Inhibit mast cell degranulation: act on β2-adrenergic receptors on mast cells. This interaction increases intracellular cAMP levels. The elevated cAMP levels activate the cAMP-PKA signaling pathway, suppressing IgE/antigen-dependent signaling and reducing calcium influx, which is essential for degranulation. Related to using epinephrine on anaphylaxis.
Types
Long-acting beta-2 agonists (eg, salmeterol, formoterol) are typically used for maintenance therapy in COPD or with inhaled corticosteroids in asthma. These drugs have a lipophilic side chain, which allows them to attach to the plasma membrane and diffuse laterally across to the beta-2 receptor. As a result, they have an extended duration of action (≥12 hours) but slow onset of action.Salmeterol has a slightly longer duration of action than formoterol due to its ability to bind a secondary exosite within the beta-2 receptor, which serves as an anchor to prevent active site dissociation.
Short-acting beta-2 agonists (eg, albuterol, levalbuterol) are typically used for acute symptom relief. These drugs are relatively hydrophilic, interact minimally with the plasma membrane, and are rapidly metabolized, explaining their rapid onset (minutes) and short duration of action (4-6 hours)
Adverse effects
Tremor: Due to β2 receptor stimulation in skeletal muscle.
Tachycardia/Palpitations: Due to some β1 cross-reactivity or reflex tachycardia from vasodilation.
Hypokalemia: Due to β2 receptor stimulation of the Na+/K+ ATPase, which drives K+ intracellularly.
Hyperglycemia: Due to ↑ hepatic gluconeogenesis and glycogenolysis.
Headache, nervousness.
Tachyphylaxis: Tolerance can develop with frequent use.