Bronchodilators

Bronchodilators relax airway smooth muscle and widen the airways, lowering airflow resistance in asthma, chronic obstructive pulmonary disease (COPD) and other obstructive airway disorders. They relieve symptoms and improve lung function but do not suppress airway inflammation or change the long-term course of disease. The inhaled route is preferred because it gives a high airway dose with low systemic exposure.

Classification. Beta 2 agonists (short acting, long acting, ultra long acting), muscarinic antagonists (short acting, long acting) and methylxanthines (theophylline, aminophylline). Magnesium sulphate is a bronchodilator used only as an adjunct in severe acute asthma.

Mechanism. Beta 2 agonists raise cyclic AMP through Gs-coupled receptors and lower intracellular calcium. Muscarinic antagonists block M3 receptors, removing vagal cholinergic tone and reducing gland secretion. Methylxanthines inhibit phosphodiesterases and antagonise adenosine receptors.

Pharmacodynamics. Beta 2 agonists oppose any bronchoconstrictor stimulus and act within minutes. Cholinergic tone is the main reversible component in COPD, so antimuscarinics perform well there. The two classes act on different receptors and their effects add together.

Delivery. Pressurised metered dose inhaler with spacer, dry powder inhaler, soft mist inhaler and nebuliser are all effective when used correctly. Dry powder devices need adequate inspiratory flow, which may fail in severe exacerbation, young children and frail older adults. Where commercial spacers are unavailable, a clean 500 mL plastic bottle fitted to the inhaler is a workable low-cost substitute.

Key differences. Formoterol is the only agent combining onset within minutes with 12 hour duration, which allows reliever use when it is combined with an inhaled corticosteroid. Salmeterol is too slow for acute relief. As single agents for preventing COPD exacerbations, long acting antimuscarinics are preferred to long acting beta 2 agonists.

Selectivity. Beta 2 selectivity is relative and is lost at high dose, so tachycardia and arrhythmia become dose limiting.

Methylxanthines. Theophylline is a late add-on because the therapeutic window is narrow (serum level 10 to 20 mg/L, or 55 to 110 micromol/L) and interactions are many.

Asthma. A short acting beta 2 agonist relieves symptoms but leaves airway inflammation untreated, so it is not advised as sole therapy in adults and adolescents. A long acting beta 2 agonist is never given without an inhaled corticosteroid.

COPD. Start with a long acting antimuscarinic or a long acting beta 2 agonist, and move to both together if breathlessness persists. Adding an inhaled corticosteroid is favoured when exacerbations continue and the blood eosinophil count is 300 cells/microlitre or more, and argued against when the count is under 100 cells/microlitre.

Acute exacerbation. Salbutamol 4 to 10 puffs of 100 mcg through a spacer, or 2.5 to 5 mg nebulised, repeated every 20 minutes during the first hour in severe asthma. Add ipratropium 500 mcg nebulised in severe asthma and in COPD exacerbation.

Oxygen and nebulisers. In COPD with a risk of hypercapnia, drive the nebuliser with compressed air and give nasal oxygen to keep saturation at 88 to 92 percent. In asthma the usual saturation target is 93 to 95 percent.

Other use. Nebulised salbutamol 10 to 20 mg lowers serum potassium in hyperkalaemia, as an adjunct to insulin with glucose.

Adverse effects. Beta 2 agonists cause tremor, palpitations, tachycardia, headache and muscle cramps. High or repeated doses cause hypokalaemia, hyperglycaemia, hyperlactataemia and QT prolongation. Antimuscarinics cause dry mouth, constipation, urinary retention and, rarely, acute angle closure glaucoma when nebulised drug reaches the eye. Any inhaled product can cause paradoxical bronchospasm.

Cautions. Ischaemic heart disease, tachyarrhythmia, thyrotoxicosis, hypertension, diabetes and hypokalaemia for beta 2 agonists. Prostatic hypertrophy, bladder outlet obstruction and narrow angle glaucoma for antimuscarinics.

Interactions. Non-selective beta blockers antagonise beta 2 agonists and can precipitate severe bronchospasm; they are contraindicated in asthma. Loop and thiazide diuretics, systemic corticosteroids and theophylline add to hypokalaemia. Two antimuscarinics together add anticholinergic burden without extra benefit.

Monitoring. Reliever use more than twice weekly in asthma signals poor control. Check inhaler technique at every visit, heart rate, and serum potassium after repeated high dose treatment. Spirometry confirms response in COPD.

Special groups. Pregnancy: short acting and long acting beta 2 agonists and antimuscarinics may be continued, because uncontrolled asthma harms the foetus more than the drugs. Older adults: tremor, tachyarrhythmia and urinary retention are more likely; start low. Renal impairment: tiotropium is renally cleared, so watch for anticholinergic effects when creatinine clearance is under 60 mL/min. Children: spacer with face mask in young children.

Referral and escalation. Admit when there is no clear response to repeated bronchodilator doses, peak flow under 50 percent of best or predicted, or need for treatment more often than every 4 hours. Peak flow under 33 percent, silent chest, cyanosis, exhaustion, confusion or oxygen saturation under 92 percent is life threatening and needs senior and intensive care review.