Controlled-release metoprolol compared with atenolol in asthmatic patients: Interaction with terbutaline
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The β2-adrenoceptor mediated effects on ventilatory capacity, forced expiratory volume in one second (FEV1), forced ventilatory capacity (FVC), heart rate, and skeletal muscle tremor of a new controlled-release (CR) formulation of metoprolol1, 100 mg and 200 mg, and of atenolol2 tablets, 100 mg, were studied in eight asthmatic patients. The effects of single-dose treatment, including placebo as reference, were studied in a randomized, double-blind, cross-over design.
Starting 2 h after drug intake, four intravenous infusions containing increasing doses of terbutaline were given at 30-min intervals, followed by three doses of terbutaline inhalations.
Maximum plasma concentrations for both metoprolol and atenolol were achieved within the study period. The FEV1 measurements after terbutaline infusions and inhalations were significantly lower after atenolol than after either dose of metoprolol CR. This indicates less blockade of β2-adrenoceptors with metoprolol CR than with atenolol at maximum plasma concentrations.
The terbutaline-induced skeletal muscle tremor and increase in heart rate were less after atenolol than after either dose of metoprolol CR, also suggesting less interaction of metoprolol CR with β2-receptors.
Thus, the new CR formulation of metoprolol caused fewer adverse effects on β2-adrenoceptor mediated bronchodilatation than a clinically equivalent dose of atenolol.
Key wordscontrolled-release metoprolol atenolol terbutaline ventilatory capacity heart rate skeletal muscle tremor asthmatic patients
- 1.Johnsson G, Svedmyr N, Thiringer G (1975) Effects of intravenous propranolol and metoprolol and their interaction with isoprenaline on pulmonary function, heart rate and blood pressure in asthmatics. Eur J Clin Pharmacol 8: 175–180Google Scholar
- 2.Åström H (1975) Comparison of the effects on airway conductance of a new selective beta-adrenergic blocking drug, atenolol, and propranolol in asthmatic subjects. Scand J Respir Dis 56: 292–296Google Scholar
- 3.Thiringer G, Svedmyr N (1976) Interaction of orally administered metoprolol, practolol and propranolol with isoprenaline in asthmatics. Eur J Clin Pharmacol 10: 163–170Google Scholar
- 4.Vilsvik JS, Schaanning J (1976) Effect of atenolol on ventilatory and cardiac function in asthma. Br Med J 2: 453–455Google Scholar
- 5.Löfdahl C-G (1982) Selectivity of β-adrenoceptor agonists and antagonists in asthmatics. Eur J Respir Dis 63 [Suppl 120]: 1–53Google Scholar
- 6.Löfdahl C-G, Svedmyr K, Svedmyr N (1984) Selectivity of bevantolol hydrochloride, aβ 1-adrenoceptor antagonist, in asthmatic patients. Pharmacotherapy 4: 205–210Google Scholar
- 7.Löfdahl C-G, Svedmyr N (1981) Cardioselectivity of atenolol and metoprolol. A study in asthmatic patients. Eur J Respir Dis 62: 396–404Google Scholar
- 8.Sandberg A, Blomqvist I, Jonsson UE, Lundborg P (1988) Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: A comparison with conventional tablets. Eur J Clin Pharmacol 33 [Suppl]: S9–S13Google Scholar
- 9.Rydén L, Kristensson B-E, Westergren G (1988) Effect of controlled-release metoprolol on blood pressure and exercise heart rate in hypertension: A comparison with conventional tablets. Eur J Clin Pharmacol 33 [Suppl]: S33–S37Google Scholar
- 10.Blomqvist I, Westergren G, Sandberg A, Jonsson UE, Lundborg P (1988) Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: A comparison with atenolol. Eur J Clin Pharmacol 33 [Suppl]: S19–S24Google Scholar
- 11.Mason WD, Winer N, Kochak G, Cohen I, Bell R (1979) Kinetics and absolute bioavailability of atenolol. Clin Pharmacol Ther 25: 408–415Google Scholar
- 12.Thiringer G, Svedmyr N (1975) Evaluation of skeletal muscle tremor due to bronchodilator agents. Scand J Respir Dis 56: 93–102Google Scholar
- 13.Ervik M, Kylberg-Hanssen K, Lagerström P-O (1980) Electron-capture-gas chromatographic determination of atenolol in plasma and urine, using a simplified procedure with improved selectivity. J Chromatogr 182: 341–347Google Scholar
- 14.Ervik M, Kylberg-Hanssen K, Johansson L (1986) Determination of metoprolol in plasma and urine using high-resolution gas chromatography and electron-capture detection. J Chromatogr 381: 168–174Google Scholar
- 15.Löfdahl C-G, Marlin GE, Svedmyr N (1983) Pafenolol, a highly selective β1-adrenoceptor-antagonist, in asthmatic patients: Interaction with terbutaline. Clin Pharmacol Ther 33: 1–9Google Scholar
- 16.Miller RG Jr (1981) Simultaneous statistical inference, 2nd edn. Springer, Berlin Heidelberg New York, pp 67–70Google Scholar
- 17.Lyngstam O, Rydén L (1981) Metoprolol and atenolol administered once daily in primary hypertension. Acta Med Scand 209: 261–266Google Scholar
- 18.Wilcox RG, Hampton JR (1981) Comparative study of atenolol, metoprolol, metoprolol Durules, and slow-release oxprenolol in essential hypertension. Br Heart J 46: 498–502Google Scholar
- 19.Löfdahl C-G, Svedmyr N (1982) Effects of prenalterol in asthmatic patients. Eur J Clin Pharmacol 23: 297–302Google Scholar
- 20.Zaagsma J, van der Heijden PJCM, van der Schaar MWG, Bank CMC (1984) Differentiation of functional adrenoceptors in human and guinea pig airways. Eur J Respir Dis 135: 16–33Google Scholar
- 21.Barnes PJ, Carstairs JA, Nimmo AJ (1985) Visualization of beta-adrenoceptor subtypes in human lung. Am Rev Respir Dis 131 [Suppl 4]: A 387Google Scholar
- 22.Tattersfield AE, Harrison RN (1983) Effect of β-blocker therapy on airway function. Drugs 25 [Suppl 2]: 227–231Google Scholar
- 23.Claque HW, Ahmad D, Carruthers SG (1984) Influence of cardioselectivity and respiratory disease on pulmonary responsiveness to beta-blockade. Eur J Clin Pharmacol 27: 517–523Google Scholar
- 24.Thomas MS, Tattersfield AE (1986) Comparison of beta-adrenoceptor selectivity of acebutolol and its metabolite diacetolol with metoprolol and propranolol in normal man. Eur J Clin Pharmacol 29: 679–683Google Scholar
- 25.Riddell J, Shanks RG (1985) Effects of betaxolol, propranolol, and atenolol on isoproterenol-induced beta-adrenoceptor responses. Clin Pharmacol Ther 38: 554–559Google Scholar
- 26.Thiringer G, Svedmyr N (1975) Comparison of infused and inhaled terbutaline in patients with asthma. Scand J Respir Dis 57: 17–24Google Scholar
- 27.Robinson BF, Epstein SE, Beiser GD, Braunwald E (1966) Control of heart rate by the autonomic nervous system. Circ Res 19: 400–411Google Scholar
- 28.Arnold JMO, McDevitt DG (1983) Heart rate and blood pressure responses to intravenous boluses of isoprenaline in the presence of propranolol, practolol and atropine. Br J Clin Pharmacol 16: 175–184Google Scholar
- 29.Brown JE, McLeod AA, Shand DG (1983) Evidence for cardiac β2-adrenoceptors in man. Clin Pharmacol Ther 33: 424–428Google Scholar
- 30.Zerkowski H-R, Ikezono K, Rohm N, Reidemeister JC, Brodde O-E (1986) Human myocardial β-adrenoceptors: Demonstration of both β1-and β2-adrenoceptors mediating contractile responses to β-agonists on the isolated right atrium. Naunyn Schmiedebergs Arch Pharmacol 332: 142–147Google Scholar
- 31.Larsson S, Svedmyr N (1977) Tremor caused by sympathomimetics is mediated by beta2-adrenoceptors. Scand J Respir Dis 58: 5–10Google Scholar
- 32.Perucca E, Pickles H, Richens A (1981) Effect of atenolol, metoprolol, and propranolol on iso-proterenol-induced tremor and tachycardia in normal subjects. Clin Pharmacol Ther 29: 425–433Google Scholar