Clenbuterol, a beta-2-adrenoceptor agonist and the only FDA-approved medication for horses with reversible bronchospasm, is commonly used to treat horses with inflammatory airway disease (IAD) and recurrent airway obstruction (RAO, commonly known as heaves). Although it is often regularly administered to racehorses throughout the racing season, the long-term effects of the drug remained unclear.
To that end, a team of researchers at University of Pennsylvania School of Veterinary Medicine's (PennVet) New Bolton Center carried out a study on the topic and found that while clenbuterol initially reduces airway sensitivity to inhaled histamines, long-term use can result in reduced bronchoprotective effectiveness.
"Many horses, especially race horses, receive clenbuterol every day," explained Rose Nolen-Walston, DVM, assistant professor in the Department of Clinical Sciences at PennVet.
Using a cross-over design, eight retired Thoroughbred racehorses with IAD were treated over a three-week period with either clenbuterol or a placebo. A baseline measurement for airway reactivity was assessed initially, followed by subsequent measurements every seven days.
At the outset of study, clenbuterol effectively reduced airway sensitivity to inhaled histamine; however, by day 14, subjects showed a decreased response to the drug. Likewise, in studies in humans and other mammals, chronic treatment with beta-2-adrenoceptor agonists has resulted in an increased tolerance toward the medication.
Sweat function was also evaluated in this study, as in horses the sweat gland activity is mediated by beta-2 receptors. Clenbuterol tolerance could plausibly result in reduced sweating in response to exercise or excitement, however, horses treated with clenbuterol showed a normal sweat response to epinephrine administration throughout the study period.
"Our study shows that after about two weeks of use, it quits working and actually makes the horses breathe a little bit worse," Nolen-Walston explained. "The clinical significance is that clenbuterol should be used for no more than 14 days consecutively without a break. In humans, the loss of effectiveness can also be prevented by co-administration of corticosteroids, but this has not been investigated in horses."
Further clenbuterol research is called for, Nolen-Walston said. "There are two common reasons that people give clenbuterol: to prevent bronchoconstriction if a horse has IAD, and to improve mucociliary clearance, where the ciliated cells clear the inhaled debris from the lungs," she said. "Clenbuterol speeds mucocilary clearance, so our question is if long-term use of clenbuterol also results in tolerance to this effect, which would be another reason to restrict its use to a maximum of 14 days."
This study, "Effect of prolonged administration of clenbuterol on airway reactivity and sweating in horses with inflammatory airway disease," appeared in a recent issue of the American Journal of Veterinary Research. The abstract is available on Pubmed.
Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.