| Disodium cromoglycate does not prevent terbutaline-induced desensitization of beta 2-adrenoceptor-mediated cardiovascular in vivo functions in human volunteers. | |
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MedLine Citation:
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PMID: 10226872 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In humans, prolonged administration of the beta 2-adrenoceptor agonist terbutaline leads to a desensitization of beta 2-adrenoceptor-mediated cardiovascular responses, which can be blunted by concomitant administration of the antianaphylactic drug ketotifen. This study investigated the effect of disodium cromoglycate, another antiallergic drug, on terbutaline-induced desensitization of beta-adrenoceptor-mediated cardiovascular and noncardiovascular responses. In a double-blind, placebo-controlled, randomized design, nine healthy male volunteers received disodium cromoglycate (4 x 200 mg/day, p.o.) or placebo for 3 weeks with terbutaline (3 x 5 mg/day, p.o.) administered concomitantly during the last 2 weeks. beta 2-Adrenoceptor cardiovascular function was assessed by the increase in heart rate and reduction of diastolic blood pressure induced by an incremental intravenous infusion of the unselective beta-adrenoceptor agonist isoprenaline; beta 1-adrenoceptor cardiovascular function was assessed by exercise-induced tachycardia. Tremulousness was monitored as a beta 2-adrenoceptor-mediated noncardiovascular effect. After 2 weeks' administration of terbutaline, there was a marked and significant (p < 0.001) attenuation of isoprenaline-induced tachycardia (mean percentage attenuation, 53.3%) and of the isoprenaline-induced decrease in diastolic blood pressure (mean percentage attenuation, 55.6%). Exercise-induced tachycardia also was significantly (p < 0.001) blunted, but the magnitude of this attenuation was only very small (mean attenuation, 5.6%). Disodium cromoglycate affected neither the rightward shift of beta 2-adrenoceptor-mediated responses nor the small rightward shift in beta 1-adrenoceptor-mediated exercise tachycardia after 2 weeks' administration of terbutaline. Tremulousness observed during the first few days of terbutaline administration disappeared after 4 to 8 days, indicating development of desensitization of beta 2-adrenoceptor-mediated noncardiovascular responses. This was not prevented by disodium cromoglycate. These results confirm that long-term beta 2-adrenoceptor agonist therapy leads to a desensitization of beta 2-adrenoceptor-mediated cardiovascular and noncardiovascular effects in humans in vivo. However, unlike ketotifen, cromolyn sodium is not able to attenuate this desensitization. |
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Authors:
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R F Schäfers; U Piest; C von Birgelen; J Jakubetz; A E Daul; T Philipp; O E Brodde |
Publication Detail:
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Type: Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 33 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1999 May |
Date Detail:
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Created Date: 1999-06-11 Completed Date: 1999-06-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 822-7 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Essen, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Agonists
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adverse effects,
pharmacology* Adult Anti-Allergic Agents / pharmacology* Blood Pressure / drug effects Cromolyn Sodium / pharmacology* Drug Interactions Exercise Test Heart / drug effects*, physiology Heart Rate / drug effects Humans Isoproterenol / pharmacology Male Receptors, Adrenergic, beta-1 / physiology Receptors, Adrenergic, beta-2 / agonists, physiology* Terbutaline / adverse effects, pharmacology* Tremor / chemically induced, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Anti-Allergic Agents; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; 15826-37-6/Cromolyn Sodium; 23031-25-6/Terbutaline; 7683-59-2/Isoproterenol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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