Anticholinergic agents in asthma and COPD

doi:10.1016/j.ejphar.2005.12.072

European Journal of Pharmacology

Volume 533, Issues 1–3, 8 March 2006, Pages 36-39

https://doi.org/10.1016/j.ejphar.2005.12.072 Get rights and content

Abstract

Anticholinergic agents have important uses as bronchodilators for the treatment of obstructive airway diseases, both asthma and, more particularly, chronic obstructive pulmonary disease (COPD). Those in approved clinical use are synthetic quaternary ammonium congeners of atropine, and include ipratropium bromide, oxitropium bromide, and tiotropium bromide, each of which is very poorly absorbed when given by inhalation. Ipratropium and oxitropium have relatively short durations of action (4–8 h). They have been widely used for many years, either alone or in combination with short-acting beta-adrenergic agents such as albuterol and fenoterol, for both maintenance treatment of stable disease and for acute exacerbations of airway obstruction. Tiotropium, which was introduced in the early 2000s, has a duration of action of at least 1–2 days making it suitable for once-daily maintenance treatment of COPD. All of the above agents have a wide therapeutic margin and are safe and well tolerated by patients.

Introduction

Although naturally occurring anticholinergic alkaloids such as atropine and scopolamine have been used in traditional medical cultures for many years, these agents are well absorbed into the systemic circulation and thus have multiple systemic side-effects that limit their clinical usefulness. The discovery that synthetic quaternary congeners of atropine were very poorly absorbed but retained topical anticholinergic activity enabled the development of analogues of atropine such as ipratropium, oxitropium, and tiotropium bromides for clinical use as inhaled bronchodilators. In the last 2 decades, these agents have become important agents in the routine treatment of COPD but also for asthma in certain circumstances.

Section snippets

Available agents

In most countries, ipratropium bromide is available as a metered-dose inhaler, as a dry powder inhalation, and as a nebulizable solution as Atrovent®. Because the original dose of ipratropium, 40 μg, is suboptimal for COPD (Gross et al., 1989), a double strength metered-dose inhaler form, Atrovent forte®, is also available in many countries outside the USA. Fixed combinations of ipratropium with albuterol (salbutamol) are also available in metered-dose inhaler form as Combivent® and in

Stable COPD

The major clinical use of inhaled anticholinergic agents is for the routine treatment of stable COPD. Several large multi-center long-term clinical studies in the 1980s compared ipratropium metered-dose inhaler with a β-adrenoreceptor agonist metered-dose inhaler. These uniformly showed that the increase in Forced Expired Volume in 1 s (FEV₁), the primary outcome of the studies, was at least as great and as prolonged with ipratropium as with a conventional β-adrenoreceptor agonist and sometimes

Side-effects and adverse events

Being very poorly absorbed, currently approved inhaled anticholinergic agents have a very wide therapeutic margin and are very well tolerated, even in rare instances when massive doses have accidentally been given (Gross and Skorodin, 1985). In normal clinical use, dryness of the mouth is a common side effect of all agents in this class but is rarely sufficiently severe for the patient to discontinue use. Bad taste is an occasional complaint, as is a brief coughing spell shortly after

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ReviewAnticholinergic agents in asthma and COPD

Abstract

Introduction

Section snippets

Available agents

Stable COPD

Side-effects and adverse events

Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study

JAMA

Preservatives in nebulizer solutions: risks without benefit

Pharmacotherapy

Possible association of benzalkonium chloride in nebulizer solutions with respiratory arrest

Ann. Pharmacother.

Assessment of the clinical usefulness of nebulised ipratropium bromide in patients with chronic airflow limitation

Thorax

Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD

Thorax

A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease

Eur. Respir. J.

Standards for the diagnosis and treatment of patients with COPD; a summary of the ATS/ERS position paper

Eur. Respir. J.

The protective effect of inhaled Sch1000 MDI on bronchoconstriction induced by serotonin, histamine, acetylcholine and propanaolol

Postgrad. Med. J.

Ba 679 BR, a novel long-acting anticholinergic bronchodilator

Life Sci.

Ipratropium bromide

N. Engl. J. Med.

Tiotropium bromide

Chest

Anticholinergic, antimuscarinic bronchodilators

Am. Rev. Respir. Dis.

Role of the parasympathetic system in airway obstruction due to emphysema

N. Engl. J. Med.

Massive overdose of atropine methonitrate with only slight untoward effects

Lancet

Dose response to ipratropium as a nebulized solution in patients with chronic obstructive pulmonary disease. A three-center study

Am. Rev. Respir. Dis.

Review
Anticholinergic agents in asthma and COPD