Short-acting beta2 agonist (SABA) - An as required medication that can continue to be used at all treatment stages. Rapid onset (15mins) with effects lasting up to 4 hours.

 

Mechanism of action: Within the smooth muscle of the bronchi, GI tract, uterus and blood vessels are beta-2-receptors. Activation of these G-protein-coupled receptors leads to relaxation of smooth muscle, relaxing constricted airways, improving airflow and so reducing breathlessness.

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Salbutamol (off-label use)

• Aerosol inhalation — 100 micrograms to 200 micrograms (1–2 puffs) up to four times daily.

• Dry powder inhalation — 200 micrograms to 400 micrograms up to four times daily.

• Nebulized solution — 2.5 mg to 5 mg, up to four times daily, or more frequently (to a maximum of 40 mg daily) in severe cases.

Pharmacodynamics: A selective beta-2-adrenoceptor agonist, which at therapeutic doses acts on bronchial muscle providing short-acting bronchodilation (around 4-6hours) at a fast onset (5minutes) in reversible airway obstruction.

Pharmacokinetics: When using the inhaled route 10-20% reaches the lower airways, the rest is deposited in the oropharynx and swallowed. From the lower airways it is absorbed into pulmonary tissues and circulation, but is not metabolised in the lungs. After reaching systemic circulation it goes through hepatic metabolism and excreted in the urine as unchanged drug and as the phenlolic sulfate. Most of the dose is excreted within 72hours. Salbutamol can bind to plasma proteins at around 10%.

 

Terbutaline sulfate (off-label use)

• Dry powder inhalation — 500 micrograms (1 inhalation) up to four times daily.

• Nebulized solution — 5 mg to 10 mg two to four times daily.

Pharmacodynamics: A selective beta-2-adrenoceptor agonist relaxing bronchial smooth muscle. It has a antiallergic effect on mast cells, inhibiting bronchoconstrictor mediators from being released (e.g. histamine, neutrophil chemotactic factor (NCF). It also increases mucocillary clearance. It has a duration of 6hours in most patients.

Pharmacokinetics: Less than 10% of the dose is absorbed from the airways, the other 90% does not enter systemic circulation due to extensive first-pass metabolism. About 90% of the drug is excreted in urine as inactive conjugates and unchanged drug, the ratio varies depending on route of administration.

 

Combination products:

• Combivent® nebuliser solution (salbutamol 2.5 mg plus ipratropium bromide 500 micrograms)

• Salipraneb (0.5mg ipratropium, 2.5mg salbutamol) — 2.5 mL (one vial) three or four times daily. Licensed for the treatment of bronchospasm in people with COPD.

 

Cautions:

• Hyperthyroidism — beta-2 agonists may stimulate thyroid activity.

• Diabetes mellitus — there is a rare risk of ketoacidosis (especially after intravenous beta-2 agonist administration). Additional blood glucose measurements are recommended when treatment with a beta-2 agonist is commenced.

• Cardiovascular disease (including hypertension) — beta-2 agonists may cause an increased risk of arrhythmias and significant changes to blood pressure and heart rate.

• Susceptibility to QT-interval prolongation.

• Hypokalaemia — plasma potassium concentration may be reduced by beta-2 agonists (particularly high doses).

• Convulsive disorders

 

Side-effects: Due to activation of beta-2-receptors in other tissues there are common ‘fight or flight’ effects of tachycardia, palpitations, anxiety and tremor. They promote glycoogenolysis and may increase serum glucose. At high doses serum lactate levels may also rise.

 

Interactions:

• Corticosteroids, diuretics, and theophylline — can cause hypokalaemia (particularly at high doses), which can be increased by other potassium-depleting drugs  (e.g. corticosteroids, loop diuretics, and theophylline), monitor potassium levels.

• Digoxin — monitor potassium levels and be alert to signs of digoxin toxicity, such as loss of appetite, nausea, vomiting, bradycardia, visual disturbance, and drowsiness.