β -adrenergic agonists

Beta agonists produce bronchodilation by directly stimulating beta₂-receptors in airway smooth muscle, resulting in relaxation. Activation of B₂ receptors results in activation of adenyl cyclase via a stimulatory guanine-nucleotide binding protein [G protein (Gs)] and increases intracellular cyclic 3^’5^’-adenosine monophosphate (cAMP). This activates protein kinase A, which then phosphorylates several target proteins within the cell leading to relaxation.

B₂ agonists act to reverse bronchoconstriction through a direct effect on airway smooth muscle. They have additional effects on airways including inhibition of mast cell mediator release, prevention of microvascular leakage and the development of airway edema, increased mucociliary clearance, increased mucous secretion and decreased cough. The inhibitory effects on mast cell mediator release and microvascular leakage suggests that B2 agonists may modify acute inflammation. B₂ agonists, however, have no effect on chronic inflammation.

B₂ agonists were developed through substitutions in the catcholamine structure of norepinephrine (NE). NE differs from epinephrine in the terminal amine group, and modification at this site confers B receptor selectivity; further substitutions have resulted in B₂ selectivity. The selectivity of B₂ agonists is dose dependent. Inhalation of the drug aids selectivity since it delivers small doses to the airways and minimizes systemic exposure.

These agents can broadly be divided into short and long acting on the basis of duration of action. Short acting agents last for 4-6 hours and long acting for greater than 12 hours. The agents are outlined in Table I

Table 1 – Beta Agonists

Short acting agents

Generic name Brand Name(s) Duration of Action β2-selectivity

Albuterol (racemic) Ventolin, Proventil 4-6 hrs +++

Levalbuterol Xopenex 8 hrs +++

Metaproterenol Metaprel 4-6 hrs ++

Isoproterenol Isuprel 3-4 hrs ++

Epinephrine Primatene Mist 2-3 hrs -

Long acting agents

Generic name Brand Name(s) Duration of Action β2-selectivity

Salmeterol Serevent 12+ hrs +++

Formoterol (none) 12+ hrs +++

Category: Pharmacology Notes