Inhalation Therapy for Airway Disease
Patricia M. Dowling, DVM, MS,
The latest approach to the management of inflammatory airway disease is inhalation therapy using metered dose inhalers (MDIs). With inhalation therapy, high drug concentrations are delivered directly to the lungs and systemic side effects are avoided or minimized. The onset of action for inhaled bronchodilators and anti-inflammatory drugs is substantially shorter than for oral or parenteral formulations. Nebulizers have been used for a long time in veterinary patients, but the overall efficiency of drug delivery is low, and the equipment is cumbersome and inconvenient for owners. Administration of medications with an MDI is now commonplace in the treatment of feline asthma.
Human MDIs are designed for actuation during a slow, deep inhalation for optimal lung delivery. This is obviously impossible to control in animals. The addition of a spacer enables the MD1 to be used in small animals. Spacers decrease the amount of drug deposited in the oropharynx (up to 80% of the actuated dose with the MDI alone), thereby substantially reducing systemic drug absorption and other potential side effects, such as yeast overgrowth (thrush), coughing, and dysphonia.
The drugs currently available in MDI formulations include beta, agonists, glucocorticoids, ipratropium bromide, cromolyn sodium, and nedocromil. Each product delivers a set amount of drug- per actuation (puff). In the United States, MDIs are labeled according to the amount of drug delivered at the mouthpiece, whereas in Canada and the European Union, they are labeled according to the amount of drug delivered from the valve. The U.S. system is used here.
For client convenience, MDIs are color coded to aid identification. (For a pictorial guide to MDls, see http://maxshouse.com/feline_asthma_and_bronchitis.htm.) Even in human medicine, the relative potencies, risks of adverse effects, and optimal dose of the different inhaled asthma medications are still unclear. The results of clinical use in asthmatic cats and dogs with chronic bronchitis have been promising but anecdotal, and clinical trials are needed to determine the most efficacious therapies.
Albuterol is available in the United States under the trade names Ventolin (GlaxoSmithKIine, Research Triangle Park, North Carolina) and Proventil (Schering Corp., Kenilworth, New Jersey). it is marketed as salbutamol in Canada and the European Union. Albuterol is a short-acting beta2 agonist that is the medication of choice for treating acute exacerbations of bronchoconstriction. It relaxes smooth muscle and increases airflow within 5 minutes of administration. Albuterol's effects last 3 to 6 hours. Although effective for symptomatic relief of bronchoconstriction, albuterol does not control inflammation. Monotherapy may exacerbate airway disease and increases morbidity and mortality in human asthmatics. Tolerance may develop with chronic therapy from down-regulation of beta, receptors. The Proventil MDI is dark blue, and the Proventil MDT is light orange. Each actuation delivers 90µg of albuterol.
Salmeterol (Serevent [GlaxoSmith Kline]) is a long-acting beta2 agonist. Its onset of action is slow (15 to 30 minutes), but its duration of action is long (over 12 hours). It is not recommended for use in acute bronchoconstriction, but it improves symptom control when used daily in addition to glucocorticoids, more than would simply increasing the glucocorticoid dose. The salmeterol MDT is green, and each actuation delivers 21 µg.
Inhaled glucocorticoids are the most potent inhaled antiinflammatory drugs currently available. In human beings, early intervention with inhaled glucocorticoids improves asthma control and normalizes lung function and may prevent irreversible airway damage. Improvement after inhaled administration of glucocorticoids can occur within 24 hours of beginning treatment, although maximum benefit may not be achieved for I to 2 weeks or longer after starting treatment. When glucocorticoids are discontinued, asthma stability may persist for several days or longer. The potential risk of adverse side effects of glucocorticoids is well balanced by their efficacy in chronic management of inflammation. Oral candidiasis (thrush), dysphonia, and reflex cough and bronchospasm are the most common adverse effects in humans; all of these effects are reduced by the use of a spacer. The risks of systemic side effects, such as suppression of the hypothalamic-pituitary axis, are less than with oral prednisone or prednisolone therapy inhaled glucocorticoid formulations include fluticasone (Flovent [GIaxoSmithKIine])-1 beclomethasone (Beclovent [GlaxoSmithK]ine] and Vanceril [Schering Corp.]),budesonide (Pulmicort [AstraZeneca, Wilmington, Delaware]); and Proventil [Schering Corp.]),- and triamcinolone (Azmacort [Aventis Pharmaceuticals, Bridgewater, New Jersey]). Currently, fluticasone is considered the most potent glucocorticoid formulation with the longest duration of action. Because of its large molecular size, systemic absorption is minimal. Fluticasone MDIs are orange. Fluticasone is available in three sizes; each actuation delivers 44, 110, or 220 µg.
Ipratropium bromide (Atrovent [Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut]) is a quaternary derivative of atropine that lacks its adverse side effects. In asthmatic humans, ipratropium bromide is used as an additional reliever medication to reverse bronchoconstriction when inhaled short-acting beta2 agonists do not give enough relief Its anticholinergic action also decreases mucous secretions. In an experimental model of feline asthma, longterm antigen sensitization caused an augmented muscarinic receptor response to acetylcholine. Modulation of muscarinic receptors with anticholinergic drugs may be useful for treatment of asthmatic cats. Currently, there are no published reports of the use of ipratropium in the cat; however the drug has shown efficacy in horses. It is not well absorbed after inhalation and therefore does not cause systemic cholinergic effects. The Atrovent MDT is encased in a clear holder with a white mouthpiece and green cap; it delivers 18 µg per actuation.
MAST CELL STABILIZERS
Because of the sensitivity of the cat to serotonin released from degranulating mast cells, these drugs should be further investigated in asthmatic cats. The cromolyn MDI is white and delivers 800 µg per actuation. The neclocromil MDT is also white and delivers 1.75 mg per actuation.
Human MDls (OptiChamber [Respironics HealthScan Asthma and Allergy Products, Cedar Grove, New Jersey] and Aerochamber [Forest Pharmaceuticals]) may be modified for use in dogs and cats. Also, recently a small animal-specific spacer has become available (AcroKat [Trudell Medical International, London, Ontario, Canada]). The OptiChamber must be modified with a suitable face mask, such as the type used to "mask" cats for anesthesia. The Aerochamber is available with a variety of face masks intended for infants, children, and adults that will conform to a variety of veterinary patients. The Aerochamber is color coded according to the type of face mask (orange for infants, yellow for children, blue for adults). Both the OptiChamber and the Aerochamber are equipped with one-way valve leaflets that allow the owner to actuate the inhaler away from the cat or dog and then apply the spacer. The AeroKat spacer is valveless, therefore actuation must occur with the mask applied. The device fits cats and most small dogs. Human spacers can be purchased at most pharmacies.
TECHNIQUE FOR USING MDIs AND SPACERS IN DOGS AND CATS
No Note: When a beta2 agonist is used in conjunction with a glucocorticoid or anticholinergic drug, it should be administered 5 minutes before the glucocorticoid or anticholinergic drug. The resulting bronchodilation results in increased deposition of the glucocorticoid or anticholinergic drug in the smaller airways.
The steps for using the MDI are as follows:
Prime the MDI prior to first use or if it has not been used recently, because the initial actuation contains higher drug concentrations than subsequent actuations.
Immediately before each use, shake the inhaler.
Keep track of the number of actuations administered. Some manufacturers include a "check off" list in the patient directions. For daily maintenance medications, divide the number of actuations per canister (printed on the canister) by the number of puffs to be taken each day to calculate how many days the device will last and when the MDT should be replaced. The widely used method of immersing the inhaler in water to see if it floats is inaccurate. Discard the canister after the labeled number of actuations.
SUGGESTED TREATMENT REGIMENS
For emergency management of dyspnea, two to four puffs of albuterol should be given every 20 minutes until clinical signs resolve. Additional therapy may include oxygen administration and an intravenous dose of a rapid-acting glucocorticoid.
Feline Asthma and Chronic Conine Bronchitis
The current recommended chronic therapy for feline asthma and chronic canine bronchitis is salmeterol, the long-acting bronchodilator, at a dosage of one puff (21 pg) twice a day and 220 pg of fluticasone twice a day. For initial therapy of moderately affected animals, a 5-day course of oral prednisone (I mg/kg) may be helpful. Severely affected animals may require I mg/kg of prednisone every other day, Adjunctive therapy with ipratropiurn or nedocromil or cromolyn may be useful in some patients. Therapy must be individualized for the patient.
See: Feline Asthma and Chronic Conine Bronchitis
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