Title:Inhaled Muscarinic Acetylcholine Receptor Antagonists for Treatment of COPD
VOLUME: 20 ISSUE: 12
Author(s):P. Montuschi, F. Macagno, S. Valente and L. Fuso
Affiliation:Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo Francesco Vito, 1 00168 Rome, Italy.
Keywords:Inhaled anticholinergic antimuscarinic drugs, muscarinic receptors, inhaled muscarinic receptor antagonists, tiotropium
bromide, ipratropium bromide, long-acting antimuscarinic agents, long-acting beta-agonists, inhaled corticosteroids,
chronic obstructive pulmonary disease
Abstract:Bronchodilators, generally administered via metered dose or dry powder inhalers, are the mainstays of pharmacological
treatment of stable COPD. Inhaled long-acting beta-agonists (LABA) and anticholinergics are the bronchodilators
primarily used in the chronic treatment of COPD. Anticholinergics act as muscarinic acetylcholine receptor antagonists
and are frequently preferred over beta-agonists for their minimal cardiac stimulatory effects and greater efficacy in
most studies. Their therapeutic efficacy is based on the fact that vagally mediated bronchoconstriction is the major reversible
component of airflow obstruction in patients with COPD. However, bronchodilators are effective only on the reversible
component of airflow obstruction, which by definition is limited, as COPD is characterized by a fixed or poorly
reversible airflow obstruction. Inhaled anticholinergic antimuscarinic drugs approved for the treatment of COPD include
ipratropium bromide, oxitropium bromide and tiotropium bromide. Ipratropium bromide, the prototype of anticholinergic
bronchodilators, is a short-acting agent. Oxitropium bromide is administered twice a day. Tiotropium bromide, the only
long-acting antimuscarinic agent (LAMA) currently approved, is administered once a day. Newer LAMAs including
aclidinium bromide and glycopyrrolate bromide are currently in phase III development for treatment of COPD. Some new
LAMAs, including glycocpyrrolate, are suitable for once daily administration and, unlike tiotropium, have a rapid onset of
action. New LAMAs and their combination with ultra-LABA and, possibly, inhaled corticosteroids, seem to open new
perspectives in the management of COPD. Dual-pharmacology muscarinic antagonist-beta2 agonist (MABA) molecules
present a novel approach to the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a single
molecule.
