Salbutamol

Salbutamol is a short-acting selective beta-2 adrenoceptor agonist used as the usual rescue bronchodilator in asthma and COPD and as a temporising agent in hyperkalaemia. Inhaled onset is within 5 minutes, peak effect 15 to 30 minutes, duration 4 to 6 hours.

Classification. Short-acting beta-2 agonist (SABA), sympathomimetic bronchodilator.

Mechanism. Beta-2 stimulation raises cyclic AMP, relaxing airway smooth muscle and driving potassium into cells through Na+/K+-ATPase. It also relaxes uterine muscle.

Pharmacodynamics. Bronchodilation, tremor, tachycardia, fall in potassium, rise in glucose and lactate. Regular use causes tolerance to the bronchoprotective effect.

Pharmacokinetics. Only 10 to 20% of an inhaled dose reaches the lungs. The swallowed fraction undergoes gut-wall sulphation (oral bioavailability about 50%). Half-life 4 to 6 hours; renal excretion of unchanged drug and sulphate conjugate.

First-line, asthma relief. In adults and adolescents, usual practice is an inhaled corticosteroid with formoterol as the reliever. Where that is unavailable, give salbutamol 100 to 200 micrograms (1 to 2 puffs) inhaled as needed, always alongside a regular inhaled corticosteroid. Reliever use on more than 2 days each week signals poor control.

Exercise-induced bronchoconstriction. 200 micrograms inhaled 10 to 15 minutes before exercise.

COPD. 100 to 200 micrograms inhaled as needed, up to 4 times daily. Usual maximum outside acute care is 800 micrograms daily.

Emergency, acute asthma or COPD exacerbation, adults.

• Inhaler with spacer: 4 to 10 puffs of 100 micrograms, one puff at a time with 5 tidal breaths each, repeated every 20 minutes for the first hour, then every 1 to 4 hours.

• Nebuliser: 2.5 to 5 mg every 20 minutes for 3 doses, then every 1 to 4 hours as needed.

• Life-threatening asthma: continuous nebulisation 5 to 10 mg/hour. Drive with oxygen in asthma. In COPD with hypercapnic risk, drive with compressed air and give nasal oxygen to keep SpO2 at 88 to 92%.

Emergency, children. Inhaler with spacer 2 to 10 puffs of 100 micrograms every 20 minutes for the first hour. Nebuliser 2.5 mg under 5 years and 5 mg from 5 years, every 20 minutes for the first hour, then every 1 to 4 hours.

Hyperkalaemia, adjunct. 10 to 20 mg nebulised over 10 minutes with insulin and glucose, plus calcium if the ECG is abnormal. Onset about 30 minutes, fall in potassium about 0.5 to 1 mmol/L, duration about 2 hours. Not used alone. Avoid with active tachyarrhythmia or ischaemia.

Specialist, intravenous. For severe asthma not responding to inhaled treatment, in a monitored setting. Adults: loading 250 micrograms by slow injection over 10 minutes, then infusion 5 to 20 micrograms/minute titrated to response. Children: loading 15 micrograms/kg over 10 minutes (maximum 250 micrograms), then 1 to 2 micrograms/kg/minute.

Oral. 2 to 4 mg three or four times daily, maximum 32 mg daily; start at 2 mg in older adults. Rarely needed and not advised when the inhaled route is possible.

Titration. Inhaled doses are repeated to effect with no fixed titration. Loading and maintenance steps apply only to the intravenous route. Salbutamol is not used for preterm labour.

Contraindications. Hypersensitivity. Intravenous or oral use is unsuitable in tachyarrhythmia, unstable ischaemic heart disease or uncorrected severe hypokalaemia.

Serious adverse effects. Hypokalaemia, tachyarrhythmia, myocardial ischaemia, type B lactic acidosis with high or intravenous doses, paradoxical bronchospasm, angioedema. There is no boxed warning.

Common adverse effects. Tremor, palpitations, headache, cramps, restlessness.

Interactions. Non-selective beta-blockers antagonise the effect and may provoke bronchospasm. Loop and thiazide diuretics, corticosteroids and theophylline add to hypokalaemia, which raises digoxin toxicity. Monoamine oxidase inhibitors, tricyclic antidepressants and other sympathomimetics add cardiovascular effects.

Common prescribing errors. Salbutamol as the only therapy in persistent asthma. Confusing mg with micrograms when prescribing nebulised or intravenous doses. Repeated high doses without checking potassium. Oxygen-driven nebuliser in hypercapnic COPD.

Special groups.

• Pregnancy: inhaled use is acceptable and untreated asthma is the greater risk. Breastfeeding: compatible.

• Children: intravenous dosing is by weight. Older adults: higher risk of arrhythmia, so start low with oral use.

• Kidney impairment: no change for inhaled use; clearance falls in severe impairment, so monitor potassium with intravenous use. Liver impairment: no specific adjustment.

• East Africa: where commercial spacers are unavailable, a cleaned 500 mL plastic bottle can serve as a spacer. Nebulisers are often compressor-driven, which suits COPD.

Formulations. Inhaler 100 micrograms/actuation. Dry powder 200 micrograms/dose. Nebuliser solution 2.5 mg and 5 mg in 2.5 mL. Injection 500 micrograms/mL. Oral tablets and syrup.

Inhaler technique. Shake, breathe out, one slow inhalation with actuation, hold breath for 10 seconds, wait 30 to 60 seconds before the next puff.

Intravenous preparation. Dilute in glucose 5% or sodium chloride 0.9%, for example 5 mg in 500 mL gives 10 micrograms/mL. Use an infusion pump.

Baseline. Pulse, respiratory rate, SpO2, peak flow or spirometry, potassium when high-dose or intravenous use is planned.

Monitoring. Peak flow and SpO2 after each dose in acute care. Heart rate and ECG with intravenous use. Potassium and lactate within 1 to 2 hours of repeated high doses or when tachypnoea persists despite improving airflow.

Stop and reduce rules. Reduce frequency once improved. Stop or reduce for arrhythmia or chest pain. Replace potassium when under 3.5 mmol/L and treat urgently when under 3.0 mmol/L. Therapeutic drug monitoring is not used.

Referral and escalation. Escalate to high-dependency care for failure to improve after 1 hour of intensive treatment, silent chest, exhaustion, rising carbon dioxide or lactate.