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  • Title: Beta-adrenoceptor responses of the airways: for better or worse?
    Author: Broadley KJ.
    Journal: Eur J Pharmacol; 2006 Mar 08; 533(1-3):15-27. PubMed ID: 16469310.
    Abstract:
    Beta2-adrenoceptor agonists are the first-line treatment of asthma and chronic obstructive pulmonary disease (COPD), in which a short-acting beta2-adrenoceptor agonist is used as required for relief of bronchoconstriction. A long-acting beta2-adrenoceptor agonist may be added to an inhaled corticosteroid as step 3 in the management of chronic asthma. Long-acting beta2-adrenoceptor agonists may also be added in treatment of COPD. This review examines the beneficial and detrimental effects of beta2-adrenoceptor agonists. The beneficial effects of beta2-adrenoceptor agonists are mainly derived from their bronchodilator activity which relieves the bronchiolar narrowing and improves air flow. The potential anti-inflammatory actions of stabilizing mast cell degranulation and release of inflammatory and bronchoconstrictor mediators, is considered. Other potential beneficial responses include improvements in mucociliary clearance and inhibition of extravasation of plasma proteins that is involved in oedema formation in asthma. The side effects of beta2-adrenoceptor agonists are primarily related to beta2-adrenoceptor-mediated responses at sites outside the airways. Of major concern has been the development of tolerance and this is discussed in relation to incidence of increased morbidity and mortality to asthma over the past three decades. A clinical aspect of beta2-adrenoceptor pharmacology in recent years has been the recognition of genetic polymorphism of the receptor and how this affects responses to and tolerance to beta2-adrenoceptor agonists. A controversial feature of beta2-adrenoceptor agonists is their stereoisomerism and whether the inactive (S)-isomer of salbutamol had detrimental actions in the commercially used racemate. The consensus is that despite these adverse properties, beta2-adrenoceptor agonist remains the most useful pharmacological agents in the management of asthma and COPD.
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