Respiratory drugs — bronchodilators
The following article was originally published as part the following CD ROM—National Respiratory Training Centre. Respiratory Therapeutics. Warwick: Education for Health, 2006. ISBN 1-904039-21-9.
Short-acting β2-agonists (SABAs)
These are fast-acting bronchodilators that can rapidly overcome bronchospasm.
They are sometimes called “β2 stimulants” because they are agonist drugs that bind with β2-adrenergic receptors stimulating bronchial smooth muscle to relax.
The most widely used bronchodilators are typically inhaled salbutamol (albuterol) and terbutaline.
They are used on demand in inhaled form for first-line relief therapy for both asthma and COPD patients. They may be the only medication needed for mild cases of both asthma and COPD.
They can also be delivered in high doses via a nebuliser or, as in secondary care, via intravenous infusion.
They are available in oral form, but oral β2 therapy is used infrequently in the UK.
They cause few side-effects at normal doses via the inhaled route. Side-effects are more common with oral therapy. High doses can cause a rapid pulse and palpitations and initially some patients may notice fine muscle tremor, particularly in the hands.
If used in high doses for long period they can affect potassium levels and produce hypokalaemia.
Long-acting β2-agonists (LABAs)
These are bronchodilators and are used for persistent asthma symptoms that are not controlled on inhaled steroids alone. They are also used for patients with chronic obstructive pulmonarydisease (COPD).
Normally they are used twice a day. Their effect lasts for 12 hours or longer.
Like short-acting β2-agonists they stimulate β2-adrenergic receptors. They achieve a long-acting effect by their ability to remain engaged with receptors for long periods. They bind to the receptor molecule in a way that stops them becoming easily detached.
Inhaled salmeterol and formoterol are the most commonly used forms of long acting β2 agonists.
Formoterol is a full agonist and salmeterol is a partial agonist.
They may have some additional anti-inflammatory effects, e.g. inhibiting the release of mediators by neutrophils, but are not licensed for this purpose.
Short-acting anticholinergics
Anticholinergics have an effect that is similar to that of the β2-agonist bronchodilators, but they achieve it by being antagonists.
Anticholinergics have a special role in treating COPD. Increased muscle tone in the airways (bronchomotor tone) is thought to play an important part in airflow obstruction in COPD and anticholinergic bronchodilators are effective in reducing this resting bronchomotor tone.
Ipratropium is the only available short acting anticholinergic and has an action lasting 4–6 hours. In combination with nebulised salbutamol it is advocated for the treatment of acute severe asthma.
Some patients with COPD achieve a better response with a combination of anticholinergics and β2-agonists than they do with either β2-agonists or anticholinergics alone.
The national clinical guideline on management of COPD in adults in primary and secondary care1 provides recommendations for the multi-disciplinary care of these patients.
Long-acting anticholinergics
Tiotropium is a long-acting anticholinergic. It remains bound to M receptors (M3) in bronchial smooth muscle for at least 24 hours. It is therefore used once daily. It is licensed only for use in COPD.
In clinical trials tiotropium has been shown to produce not only sustained improvements in lung function and symptoms, but also:
- Significant slowing of the rate of health status decline in COPD
- Reductions in exacerbation rates and hospital admissions
Methylxanthines
Alkaloids — theophylline, aminophylline and choline theophyllinate are alkaloids. Theophylline is the most commonly used.
They are believed to work by inhibiting phosphodiesterase resulting in increased levels of cyclic adenosine monophosphate (cAMP). cAMP is an important chemical agent in the cellular mechanism of smooth muscle contraction.
At high and even moderate doses they can produce significant side effects such as headache, nausea and cardiac arrhythmia. In addition sudden death has been reported with overdose.
They interact with a large number of commonly used medications, e.g. erythromycin and cimetidine and they have a narrow therapeutic window (10–20 mg/l).
They are available in either tablet form or via injection.
References
- Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax 2004; 59 (Suppl 1):1–232.
