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Shifting Tides of Asthma Treatment–Beta Agonists and the Woody Allen Rule

By Dr. Larry Chiaramonte

Medicine sometimes seems to follow the Woody Allen rule (from the movie “Sleeper”): everything we thought was good for us turns out to be bad, and vice versa. The latest version of this concerns the work of a University of Houston pharmacologist named Richard Bond who received a 2011 Medical Futures Innovation Award (MFIA) in London, the only American to win this year. “[He and his] collaborators have been investigating the once-controversial use of a class of compounds called inverse agonist beta blockers to treat mild, chronic asthma. Their research has shown that while this type of medication triggers an initial short-term negative effect of increased airway constriction, the effect appears to reverse with long-term use…Although inverse agonist beta blocker therapy is not intended to replace ‘rescue’ inhalers for immediately relieving acute asthma attacks, Bond has suggested that a daily dose of the medication he is proposing could prevent or limit the severity or frequency of such attacks.”
Stimulation of beta-receptor sites in the lungs relaxes smooth muscle. The medications that do this [Ventalin, Proventil, Albuterol, Seravent, and Floradil] should be familiar to anyone who manages asthma, and probably most chronic asthma patients. These drugs are called agonists, but for purposes of clarity think of them as protagonists. However, they should only be used in treatment of acute attacks.

On the other side are Beta 2 Receptor antagonists, which down regulate the lung beta-receptor sites. While they may be useful in other conditions, they increase asthma in both the short and long term.

Having Beta2 agonists [protagonists] on one side and evil Beta2 antagonists on the other made life simple. Enter Dr. Bond and the Woody Allen rule: the world of asthma (and probably COPD) has just been made more complicated. Bond has shown that some ?eta blockers, carvedilol and metoprolol, which are used for treating congestive heart failure, result in bronchoconstriction — airway hyper-responsiveness — in the short term, but when taken long term protect against it. These fall under the category Beta inverse agonists. Dr. Bond, by the way, founded a company that holds the patent for one of these drugs, called nadolol.

I think further studies will support the use of Beta 2 -Inverse Agonists in asthma and COPD. The real problem is how to get through the acutely detrimental period to the chronically beneficial one.

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