Enalapril and Diltiazem
Co-Administration and Respiratory Side Effects of Enalapril
S. FRAŇOVÁ, G. NOSÁĽOVÁ, M. ANTOŠOVÁ, S. NOSÁĽ
Department of Pharmacology, Jessenius Faculty of Medicine,
Comenius University,
Martin, Slovakia
Received February 9, 2004
Accepted November 30, 2004
On-line available January 10, 2005
Summary
A persistent, chronic dry cough is the most common adverse
effect of angiotensin converting enzyme (ACE) inhibitors
therapy. The mechanism of this respiratory adverse effect is
related to the inhibition of ACE and the accumulation of
bradykinin, substance P, prostanoids and other inflammatory
neuropeptides in the airways. The aim of this study was to
follow the relationship between 15-day administration of
enalapril and the defense reflexes (cough and
bronchoconstriction) of the airways in experimental animals, as
well as the possibility of their pharmacological restriction
with simultaneous diltiazem administration. Cough reflex was
investigated by the method of mechanical irritation of
laryngopharyngeal and tracheobronchial area in non-anesthetized
cats. The reactivity of tracheal smooth muscles of the airways
to bronchoconstrictor mediators (histamine 10 nM – 1 mM,
acetylcholine 10 nM – 1 mM and KCl 1 mM – 100 mM) was evaluated
by an in vitro method in guinea pigs. Enalapril 5 mg/kg/day and
diltiazem 30 mg/kg/day were administered perorally for 15 days.
The results showed that long-lasting administration of enalapril
resulted in a significant increase of measured cough parameters
and increased reactivity of tracheal smooth muscle to histamine
and KCl. Simultaneous administration of enalapril together with
diltiazem significantly decreased the enalapril induced cough,
and decreased enalapril induced hyperreactivity of tracheal
smooth muscles to KCl. The results showed a partially protective
effect of diltiazem and enalapril co-administration on the
respiratory adverse effects induced by enalapril therapy.
Key words
Enalapril • Cough • Bronchoconstriction • Diltiazem
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