β2-agonists

Key examples

• Salbutamol
• Salmeterol
• Formoterol
• Terbutaline

 

Common indications

1. Asthma: short-acting β2-agonists are used to relieve breathlessness. Long-acting β2-agonists are used as ‘step 3’ treatment for chronic asthma, but must always be given in combination with inhaled corticosteroids.
2. Chronic obstructive pulmonary disease (COPD): short-acting β2-agonists are used to relieve breathlessness. Long-acting β2-agonists are an option for second-line therapy of COPD.
3. Hyperkalaemia: nebulised salbutamol may be used as an additional treatment (alongside insulin, glucose and calcium gluconate) for the urgent treatment of a high serum potassium concentration.

 

Mechanisms of action

• Beta2-receptors are found in smooth muscle of the bronchi, gastrointestinal tract, uterus and blood vessels. Stimulation of this G protein-coupled receptor activates a signalling cascade that leads to smooth muscle relaxation. This improves airflow in constricted airways, reducing the symptoms of breathlessness. Like insulin, β2-agonists also stimulate Na+/K+-ATPase pumps on cell surface membranes, thereby causing a shift of K+ from the extracellular to intracellular compartment. This makes them a useful adjunct in the treatment of hyperkalaemia, particularly when IV access is difficult. However, their effect is less reliable than other therapies, so they should not be used in isolation.
• Beta2-agonists are classified as short-acting (salbutamol, terbutaline) or long-acting (salmeterol, formoterol) according to their duration of effect.

 

Important adverse effects

• Activation of β2-receptors in other tissues accounts for the common ‘fight or flight’ adverse effects of tachycardia, palpitations, anxiety and tremor. 
• They promote glycogenolysis, so may increase the serum glucose concentration. 
• At high doses, serum lactate levels may also rise. 
• Long-acting β2-agonists can cause muscle cramps.

 

Warnings

• Long-acting β2-agonists should be used in asthma only if an inhaled corticosteroid is also part of therapy. This is because, without a steroid, long-acting β2-agonists are associated with increased asthma deaths. 
• Care should be taken when prescribing β2-agonists for patients with cardiovascular disease, in whom tachycardia may provoke angina or arrhythmias. This is especially pertinent in the treatment of hyperkalaemia, when high doses may be necessary.

 

Important interactions

• Beta-blockers may reduce the effectiveness of β2-agonists. Concomitant use of high-dose nebulised β2-agonists with theophylline and corticosteroids can lead to hypokalaemia, so serum potassium concentrations should be monitored.