17.01.4.1 β2-adrenoceptor agonists

Adrenaline is a hormone released from adrenal medulla that has widespread effects including stimulating bronchial b₂-adrenoceptors to induce bronchodilation via cell-signaling involving adenylate cyclase (eChapter 7). Salbutamol is a short-acting and salmeterol is a long-acting selective b₂-adrenoceptors agonist. Both salbutamol and salmeterol stimulate b₂-adrenoceptors to cause relaxation of bronchial smooth muscle, and both are used clinically as bronchodilators in asthma, but they are used in different ways.

Salbutamol is a short acting selective b₂-adrenoceptor agonist, which is inhaled for the symptomatic relief of an asthma attack (dyspnea - shortness of breath) on an as needed basis. Thus, it is only used when an attack of asthma occurs, and salbutamol is quick acting. There is an onset of action within a few minutes, and the bronchodilation continues for 3-4 hours. In the emergency treatment of asthma, it may be necessary to use doses of salbutamol that are higher than in the normal salbutamol inhaler. Thus, in the emergency treatment of asthma, salbutamol can be delivered in a nebuliser. Nebulisers produce fine droplets in the air (aerosol), and are used to deliver large doses of drugs (in this case, salbutamol) in an emergency.

When the symptoms of asthma become persistent, subjects are not being managed well with salbutamol alone, and the treatment has to be re-evaluated and prophylactic (preventative) treatment may be indicated. Salmeterol is a long lasting selective b₂-adrenoceptor agonist (LABA). It is used as a chronic regular inhalation for a prophylactic effect in asthma i.e. ongoing bronchodilation to prevent an asthma attack. Salmeterol has a slow onset of action, which makes it unsuitable for use in acute attacks of asthma. Salmeterol has a duration of action of greater than 12 hours, and is usually used as an inhalation, either once or twice a day. It has been shown that the chronic use of salmeterol improves lung function, decreases asthma symptoms, decreases nocturnal asthma and also decreases the use of short acting b₂- adrenoceptor agonists. Thus, asthmatics continue to carry their salbutamol inhalers for use in asthma attacks, but when they are taking salmeterol, there are less asthma attacks, and less use of short acting b₂- adrenoceptor agonists.

However, long term use of salmeterol is associated with increased risk of asthma exacerbations and death. Thus, it is not introduced into the treatment of asthma, unless it has been shown that a maximum dose of glucocorticoid is ineffective alone. If the maximum dose of glucocorticoid alone does not prevent exacerbation, salmeterol may be introduced, as in this situation the benefits of salmeterol outweighs the risks of salmeterol. Salmeterol is used in combination with a glucocorticoid in a single inhaler, as use of a single inhaler improves adherence to the asthma medicine, and the control of the asthma.

As both salbutamol and salmeterol are β₂-adrenoceptor selective, not specific, the side effects of high doses included b₁-adrenoceptor mediated increase in heart rate, sometimes leading to cardiac arrhythmias. b₂-Adrenoceptor agonists are used in the treatment of COPD, but their beneficial effect is marginal.