Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 3

(a)

(b) (c)

(d)

FIGURE 1.1 Examples of structures of common pharmacological agents used in medical and pharmaceuti-
cal aerosols for delivery to the lungs (space-illing models of (a) salmeterol, (b) luticasone, (c) ipratropium,
and (d) cromolyn).

agents fell into three groups: catechols, resorcinols, and saligenins. 16 Each compound was a struc-
tural analog to epinephrine (adrenaline). Indeed, epinephrine appeared in an early product, which
is now available over the counter at pharmacies (Primatene, Whitehall-Robins, Richmond, VA).
After some early toxicity issues with nonspeciic β-adrenergic agonists, the speciic β 2 -adrenergic
agonists were produced and introduced with great success to manage the symptoms of asthma.
The irst pharmacologically speciic product, albuterol (GSK, RTP, NC), was a short-acting agent
introduced in the 1960s. It was followed by a number of variants including fenoterol (BI, Ingelheim,
Germany) and terbutaline (Astra-Zeneca, Lund, Sweden). In the late 1980s and early 1990s, these
were replaced for routine maintenance therapy by long-acting β 2 -adrenergic agonists, notably for-
moterol (BI, Ingelheim, Germany) and salmeterol (GSK, RTP, NC). The short-acting agents were
retained as rescue medications for patients experiencing acute exacerbations. The newest treatment
options being investigated allow for a single daily dose and fall under the class of ultra-long-acting
β 2 -adrenergic agonists (ultra-LABAs). Indacaterol has been approved for usage in Europe (Onbrez,
Novartis, Basel, Switzerland), and the other products currently in the most advanced stages of devel-
opment are carmoterol and GSK-642444 (GSK, RTP, NC). 17