused a significant increase in heart rate and systolic blood pressure, which changes are consistent with the partial beta 1-adrenoceptor agonist activity of this drug. Atenolol induced a significant decrease in FEV1 and the forced vital capacity (FVC); there was a non-significant change in FEV1 and FVC after xamoterol. There was no significant difference between the effects of atenolol and xamoterol of FEV1 and FVC. Bronchospasm induced by atenolol 50 mg and xamoterol 200 mg was completely reversed by inhalation of the beta 2-adrenoceptor agonist terbutaline to a cumulative dose of 4.0 mg. nan This double-blind, randomised, within patient, placebo-controlled study set out to investigate the effect of a cardioselective beta-blocker, atenolol, at different oral doses (50, 100 and 200 mg) and a non-selective agent, propranolol (40 mg), upon 1. airways resistance (forced expiratory volume at one second = FEV1) and 2. the bronchodilator action of increasing doses of inhaled isoprenaline, in patients with co-existent hypertension and reversible airways obstruction. In 10 patients, two hours after drug administration, the 3 doses of atenolol caused a significantly greater (P less than 0.05) degree of B1-blockade than propranolol. In contrast the 3 doses of atenolol caused significantly less (P less than 0.05 to 0.01) B2-blockade as evidenced by a smaller fall in FEV1. The isoprenaline FEV1 dose response curves were displaced progressively to the right of the placebo curve with increasing doses of atenolol, but the greatest displacement was with propranolol. It was concluded that patients with reversible airways obstruction who require beta-blockade should be given a low dose of a cardioselective agent in conjunction with, if required, a beta 2 stimulant such as isoprenaline. Such a treatment will be less likely to cause a troublesome increase in airways resistance and the bronchodilator action of the beta 2 stimulant will be almost fully preserved. In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV1) were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p less than 0.01). Changes in FEV1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p less than 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV1. Moreover, in the context of this study, since the beta-blockers were given in doses likely to induce equivalent cardiac beta-blockade, there is no evidence to suggest that any one of them is more "cardioselective" than the others. The effect of the beta 1-selective adrenoceptor blocker, metoprolol, on ventilatory function was studied in eight asthmatic patients in relation to the plasma level of the agent following its administration in ordinary and slow-release tablets. Metoprolol causes a slight decrease in ventilatory function as compared with placebo. The effect was most pronounced after administration of 200 mg in ordinary tablets, which induced the highest plasma levels. After administration of 200 mg in slow-release tablets the plasma levels were lower and the ventilatory effect was less marked. The bronchial obstruction largely improved after administration of the beta 2-receptor stimulating agent terbutaline. This study indicates, that when a larger dose of metoprolol is used in patients with obstructive lung disease, slow-release durules are to be preferred to ordinary tablets. Ventilation, heart rate, and arterial blood gas tensions were measured at rest and during incremental exercise in 10 patients with emphysema after intravenous placebo or 7 mg metoprolol. Metoprolol reduced heart rate by 14% (P less than 0.001) and ventilation by 11% (P less than 0.01), but there was no significant difference in arterial O2 or CO2 tension (Pao2 and PaCO2, respectively). Metoprolol increased the time to exhaustion on a cycle ergometer (P less than 0.05) but did not improve the 12-min walking distance. A double-blind randomized crossover comparison of 4 wk treatment with atenolol (100 mg/day), metoprolol (100 mg/day), or matched placebo was performed in 12 patients with emphysema. Both beta-adrenoceptor antagonists reduced resting heart rate by 33% (P less than 0.001) and resting minute ventilation by 11% (P less than 0.025). There was no change in resting or exercise Pao2 or Paco2. During steady-state exercise on a cycle ergometer, atenolol and metoprolol reduced ventilation by 14 and 4%, respectively. This was accompanied by 11 and 5% reductions in O2 consumption (P less than 0.05) and 13 and 6% falls in CO2 production (P less than 0.05). There were no significant changes in tests of exercise tolerance, but forced expiratory volume in 1 s and forced vital capacity were reduced during beta 1-adrenergic blockade. beta 1-Blocking drugs reduce hyperventilation in emphysema by reducing pulmonary gas exchange without a change in arterial blood gas tensions. Increased airflow obstruction prevents this reduction being of therapeutic value. The effects on lung function of labetalol (a combined alpha and beta adrenergic receptor blocker) and three beta adrenergic receptor blockers (propranolol, atenolol, metoprolol) have been assessed in patients with chronic airflow obstruction using a double-blind trial. With the dosages used, all drugs produced an equivalent fall of blood pressure. Propranolol was the only drug that significantly increased airways obstruction (FEV1, specific airways resistance). Following salbutamol, labetalol was associated with a significantly greater improvement of airflow than either propranolol or metoprolol. On these acute studies, the order of preference for beta blocking drugs in management of hypertension in patients with obstructive airways disease, would be labetalol, (atenolol) or (metoprolol) and then propranolol. In a double blind, placebo-controlled study the ventilatory effects of the beta 1-selective receptor blockers bisoprolol (EMD 33512) and metoprolol and their interactions with the beta 2-adrenoceptor agonist terbutaline were investigated in 8 asthmatic patients. Both beta-blockers, in all the doses given, caused a significant decrease in peak expiratory flow rate (PEFR). Vital capacity (VC) and forced expiratory volume in one second (FEV1) were significantly decreased only after 10 mg bisoprolol. Terbutaline inhalation caused the same significant improvements in FEV1 and PEFR during placebo as during bisoprolol 10 mg, bisoprolol 20 mg and metoprolol 100 mg. Both beta-blockers caused equal changes in heart rate (HR) at rest. Systolic and diastolic blood pressure (BP) decreased significantly after bisoprolol 20 mg and metoprolol 100 mg, but not after bisoprolol 10 mg. Inhalation of terbutaline up to a dose of 3.5 mg had no influence on HR and BP. The results point to good beta 1-selectivity of bisoprolol 10 mg and 20 mg and metoprolol 100 mg in asthmatic patients. No correlation was found between the plasma levels of the beta-blockers and the changes in the ventilatory indices, HR or BP. The aim of the study was to compare the pulmonary effects of four beta-blockers with different ancillary properties: propranolol (non-beta 1 selective without ISA), oxprenolol (non-beta 1 selective with ISA), atenolol (beta 1 selective), and celipropol (beta 1 selective with mild beta 2-agonist and alpha 2-antagonist activity) in hypertensive patients with chronic obstructive lung disease. Ten asthmatic patients, all males, aged 50-66 years were studied. Entry criteria were a) DBP greater than or equal to 95 mmHg and less than or equal to 115 mmHg; b) FEV1 less than 70% of the theoretical values; c) FEV1 increase of at least 20% after salbutamol inhalation (200 micrograms). After a 2-week washout period on placebo, each patient received propranolol (80 mg/day), oxprenolol (80 mg/day), atenolol (100 mg/day), and celiprolol (200 mg/day) for 1 week, according to a randomized, cross-over design. At the end of the washout and of each treatment period, airway function, assessed by FEV1, FVC, and FEV1%, was evaluated by spirometry both in the basal condition and after salbutamol inhalation. Unlike propranolol and oxprenolol, which significantly reduced FEV1 and inhibited the bronchodilator response to inhaled salbutamol, atenolol and celiprolol did not significantly affect respiratory function and did not antagonize salbutamol effects. Celiprolol more closely approached placebo in its respiratory effects than did atenolol, although the differences were not statistically significant. 1 Cardiovascular and airways response to two non-cardioselective beta-adrenoceptor blocking drugs, propranolol and pindolol (with partial agonist activity) and two cardioselective beta-adrenoceptor blocking drugs, acebutolol (with partial agonist activity) and atenolol, were compared in twelve patients with asthma. 2 All four drugs produced a significant reduction in resting pulse rate and prevented the increase in heart rate following inhaled isoprenaline (1,500 microgram). 3 Seven patients in clinical remission showed no significant bronchoconstrictor response to any of the drugs. In the remaining five patients, bronchoconstriction was greatest following propranolol (mean reduction in FEV1 26.6%) and least following atenolol (mean reduction in FEV1 6.5%). 4 The bronchodilator response to inhaled isoprenaline was blocked by propranolol and pindolol but not by acebutolol and atenolol. 5 Partial agonist activity did not appear to be clinically useful. In order to localize the main site of action of the beta 2-adrenoceptor selective agonist terbutaline and the beta 1-adrenoceptor selective antagonist atenolol in the airways of asthmatic patients, we compared the effects of these drugs on maximal expiratory flow-volume (MEFV) curves when breathing air and when breathing a helium-oxygen (HeO2) mixture. To investigate whether a shift in localization of the bronchodilator effect occurs when terbutaline is inhaled repeatedly, dose-response curves with terbutaline were performed for parameters derived from MEFV curves when breathing air and for density dependence of expiratory airflow. By measurement of MEFV curves when the patients were breathing air alone, it was not possible to determine whether there is a difference in the bronchoconstrictor effect of atenolol between large and small airways. Inhalation of terbutaline to a cumulative dose of 2.0 mg induced a stepwise improvement in expiratory airflow parameters for large and small airways function when breathing air. Doubling the dose of inhaled terbutaline to 4 mg did not result in any further improvement of lung function. Neither atenolol nor terbutaline induced significant mean changes in density dependence of expiratory airflow. This was partly due to large inter- and intra-individual variations of this parameter. Another possibility is that atenolol and terbutaline effect large and small airways function equally. nan In a randomized, blind crossover study in 14 hypertensive patients with asthma, involving placebo and chronically administered (3 weeks) equipotent beta1-blocking doses of atenolol 100 mg once daily and metoprolol 100 mg bid, atenolol and metoprolol produced a similar fall in blood pressure. Atenolol caused significantly (p less than 0.05) less bronchospasm in terms of fewer asthmatic attacks, more asthma-free days, less frequent sensations of moderate to very severe, wheeziness and less effect on the evening peak flow rate. It was concluded that, in patients with asthma who require beta blockade, atenolol is the preferred agent, co-prescribed with a beta2 stimulant. Eight asthmatic patients were investigated in a double-blind cross-over study after oral administration of 100 mg atenolol, 10 mg metoprolol and placebo. Four increasing doses of terbutaline (0.036-1.23 micrograms kg-1 min-1) were thereafter administered by intravenous infusion, starting 120 min after the tablet intake. The infusions were given for 6 min on each dose level with 30-min intervals. The study was finished by inhalation of six terbutaline puffs (1.5 mg). Both atenolol and metoprolol lowered resting heart rate and FEV1 significantly and produced a down- and rightward shift of the dose-response curves to infused terbutaline. No differences between effects of the two beta-blockers were shown in reduction of heart rate and FEV1, before and during the terbutaline treatments. Differences in cardioselectivity between atenolol and metoprolol could thus not be shown. The cardioequipotency of 400 mg bevantolol and 100 mg atenolol was determined by measuring the exercise heart rate in healthy subjects. The beta-blockers were then used in these doses to investigate their ventilatory effects in patients with asthma. The effects of both drugs on forced expiratory flow parameters for large and small airways were assessed at rest and during and after exercise. A dose-response curve was then plotted after inhalation of the beta 2-adrenoceptor agonist terbutaline. Bevantolol significantly decreased the forced expiratory volume in 1 second (FEV1) and the peak expiratory flow rate (PEFR) at rest, while there was no such change with placebo or atenolol. Both beta-blockers decreased the maximal expiratory flow rates at 50% of forced vital capacity (MEF50) and after expiration of 75% of the forced vital capacity (MEF25) at rest; the decrease was larger after bevantolol than after atenolol. During atenolol there was a decrease in FEV1 and in PEFR (P less than 0.01) 15 minutes after exercise in comparison with preexercise values. There was no significant difference between pre- and postexercise values of MEF50 and MEF25 during atenolol dosing. After bevantolol there was only a small change in PEFR after exercise, probably because of the low preexercise values of the ventilatory indices with this drug. Inhalation of terbutaline up to a dose of 2 mg significantly improved all ventilatory indices measured, but with bevantolol the values after 2 mg inhaled terbutaline were lower than the initial values.(ABSTRACT TRUNCATED AT 250 WORDS) The effects of propranolol (0.06 mg/kg i.v.), the selective beta1-receptor antagonist metoprolol (0.12 mg/kg i.v.) and a placebo on pulmonary function, heart rate and blood pressure have been compared in asthmatics. The interaction of these drugs with increasing doses of isoprenaline on the same variables was also studied. The two beta-blockers reduced resting heart rate to the same extent, indicating the same degree of blockade of cardiac beta-receptors. Both beta-blockers reduced the basal forced expiratory volume in one second (FEV1), and the effect tended to be more pronounced after propranolol. Isoprenaline caused a dose-dependent increase in FEV1 and vital capacity (VC). These effects were almost completely blocked by propranolol, whereas after metoprolol the changes approached that of the placebo. The isoprenaline-induced increase in heart rate and fall in diastolic blood pressure was also inhibited to a considerably greater extent by propranolol than by metoprolol. The results show a selectivity of metoprolol for so-called beta1-receptors and indicate that metoprolol may be used in asthmatics provided that it is combined with beta2-receptor-stimulating drugs. The objective of this study was to evaluate the effects of celiprolol, a new beta-blocking drug, on the clinical condition and pulmonary function of hypertensive patients with reversible bronchial obstruction. Celiprolol was compared with chlorthalidone, an antihypertensive drug without known effect on bronchial tone. The study consisted of a 4-week placebo run-in period and a 12-week titration period in which the dose of both drugs was increased at 4-week intervals if blood pressure was not reduced adequately. The doses of celiprolol were 200, 400, or 600 mg once daily; those for chlorthalidone 12.5, 25, or 37.5 mg once daily. Entry criteria were a diastolic blood pressure between 90 and 115 mg Hg, and FEV-1 between 40% and 80% of predicted value, increasing by 15% or more after salbutamol, and a need for occasional bronchodilator therapy. Prophylactic medication for asthma was given in constant dosage for a month before the study and throughout the study. Preliminary results on 66 patients demonstrate that neither drug had a clinically significant effect on FEV-1, FEF 25-75, or FVC. Clinical variables were not significantly changed by either drug: the average monthly asthma attacks fell from 18 to 13 with celiprolol and from 11 to 7 with chlorthalidone. FEF was reduced by more than 50% in two patients on celiprolol and three on chlorthalidone. Monthly asthma attacks increased by more than 100% in five patients on celiprolol and four on chlorthalidone. Thus, preliminary results are unable to demonstrate adverse effects from celiprolol in patients with asthma and hypertension. Sixteen normotensive asthmatic patients received single doses of 400 and 600 mg of celiprolol and 100 mg of atenolol in this placebo-controlled, double-blind crossover study. Pulmonary function was assessed by spirometry. Changes in forced one-second expiratory volume (FEV1) and mid-maximal expiratory flow (MMEF) following both doses of celiprolol were indistinguishable from the effects of placebo, whereas atenolol caused a significant reduction in both measurements of pulmonary function. Graded doses of albuterol, a beta 2-selective sympathomimetic administered at 15-min intervals starting 3 h after each treatment, as expected, caused bronchodilation. The overall bronchodilatory effects of this combined, beta-blocker plus albuterol treatment on pulmonary function were greatest after celiprolol 600 mg, followed in order by celiprolol 400 mg, placebo, and atenolol. Celiprolol 400 mg and 600 mg neither caused bronchoconstriction nor antagonized albuterol in this acute study. Because of its bronchosparing properties, even at high doses, celiprolol may offer an advantage over other, similar agents in the treatment of hypertension and angina in asthmatics. Dilevalol combines a nonselective blocking action on beta-receptors with selective beta 2-agonist activity. In this double-blind, three-way, crossover study, the effects of relatively high single doses of dilevalol (400 mg), metoprolol (200 mg), a placebo on pulmonary function and their interaction with isoproterenol (160 and 480 micrograms) were evaluated in 16 patients with reversible bronchial asthma [isoproterenol-induced increase in forced expiratory volume in 1 s (FEV1) of greater than or equal to 15%]. When the lowest or minimum values observed during the 2 h postdrug evaluation period were considered, there was no significant difference from baseline in the percentage change in FEV1 after placebo (-4.4%) and dilevalol (-10%), with the difference between these treatments not being statistically significant. However, following metoprolol, FEV1 decreased by 18.3%, a decrease significantly different (p less than 0.01), from baseline and from the effects of placebo (p less than 0.01), although not from dilevalol. Furthermore, following metoprolol, 7 of 16 patients (44%) showed a greater than or equal to 20% decrease in FEV1 as compared to only 3 patients (19%) following dilevalol and 1 patient (6%) following placebo. The effects of the three treatments on forced vital capacity (FVC) and maximal midexpiratory flow (MMEF) were qualitatively similar to those observed in FEV1. Both dilevalol and metoprolol similarly and significantly (p less than or equal to 0.01) inhibited the isoproterenol (160 and 480 micrograms) response in FEV1 as compared to placebo.(ABSTRACT TRUNCATED AT 250 WORDS) Cardioselectivity of a single oral dose of metoprolol oral osmotic (OROS) (14/190 mg) and atenolol (100 mg) was compared in 12 patients with reversible obstructive airway disease by assessing the dose-response curve to increasing doses of inhaled salbutamol. The beta-blocking activity of the two drugs, which was determined by measuring heart rate, blood pressure, and derived indexes at peak plasma drug levels, was similar. Both metoprolol and atenolol significantly reduced forced vital capacity and peak expiratory flow, with no difference between drugs. Atenolol but not metoprolol also significantly reduced forced expiratory volume in 1 second and specific airway conductance. Both metoprolol and atenolol shifted the dose-response curve of specific airway conductance to the right. The results indicate that the new OROS delivery system for metoprolol, which produces a relatively constant plasma drug level, provides a cardioselectivity comparable to or greater than that of atenolol at maximum plasma levels. We evaluated the effects of oral metoprolol, 200 mg daily, on cardiac and pulmonary function in 6 patients with chronic reversible airways obstruction and no cardiac dysfunction. The patients were clinically stable. In all patients, baseline forced expiratory volume in 1 second (FEV1) was less than 60% predicted, and increased at least 15% after isoproterenol inhalation. Resting control first pass right and left ventricular radionuclide ejection fractions were normal or only slightly depressed. Compared to placebo, metoprolol did not significantly affect FEV1 or forced vital capacity. Metoprolol did not significantly alter left or right ventricular ejection fraction, measured by first pass radionuclide technique. On patient experienced increased dyspnea on metoprolol, which was not accompanied by changes in clinical exam, spirometry, or ejection fraction. We conclude that metoprolol may be safely administered to a subset of stable patients with chronic reactive airways disease. nan The effects of oral practolol (Eraldin, I.C.I. Ltd) (300 mg) and acebutolol (Sectral, May & Baker Ltd) (300 mg) were compared in a placebo-controlled, crossover study in ten asthmatics. 2. Pulse rate, forced expiratory volume in one second (FEV1) and specific airways conductance were measured before and after a bronchodilator and the same procedure was repeated after taking acebutolol, practolol or placebo. 3. A mean increase in resting airways obstruction and reduction in bronchodilator response were evident with both drugs. The differences were statistically significant only after acebutolol for the logarithm of specific conductance. Mean plasma levels of the two drugs were similar. The response to both drugs was similar in the same patient and unrelated to severity of asthma. Mean reduction in resting pulse rate was statisitcally greater after acebutolol compared with placebo but not after practolol compared with placebo. 4. In any individual the beta-adrenoceptor blocking response is unpredictable and any beta-adrenoceptor blocking drug must be used with extreme caution in asthmatics.