Effects of nonsedating antihistamine, astemizole, on the in situ canine heart assessed by cardiohemodynamic and monophasic action potential monitoring.
Toxicol Appl Pharmacol
; 143(1): 89-95, 1997 Mar.
Article
em En
| MEDLINE
| ID: mdl-9073596
ABSTRACT
The possible mechanisms of cardiac adverse effects of astemizole were studied using a halothane-anesthetized in vivo canine model under the cardiohemodynamic and monophasic action potential monitoring. A dose of 0.3 mg/kg of iv astemizole (n = 7), which is close to the recommended dose for clinical use, showed a bradycardic effect and a reversed use-dependent lengthening of repolarization. The increase in the repolarization was greater than in the effective refractory period. These effects persisted even when the plasma drug concentration became undetectable. Additional administration of 3.0 mg/kg of iv astemizole (n = 7) decreased the mean blood pressure, suppressed the cardiac contraction and conduction, and induced early after depolarization-like potential in addition to the qualitatively similar effects compared to those observed by the lower dose. The decrease of the plasma concentration of astemizole followed the pattern predicted by the two-compartment theory of pharmacokinetics, but the drug concentration in the cardiac muscle was estimated to be more than 100 times greater than that in plasma. Our study emphasizes that each cardiac consequence of astemizole overdose may be related to proarrhythmic effects and the monitoring of plasma drug concentration will be less helpful in predicting the cardiac adverse effects of astemizole. The results provide some insights into the clinical cardiotoxicity of astemizole. Drugs or interventions inducing positive chronotropic, inotropic, and dromotropic effects can become good candidates for the treatment of astemizole intoxication, which may attenuate the cardiac effects of astemizole including the lengthening of repolarization.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
/
Astemizol
/
Coração
/
Hemodinâmica
/
Antagonistas dos Receptores Histamínicos H1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Japão