Adrenoceptor agonists inhalant bronchodilators

Methacholine is used to identify bronchial hyperreactivity in patients without clinically apparent asthma. For this indication, the drug is administered by inhalation, and patients who may be developing asthma usually produce an exaggerated airway contraction. Upon completion of the test, a rapid-acting bronchodilator (e.g., inhaled p-adrenoceptor agonist) can be given to counter the bronchoconstrictor effect of methacholine and relieve the patient s discomfort. 

D. In all asthma treatment regimens, inhaled 2-adrenoceptor agonists are used as bronchodilators as needed to relieve acute symptoms. As asthma is an inflammatory disease of the airway, inhaled corticosteroids are also used as standard therapy to control symptoms in all but the mildest cases. The potential for dangerous side effects and drug... 

The drugs most used for management of asthma are adrenoceptor agonists, or sympathomimetic agents (used as "relievers" or bronchodilators) and inhaled corticosteroids (used as "controllers" or anti-inflammatory agents). Their basic pharmacology is presented in detail elsewhere (see Chapters 9 and 39). In this chapter, we review their pharmacology relevant to asthma. 

Fears that heavy use of E-agonist inhalers could actually increase morbidity and mortality have not been borne out by careful epidemiologic investigations. Heavy use most often indicates that the patient should be receiving more effective prophylactic therapy with corticosteroids. In general, 62-adrenoceptor agonists are safe and effective bronchodilators when given in doses that avoid systemic adverse effects. 

Bronchodilation. p2-Adrenoceptor-medi-ated bronchodilation plays an essential part in the treatment of bronchial asthma and chronic obstructive lung disease (p.340). For this purpose, p2-agonists are usually given by inhalation preferred agents being those with low oral bioavailability and low risk of systemic unwanted effects (e. g., feno-terol, salbutamol, terbutaline). 

Q6 Salbutamol is a selective beta-2-adrenoceptor (/ -adrenoceptor) agonist which is effective in relieving mild to moderate bronchoconstriction. Inhalation of salbutamol induces bronchodilation by acting on /J2-receptors on bronchial smooth muscle this lasts for approximately three to five hours. It also inhibits mediator release and improves the clearance of mucus from the lung. Stimulation of the /02-receptor increases the cellular concentration of cyclic adenosine monophosphate cAMP and activates a protein kinase. This kinase in turn inactivates myosin-light-chain kinase, an enzyme necessary for contraction in smooth muscle, and so relaxes bronchial smooth muscle. 

The most commonly used bronchodUators are the beta-adrenoceptor agonists. In some patients, a muscarinic blocking drug (eg, ipratropium) has a useful bronchodilating effect. Cromolyn and nedocromil inhibit the degranulation of mast cells and are useful as prophylactic agents in some patients. They are not useful in an acute attack. Systemic corticosteroids are reserved for patients with severe asthma who do not respond adequately to other agents, but inhaled steroids (eg, beclomethasone) are standard prophylactic therapy for aU individuals with moderate or severe recurrent asthma... 

Nix et al. (1990) found the protective effect of formoterol against methacholine-induced broncho-constriction in 12 asthmatic patients lasting for at least 5 h. The rapid pulmonary absorption of inhaled formoterol and its slow elimination from plasma are in agreement with the fast onset and the long duration, respectively, of bronchodilation of inhaled formoterol fumarate in clinical trials (Le-CAiLLON et al. 1997). There was no indication that formoterol produced a more pronounced tachyphylaxis to P2-adrenoceptor stimulation in the bronchial muscle of asthmatics than the P2-adrenoceptor agonists normally used, e.g. salbutamol (Larsson et al. 1988, Arvidsson et al. 1989). Formoterol powder is as potent as solution (Clauzel et al. 1991). 

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