Respiratory - Beta2-agonists: salbutamol, salmeterol, formoterol, terbutaline

Question 1

Compound (β2-agonist–corticosteroid) inhalers: Seretide®, Symbicort®

Commom Indications

Answer 1

Asthma:

• control of symptoms and prevention of exacerbations, used at ‘steps 3–4’ in the management of chronic asthma.

Chronic obstructive pulmonary disease (COPD):

• to control symptoms and prevent exacerbations in patients who have severe airflow obstruction on spirometry and/or recurrent exacerbations

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.

Question 2

Mechanisms of action

Answer 2

• 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.

Question 3

Important adverse effects

Answer 3

• Activation of β2-receptors in other tissues accounts for the common ‘fight or flight’ adverse effects of tachycardia, palpitations, anxiety and tremor.
• They also 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.

Question 4

Warnings

Answer 4

• 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.

Question 5

Important interactions

Answer 5

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

Question 6

Practical prescribing

Answer 6

• Inhaled short-acting β2-agonists are prescribed for ‘as required’ administration.
• A common choice in adults is salbutamol 100–200 micrograms inhaled as required.
• In asthma and COPD exacerbations requiring hospital treatment, nebulised therapy is more often used (e.g. salbutamol 2.5 mg nebulised 4-hrly; see Clinical tip), although inhalation via a spacer is reasonable provided the exacerbation is not life threatening.
• Long-acting β2-agonists are used for maintenance therapy and are therefore prescribed regularly (usually twice daily).
• To assure co-administration with a steroid in asthma, they may be prescribed as part of a combination inhaler (e.g. Symbicort® or Seretide®, usually prescribed by brand name).
• These combinations are also used in COPD, where they can improve convenience.