Anticholinergic Agents

Abstract

INTRODUCTIONsequences between the fifth and the sixth transmembrane regions is important in conveying speciThe parasympathetic nerves supplying the lung proficity of the muscarinic acetylcholine receptor for vide the dominant neuronal control of airway smooth G-protein recognition and exhibits high divergence muscle tone and are consequently likely to play a between the different subtypes. The cytoplasmic dopivotal role in the maintenance of homeostasis. It is main binds, recognizes and activates specific G-proequally likely, however, that dysfunction of these teins in an agonist-dependent manner. The activated, nerves might contribute to the pathogenesis of a GTP-liganded G-proteins then mediate a wide variety variety of pulmonary diseases. The event leading to of events. 4 Expression models have revealed that single nerve-induced contraction of airway smooth muscle muscarinic receptors of subtypes m 1 , m 3 or m 5 can involves the interaction of acetylcholine (ACh) at a activate multiple signalling effectors simultaneously, number of different cholinoceptors.

Atropine pretreatment enhances airway hyperreactivity in antigen-challenged guinea pigs through an eosinophil-dependent mechanism

“…During acute asthma, adding anticholinergic therapy to ␤-agonists rapidly improves pulmonary function, decreases rates of hospitalization by 50% (55), and decreases the duration of hospital stay by more than 1 day (3). However, use of anticholinergics in management of chronic stable asthma has been disappointing (4,30,31,35,69) and is not recommended by the National Institutes of Health Expert Panel on the Management of Asthma (48). This may in part be due to substantial underdosing, coupled with the nonselective nature of the muscarinic antagonists (67).…”

Pharmacology and Therapeutics of Bronchodilators

“…When administered via inhalation at therapeutic doses of 20 to 40 g, ipratropium bromide is somewhat less effective than SABAs in patients with asthma (Cazzola et al, 1998a) and less effective than LABAs in patients with COPD .…”

“…3). Chemical modifications of the atropine molecule, in particular by making its nitrogen atom pentavalent, have yielded a number of synthetic congeners that are very poorly absorbed from mucosae and cross the blood-brain barrier with difficulty, but in other respects they have pharmacological properties similar to those of atropine (Cazzola et al, 1998a;Gross, 2006). The quaternary structure of these anticholinergics prevents a substantial absorption from mucosal surfaces and penetration of the blood-brain barrier.…”

Current opinion: Pharmacological approaches in asthma and COPD

“…Small, early studies tend to favor the use of anticholinergics in asthma [16]. However a more recent Cochrane review concluded that overall there is no justifi cation for routinely introducing anticholinergics as part of add-on treatment for patients whose asthma is not well controlled on standard therapies [17].…”

“…Anticholinergics are less useful in asthma than in COPD, as inhaled  2 -agonists are generally more e ffective [16,30]. Nonetheless , it ha s been highlighted that there is considerable variation in responsiveness to an anticholinergic agent among asthmatic patients, with a few responding as well to it as to a  2 -agonist [31].…”