Corticosteroids are the most potent drugs currently available for the treatment of heaves (Table Medications Recommended for the Treatment of Heaves). The mechanisms of action of corticosteroids include decreasing smooth muscle contraction and epithelial damage by inhibiting the effects of inflammatory cells and their mediators, potentiation of the bronchodilating effects of catecholamines and reduction of mucus production. Corticosteroids with potent antiinflammatory effects are also more likely to result in detrimental effects. Corticosteroids have been commonly administered systemically, and more recently, by inhalation. An advantage of inhaled medication is achievement of a high local concentration of drug in the lungs while minimizing systemic effects. A number of corticosteroid drugs have been proposed for the treatment of heaves but objective information concerning their comparative efficacy and toxicity is sparse. Drug selection depends on the severity of the clinical signs and the ability to improve the environment. The minimal effective dose should be used, and the prolonged systemic administration of corticosteroids usually is avoided to prevent side effects.
Systemic corticosteroid administration for a minimum of 2 weeks usually is recommended for the control of heaves. A delay of a week can be expected between the initiation of therapy and the maximal clinical response, although some improvement may be observed within a few days of drug administration. Therefore in horses with severe respiratory dysfunction, corticosteroids should be combined with drugs such as bronchodilators, which can provide symptomatic relief more rapidly. If concurrent environmental control is not performed, the respiratory signs are likely to recur soon after cessation of drug administration. For a severe attack, dexamethasone (initial dose 0.05-0.1 mg/kg, IV, followed by decremental doses and alternate day dosing) has proven efficacious to control clinical signs.
Isoflupredone acetate has the advantage that it can be administered by the intramuscular route and is as effective as dexamethasone in improving the airway function of horses with heaves. The dose used is 10 to 14 mg intramuscularly daily for 5 days; the drug is then administered on alternate days and tapered to a low dose over a period of 10 to 20 days. Although hypokalemia may occur after the administration of isoflupredone acetate to horses, the severe hypokalemic myopathy reported in cattle and in people apparently does not occur when this drug is used in horses.
Triamcinolone acetonide (20-40 mg IM) also reverses clinical signs of airway obstruction in horses with severely impaired airway function. Because long-acting corticosteroids are more likely to be associated with detrimental side effects, triamcinolone administration is recommended when short-acting corticosteroids cannot be administered. Even in severe cases when no improvement has been made in the horse’s environment, the clinical improvement lasts up to 5 weeks.
Prednisone and prednisolone are less potent and less toxic than the above corticosteroids and have been used for the treatment of mildly affected horses. Recent studies have shown that oral prednisone is absorbed poorly in horses and, when administered in conjunction with environmental changes, provides no additional benefit over management alone.
Inhalation therapy is well-suited to corticosteroid administration because of the large number of glucocorticoid receptors at the level of bronchial epithelial cells and vascular endothelial cells. Inhalation therapy allows a maximal concentration of drug at the effector sites and minimizes side effects. Inhaled corticosteroids may therefore be preferable when prolonged therapy would be required.
Beclomethasone dipropionate (BDP) in metered-dose inhalers (MDIs) improves respiratory mechanics parameters within 3 to 4 treatment days. The maximal beneficial effects usually are observed during the first week of therapy. Fluticasone propionate (FDP) administered from a MDI and a mask also results in a decrease in airway obstruction, in neutrophil counts, in bronchoalveolar lavage fluid, and in bronchial hyperresponsiveness.
The information available to date in horses suggests that the short-term administration of inhaled corticosteroids is both efficacious and well tolerated but has little residual effect when the treatment is discontinued. Because a delay in response is expected with inhaled corticosteroids, they should be combined with faster acting drugs, such as bronchodilators or systemic corticosteroids in horses with respiratory distress. Bronchodilator administration also may improve pulmonary distribution of aerosolized surface-active antiinflammatory preparations. Masks used in combination with MDIs or dry powder inhalers (DPIs) increase the resistance to airflow and therefore may not be suitable and well tolerated for the initial treatment of horses with labored breathing. This author has treated a few horses that became reluctant to inhale the medication after a few days. Replacing the poorly tolerated drug with another of the same class often corrects this problem.
Chronic airway inflammation in heaves results in airway remodeling. The dosages and duration of corticosteroid administration required to restore the normal lung morphology in heaves are unknown but are likely to exceed, by far, the usually recommended posology.
Side effects of corticosteroids are uncommon based on the available literature. Detrimental findings that have been reported after systemic corticosteroid administration to heaves-affected horses include laminitis, suppression of the hypothalamo-pituitary-adrenal axis, altered bone metabolism, and bacterial pneumonia. To date, the only side effect attributed to inhaled corticosteroids is a decrease in serum cortisol.