Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Aug 15:761:168-73.
doi: 10.1016/j.ejphar.2015.05.020. Epub 2015 May 14.

Pharmacological interaction between LABAs and LAMAs in the airways: optimizing synergy

Luigino Calzetta  1 , Maria Gabriella Matera  2 , Mario Cazzola  3
Affiliations
Review

Pharmacological interaction between LABAs and LAMAs in the airways: optimizing synergy

Luigino Calzetta et al. Eur J Pharmacol. .

Abstract

Nowadays there is solid clinical information for combining β2-agonists and anti-muscarinic agents, although the nature (additive or synergistic) of the net clinical result obtained by co-administration of these two classes of bronchodilators is not completely elucidated from a pharmacological point of view. Recent preclinical studies demonstrated that combining a long-acting β2-agonist (LABA) with a long-acting anti-muscarinic agent (LAMA) provides synergistic benefit on airway smooth muscle relaxation, which may have major implications for the use of LABA/LAMA combinations in the treatment COPD. Indeed, the LABA/LAMA synergism has been proved also in patients with moderate-to-severe COPD. Nevertheless, there is still a strong medical need for dose-finding clinical trials designed to identify the most favourable doses of LABA/LAMA combinations able to induce a real synergism. We strongly believe that the Bliss Independence theory represents an effective model for investigating the cross-talk between β2-adrenoreceptor and the muscarinic pathways leading to the synergistic interaction between β2-agonists and anti-muscarinic agents. In any case, the possibility of eliciting a synergistic bronchodilator effect when combining a LABA and a LAMA suggests that the therapeutic approach proposed by GOLD recommendations to only use LABA/LAMA combination in more severe COPD patients who are not controlled by a single bronchodilator should be reconsidered. We support the possibility of an early intervention with low doses of LABA/LAMA combination to optimize bronchodilation and reduce the risk of adverse events that characterize both LABAs and LAMAs, especially when administered at the full doses currently approved for the treatment of COPD.

Keywords: Airways smooth muscle; COPD; Clinical trials; Drug interaction; Dual bronchodilation; LABA; LAMA; Translation research.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms

Substances