Short-acting β2-agonists have a rapid onset of action and relieve symptoms for three to six hours. They should be used as short-term reliever therapy in all patients with symptomatic asthma and administered by inhalation as required rather than on a regular basis. Reduction in the duration of effect or an increase in use indicates poor control and treatment should be reviewed. In children, inhaled β2-agonists are more effective and have fewer side-effects than bronchodilator syrups, although occasional symptoms can be managed with oral therapy.
Long-acting β2-agonists can be used to improve symptom control, particularly at night or with exercise-induced symptoms, and are indicated for use on a long-term basis. They should not be used for symptomatic relief, or as a replacement for alternative prophylactic therapy. Long-acting β2-agonists should be used with caution in those given slow release β2-agonist tablets. Salmeterol is administered by inhalation and has a slow onset of action but bronchoconstriction is relieved for up to 12 hours. It can be used in children over 4 years, but the long-term effects have not been fully documented. Formoterol is administered by inhalation and has a rapid onset of action, comparable to that of the short-acting β2-agonists, and a duration of action of approximately 12 hours. Bambuterol is a pro-drug of the short acting β2-agonist terbutaline. It is taken orally and has a sustained bronchodilator effect, lasting up to 24 hours. It is not recommended in children. Indacaterol and olodaterol are inhaled β2-agonists that act within 5 minutes and provide sustained bronchodilation for 24 hours. Vilanterol is an inhaled β2-agonist that acts within 15 minutes; its effects also last up to 24 hours.
All β2-agonists are contraindicated for use with β-blockers, including eye drops. Over usage may result in dose-related increases in pulse rate, physiological tremor, blood glucose concentration and potentially serious hypokalaemia.
Xanthines are indicated as adjuncts to maximal anti-inflammatory treatment and short-acting β2-agonists PRN. Patients with severe asthma receiving high doses of these drugs should have serum potassium levels measured as hypokalaemia may be potentiated. Sustained-release preparations are of particular benefit in preventing nocturnal asthma. In children, up to one third will experience GI disturbance, sleep disruption and/or psychological changes. The high incidence of side-effects requires close monitoring to maintain serum levels at 10 to 20 microgram per ml. Clearance of xanthines is increased by smoking and alcohol, but reduced in acute viral infection, cardiac failure and hepatic disease. Clearance can also be affected by a wide range of drugs.
Note: Sustained-release preparations containing the same quantity of xanthine are unlikely to have the same pharmacokinetic profile. It is essential that they are prescribed by brand name and patients are not transferred from one preparation to another without full clinical assessment and retitration.
Regular inhalation of antimuscarinics (anticholinergics) is indicated where control is inadequate with maximal anti-inflammatory treatment and a short-acting β2-agonist PRN. Under specialist guidance, ipratropium can be of use for symptom relief during the first year of life when short-acting β2-agonists may be ineffective. Antimuscarinics are of value in the treatment of chronic obstructive pulmonary disease (COPD) since vagal cholinergic tone appears to be the only reversible component of airway narrowing. They have a slow onset but a prolonged duration of action, with ipratropium lasting up to 8 hours, aclidinium up to 12 hours and glycopyrronium, tiotropium and umeclidinium up to 24 hours. Aclidinium, glycopyrronium, tiotropium and umeclidinium are indicated for the maintenance treatment of COPD. Side-effects are uncommon, but caution should be exercised in patients with glaucoma and prostatic hypertrophy and in children where sputum viscosity may be increased.
Corticosteroids prevent attacks by reducing airway hyper-responsiveness and bronchial mucosal inflammatory reactions such as oedema and mucous secretion.
Inhaled steroids are the mainstay of prophylactic therapy. They are the recommended preventer drugs for adults and children for achieving overall treatment goals. They should be prescribed for patients using inhaled β2-agonists three times a week or more; those who are symptomatic three times a week or more; and those who wake one night a week. Inhaled steroids should also be considered for patients who have had an asthma attack requiring oral corticosteroids in the last two years. Relatively small doses of inhaled steroids may be effective although an increase in dosage may be used temporarily to achieve stability. Therapy should be reviewed regularly and titrated down to the lowest effective dose to control symptoms. Persisting symptoms, despite good inhaler technique, suggest the need for higher or more frequent doses. If a child's asthma is not controlled on the maximum licensed dose, refer child to a specialist in paediatric asthma. Using a medium or large volume spacer in conjunction with an MDI will enhance lung deposition and reduce oropharyngeal deposition. Absorption can also be minimised by rinsing the mouth after inhalation of high dose steroids. Side-effects with inhaled steroids are uncommon; minor local effects become evident at higher doses. However, children's growth should be regularly monitored and the possibility of adrenal insufficiency should be considered, particularly if presenting with reduced level of consciousness.
Note: Not all inhaled steroid doses are clinically equivalent and care should be taken when transferring therapies.
Oral steroids can be used for short course rescue therapy in the control of asthma exacerbations with few side-effects. Also, where control of symptoms cannot be achieved with maximal doses of inhaled steroids and bronchodilators the addition of steroid tablets may be used to prevent severe attacks. In young severe asthmatics, low alternate day dosing under specialist guidance may be of use. Suppression of the hypothalamic pituitary-adrenal axis is possible although systemic side-effects are more frequent with prolonged use and at high doses. Regular assessment of response is therefore essential to facilitate dose reduction. Oral and injectable corticosteroids for use in asthma can be found in the inflammatory disorders section of the Endocrine chapter.
The leukotriene receptor antagonist montelukast is used as oral add-on therapy in mild to moderate asthma inadequately controlled by inhaled corticosteroids and short-acting β2-agonists.
The PDE4 inhibitor roflumilast is licensed as an add-on to bronchodilator therapy for severe COPD associated with chronic bronchitis and frequent exacerbations. It acts as an anti-inflammatory.
Non-steroidal anti-inflammatories are indicated in adults who require bronchodilatation more than once daily or who have nocturnal symptoms and where steroid therapy is inappropriate. Side-effects are extremely rare.
Omalizumab is an anti-IgE antibody administered by subcutaneous injection and is used as add-on therapy to improve asthma control in patients with severe persistent allergic IgE-mediated asthma who have a positive skin test to a perennial aeroallergen. The anti-IL-5 antibodies mepolizumab and reslizumab and the anti-IL-5-receptor antibody benralizumab are indicated as add-on therapy in severe refractory eosinophilic asthma.