Antiasthmatics – Serevent
Another asthma drug, salmeterol xinafoate, works through a different mode of action from that of Flonase. GlaxoSmithKline has marketed salmeterol xinafoate with the trade name Serevent since 1990. A highly lipophilic drug, Serevent rapidly crosses the bronchial epithelium and is retained in the lung surface. It has a slow onset with prolonged duration of action and is virtually resistant to washout.
Serevent is a beta-adrenoceptor agonist. It works by dilating the lung’s bronchial tubes, which become constricted and make it difficult for asthmatics to breathe. Believe it or not, beta-adrenoceptor agonists, one of the oldest classes used in medicine, have been known for more than 5,000 years to relieve bronchoconstriction by mimicking the effect of adrenaline.
As early as 3000 B.C., the Chinese used sympathomimetic agents to relieve breathing difficulties. The active principle, an alkaloid now identified as ephedrine, was originally extracted from the plant Ephedra equisetina and known as Ma Huang. However, Ma Huang was not introduced into Western medicine until 1924. In 1948, Raymond P. Ahlquist at the Medical College of Georgia speculated that there were two types of adrenergic receptors (adrenoceptors for short), which he termed alpha-adrenoceptor and beta-adrenoceptor. Whereas beta-blockers are excellent drugs for lowering blood pressure, beta-adrenergic agonists are the most prescribed class of drugs for the treatment of asthma. Beta-adrenergic agonists are preferred both for the rapid relief of symptoms and for the level of bronchodilation achieved in patients with bronchial asthma. They have now become standard bronchodilators in emergency rooms and in day-today use as reliever medicine to help the patient breath.
These drugs produce their effects through stimulation of specific (З2-adrenergic receptors located in the plasma membrane, resulting in alterations in adenylyl cyclase and elevations in intracellular AMP. Long-acting (З2-adrenergic agonists, such as salmeterol xinafoate (Serevent), are very lipophilic and have a high affinity for the receptor by a different mechanism. However, these treatments also suffer from a variety of side effects. The widespread distribution of (З2-adrenergic receptors results in a number of undesired responses when these agents are absorbed into the systemic circulation. Tremor is the most common side effect and results from stimulation of the (32-receptor in skeletal muscle. The most serious side effects are cardiac in nature (increased heart rate, tachyarrhythmias) that result from stimulation of the (32-receptor in the heart. Most of these side effects disappear with long-term use and do not have any long-term health consequences.
GlaxoSmithKline combined two asthma drugs with different mechanisms and arrived at Advir, which is composed of Serevent (a beta-adrenergic agonist) and Flonase (a glucocorticoid). In 2004, Advir became very successful in controlling asthma and brought in $4.5 billion in annual sales for GlaxoSmithKline. It was the company’s best-selling drug. In addition, formoterol (Foradil), marketed by Novartis and Schering-Plough, is another (3-adrenergic agonist for asthma. In August 2003, the FDA added a black-box warning on Serevent and Advir, stating that they possess «small but significant increased risk of life-threatening asthma attacks or asthma-related deaths seen in patients taking salmeterol in a recently completed U.S. study.» However, in July 2005, a panel of experts for the FDA evaluated the risk versus benefit of these drugs and recommended that Foradil, Serevent, and Advir be kept on the market.
