Asthma is a chronic inflammatory disease of the airways. It is a reversible airway obstruction, occurring 8 to 10% of the population worldwide. According to a study in 2005, asthma affects over 15 million Americans, with more than 2 million annual emergency room visits. Asthma patients have a hyper-responsiveness in their airways and generally and increase in their airway smooth muscle cell mass. This hyperplasia is due to the normal response to the injury and repair to the airway caused by exacerbations. The main choice of therapy for asthma patients is β2- adrenergic agonists. Racemic albuterol has been the drug of choice for a short acting bronchodilator for a long time, but since the development of levalbuterol, there is the question of which drug is a better choice for therapy. Efficacy and cost of treatment must both be taken into consideration in each study of these therapies to determine which is best for the treatment of asthma.
Racemic albuterol is a β2- adrenergic agonist that is a 50:50 mixture of two isomers, (R) albuterol and (S) albuterol. These two isomers are mirror images of each other, and rotate light in opposite directions. (R) Albuterol is an active isomer and in this combination acts an active bronchodilator. The other half of the mixture, (S) albuterol, does not actually possess any bronchodilator activity and was until recently considered an “inactive” distomer or physiologically inert. The “R” stands for rectus or right, while the “S” is for sinister or left. Racemic albuterol was synthesized for maximal airway smooth muscle dilation while minimizing the α- and β1-receptor mediated effects on the cardiovascular system. Levalbuterol is the single (R)-isomer and has a similar structure to epinephrine. It was released in 1999 and was the first of the single isomer available. It does not contain any of the (S) albuterol, so it is entirely focused on the dilation of the airways. (More to come)
Since the isolation of the (R)-isomer for albuterol, quite a few studies have been conducted to differentiate between the effectiveness of each drug, racemic albuterol and levalbuterol, in regards to the treatment of asthma. Studies have looked at how the drugs work in regards to bronchodilation, how long they last in the system, the effects on hospitalization, as well as the cost of treatment with each drug.
Previously, it was believed that (S) albuterol was physiologically inert. It has now been shown to promote the contraction of the airway smooth muscle, the opposite of the desired effect of racemic albuterol. In a study in guinea pigs, (S) albuterol was shown to increase airway hyper-responsiveness, an issue that asthma patients already battle. It was also shown to recruit eosinophils to the airway, increases intracellular calcium and has pro-inflammatory properties. (S) Albuterol stimulates proliferation while (R) albuterol inhibits proliferation. The effects of (S)...