Article #2 CE An In-Depth Look: FELINE BRONCHIAL ASTHMA Feline Bronchial Asthma: Treatment* Christopher G. Byers, DVM VCA Veterinary Referral Associates, Inc. Gaithersburg,MD Nishi Dhupa, BVM, MRCVS, DACVECC, DACVIM Cornell University ABSTRACT: Treatment of feline bronchial asthma is directed toward promoting bron- chodilation, reducing inflammation, and restoring normal mucus clearance. Therefore, determining and subsequently eliminating the inciting cause(s) of feline bronchial asthma should be the therapeutic priority of veterinary practitioners. Emergency treatment, including supplemental oxygen ther- apy, glucocorticoids, β2-adrenergic agonists, and methylxanthines, is often indicated. Long-term therapy is aimed at further reducing inflam- matory cell infiltration into the tracheobronchial tree and may be accom- plished with inhalant glucocorticoids and antileukotriene medications. eline bronchial asthma is a reversible respiratory condition of the lower airways char- acterized by altered airway immunosensitivity. Many medications, including β2- Fadrenergic agonists and glucocorticoids, are available for treating acute and chronic feline bronchial asthma (see boxes on page 427; Table 1). In addition, novel therapies, most notably adjuvant magnesium and leukotriene modifiers, are currently being *A companion article on intensely investigated as therapeutic adjuncts in managing feline bronchial asthma. pathophysiology and diagnosis appears on page 418. β2-ADRENERGIC AGONISTS β2-adrenergic agonists are used extensively in treating acute asthmatic patients in Send comments/questions via email veterinary and human medicine; these drugs are the rapid stimulators of β2-adrenergic [email protected] receptors, producing almost immediate relaxation of airway smooth muscle.1–3 or fax 800-556-3288. Albuterol sulfate and terbutaline sulfate are oral β2-adrenergic agonists used in veteri- Visit CompendiumVet.com for nary medicine for their speedy and beneficial effects, including bronchodilation, inhibi- full-text articles, CE testing, and CE tion of acetylcholine release, stabilization of mast cell membranes, reduction of vascular test answers. permeability, and promotion of mucociliary clearance.3 Terbutaline sulfate is also avail- COMPENDIUM 426 June 2005 Treatment CE 427 Drugs Contraindicated for Treatment Protocols for Cats with Acute 2,6 Use with β2-Adrenergic Agonists in Bronchial Asthma Treating Feline Bronchial Asthma Intermittent clinical signs Sympathomimetic amines • Albuterol sulfate inhaler (108 µg as needed) • Isoproterenol (Isuprel, Sanofi Winthrop) • Epinephrine (AmVet Epinephrine 1:1,000, Neogen) Mild to moderate clinical signs • Dopamine (Intropin, Faulding) • Supplemental oxygen therapy • Dobutamine (Dobutrex, Lilly) • Albuterol sulfate inhaler (108 µg as needed) or terbutaline sulfate (0.325–0.625 mg [total dose/cat] Tricyclic antidepressants PO bid or tid) • Imipramine hydrochloride (Tofranil, Novartis) • Theophylline extended release (25 mg/kg PO in the • Imipramine pamoate (Tofranil-PM, Novartis) evening) or aminophylline (6.6 mg/kg PO bid) • Amitriptyline (Elavil, Zeneca) • Prednisolone (1 mg/kg PO bid for 5 days, then 1 • Clomipramine (Clomicalm, Novartis) mg/kg PO sid for 5 days, then 1 mg/kg PO every • Doxepin (Sinequan, Roerig) other day for 5 days) • Fluticasone propionate inhaler (110–220 µg bid) Monoamine oxidase inhibitors • Selegiline hydrochloride (Anipryl, Pfizer) Initial treatment for severe clinical signs • Supplemental oxygen therapy • Albuterol sulfate inhaler (108 µg q30–60min until respiratory distress resolves) or terbutaline sulfate able as an injectable medication and may be adminis- (0.01 mg/kg SC or IM up to q4h) tered subcutaneously or intramuscularly. Administration • Dexamethasone sodium phosphate (1 mg/kg IV of these medications is contraindicated if a patient is or IM) receiving concurrent sympathomimetic amines, tricyclic • Consider adjuvant magnesium administration antidepressants, or monoamine oxidase inhibitors be- After stabilization cause these medications may perpetuate various cardiac • Prednisolone (1 mg/kg PO bid for 5 days, then 1 dysrhythmias (see box on this page). Furthermore, mg/kg PO sid for 5 days, then 1 mg/kg PO every administration of β2-adrenergic agonists should be other day for 5 days) avoided in patients being treated for cardiac disease • Fluticasone propionate inhaler (220 µg bid; wean to lowest possible dose) because these medications have a minimal effect on β1 4 • Albuterol sulfate inhaler (108 µg as needed) receptors in the heart. Stimulation of cardiac β1 recep- tors may evoke tachyarrhythmias; thus all patients receiv- ing β2-adrenergic agonists should be closely monitored for evidence of tachycardia, tremors, central nervous sys- ing the rate of cAMP degradation.3 Methylxanthines tem (CNS) excitement, hypertension, vomiting, mydria- should be cautiously administered to patients with car- sis, and dizziness.4 diac disease because these medications have inotropic and chronotropic effects.4 Tachyarrhythmia may also METHYLXANTHINES develop following methylxanthine administration. These Human and veterinary pharmacology studies have medications also increase gastric acid secretion, and signs demonstrated that methylxanthines inhibit phosphodi- of nausea and vomiting may manifest. Other potential esterase—the enzyme responsible for cAMP degra- signs of methylxanthine intoxication are the results dation.5,6 This class of bronchodilators is the most widely of profound CNS excitation, including nervousness, used and studied in cats with acute asthma, and although excitability, tremors, ataxia, and/or seizures. Both non- the effects of the drugs are rapid, the mechanism of sustained and sustained release products are available for action in feline bronchial asthma remains unclear be- prescription. The bioavailability of orally administered cause methylxanthines do not inhibit phosphodiesterase nonsustained release products is reportedly 100%, at therapeutic levels.3,7,8 Aminophylline and theophylline whereas that of sustained-release products is significantly promote swift bronchodilation, stabilize mast cells, lower.4–7 However, the duration of effect of the sus- increase frequency of ciliary beating, and enhance tained-release medications is longer, allowing lower diaphragmatic contractile strength, possibly by depress- doses and/or reduced dosing frequencies. June 2005 COMPENDIUM 428 CE An In-Depth Look: Feline Bronchial Asthma Table 1. Drugs Commonly Used in Treating Feline Bronchial Asthma4 Drug Brand, Manufacturer Dose Terbutaline sulfate Brethine, Geigy 0.312–0.625 mg (total dose/cat) PO q24h Albuterol sulfate Proventil, Schering 108 µg inhaled as needed Prednisolone Prelone, Muro 1–2 mg/kg/day PO Theophylline extended release Slo-bid, Rhône-Poulenc Rorer 25 mg/kg PO q24h in the evening Theophylline Theolair, 3M Pharmaceuticals 6–8 mg/kg PO bid Fluticasone propionate Flovent, GlaxoSmithKline 44–220 µg inhaled bid Zafirlukast Accolate, AstraZeneca 1–2 mg/kg PO q24h bid Montelukast sodium Singulair, Merck 0.25–0.50 mg/kg/day PO Dexamethasone sodium phosphate Dexaject SP, Vetus 1 mg/kg IV Cyproheptadine hydrochloride Periactin, Merck 1–2 mg PO bid GLUCOCORTICOIDS treating cats with bronchial asthma are prednisolone Glucocorticoids are essential in treating bronchial and prednisone. Prednisone is reduced in the liver via asthma patients in critical condition. These drugs bind glutathione metabolism to form the active hydroxyl to cytosolic receptors, and the glucocorticoid-receptor form—prednisolone; a relatively recent study docu- complexes move to an intranuclear position to alter gene mented reduced glutathione levels in both dogs and cats transcription. Specifically, glucocorticoids are thought to with naturally occurring liver disease.10,11 Thus cats sus- inhibit transcription of proinflammatory mediators, pected of having any level of glutathione depletion most notably interleukin (IL)-5, released in cats with and/or significant underlying hepatic disease may bene- bronchial asthma. These drugs also markedly reduce the fit more from prednisolone therapy. The effects of number of macrophages, lymphocytes, neutrophils, chronic, oral steroid treatment in cats may include eosinophils, and mast cells involved in airway inflamma- insulin resistance, polyuria, cystitis, and inappropriate Acute therapeutic intervention for feline bronchial asthma may involve administration of β2-adrenergic agonists, glucocorticoids, methylxanthines, and magnesium therapy. tion because they decrease the rate of inflammatory cell urination. Therefore, inhaled steroids that do not cause diapedesis and migration, promote apoptosis of these profound systemic effects are gaining popularity. cells, and decrease mucus production. The results of one Glucocorticoids and bronchodilators may be given human study documented that glucocorticoids indirectly effectively by inhalation to cats experiencing acute augment bronchodilation by increasing the number of episodes of bronchial asthma; each class of drug is avail- 12 β2-adrenergic receptors and acting synergistically with able as a metered-dose inhaler (see boxes on page 429). 9 methylxanthines. Glucocorticoids do not have an onset Albuterol sulfate is a β2-adrenergic agonist used as a of action as rapid as β2-adrenergic agonists and/or metered-dose aerosol medication. Fluticasone propionate methylxanthines; thus the benefits of altered gene tran- and beclomethasone dipropionate are more common scription and reduced cellular