Mode of Action
LABA are highly specific for β2 adrenoceptors and have a prolonged duration of action of 12 hours. Both formoterol and salmeterol remain in tissue despite antagonism and extensive perfusion. LABA are very potent at low concentrations, thus reducing stimulation of β2 receptors in non-pulmonary tissue.
Salmeterol is a partial agonist (approximately 70% agonist activity compared to isoprenaline), while formoterol is a full agonist of β2 receptors. The implications of this finding for disease control are unclear. Cardiac and metabolic effects of formoterol are comparable to those of salbutamol, but formoterol has a rapid onset (2-3 minutes) of bronchodilator action, while salmeterol activity commences at 10 minutes and reaches a maximal effect at about 30 minutes. Both formoterol and salmeterol provide dose responsive bronchodilatation.
While LABA appear to have minimal effects on in vivo airway inflammation, they enhance the effect of inhaled corticosteroids via different mechanisms. They improve glucocorticoid receptor availability and synergistically suppress inflammatory mediator release. Corticosteroids in turn improve β2 receptor expression and prevent receptor down regulation.
Side effects occur in a dose-dependent manner and include:
- Fine tremor,
- Tachycardia and palpitations,
- Pupil dilatation and
LABA should not be used as first line therapy to maintain control or as short term-reliever therapy.
LABA should be reserved for symptomatic patients using a moderate dose of inhaled corticosteroid (>500 mg BDP-HFA or its equivalent daily).
Salmeterol and formoterol are available both in dry powder and aerosol forms.
Clinical trials demonstrate greater efficacy in controlling symptoms, improving peak flow rates and reduction of diurnal variation with the addition of a LABA to moderate doses of ICS in comparison with doubling the ICS dose.
Nocturnal LABA use can ameliorate night-time symptoms and premedication (30 minutes for salmeterol) prior to exercise can reduce exercise-induced bronchoconstriction.
Several randomized double-blind, placebo-controlled clinical trials, primarily with formoterol, demonstrate that adding a LABA to an ICS markedly reduces the rate of severe asthma exacerbations.
LABAs and ICS are now marketed as a combination treatment in the same inhaler (formoterol + budesonide, fluticasone + salmeterol). This formulation improves compliance, since it requires one rather than two prescriptions, and reduces costs, in that the combination devices are usually cheaper than two individual components alone. The formoterol/budesonide combination has been suggested as single inhaler therapy for both maintenance and reliever therapy.