Enalapril and diltiazem co-administration and respiratory side effects of enalapril.
Journal Title: Physiological Research - Year 2005, Vol 54, Issue 6
Abstract
Persistent, chronic dry cough is the most common adverse effect of angiotensinconverting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is relatedto the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and other inflammatoryneuropeptides in the airways. The aim of this study was to follow the relationship between 15-day administrationof enalapril and the defence reflexes (cough and bronchoconstriction) of the airways in experimentalanimals, as well as possibility of their pharmacological restriction with simultaneous diltiazem administration.Cough reflex was investigated by the method of mechanical irritation of laryngopharyngeal and tracheobronchialarea in non-anaesthetized cats. Reactivity of the tracheal smooth muscle of the airways to the bronchoconstrictormediators (histamine 10nM-1mM, acetylcholine 10nM-1mM and KCl 1mM-100mM) was evaluated by in vitro methodin guinea pigs. Enalapril 5 mg/kg/day and diltiazem 30 mg/kg/day were administered perorally for 15 days.Results showed that long-lasting administration of enalapril resulted in a significant increase of measuredcough parameters and increased reactivity of tracheal smooth muscle to the histamine and KCl. Simultaneousadministration of enalapril together with diltiazem significantly decreased the enalapril induced cough,and decreased enalapril induced hyperreactivity of the tracheal smooth muscle to the KCl. The resultsshowed a partially protective effect of diltiazem and enalapril coadministration on the respiratory adverseeffects induced by enalapril therapy.
Authors and Affiliations
M Antošová, G Nosáľová, S Fraňová
Keywords
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