Use of Inhaled Medications to Treat Respiratory Diseases in Dogs and Cats
Noninfectious disorders of the respiratory tract, including laryngitis, tracheitis, bronchitis, and asthma are common problems in dogs and cats. Traditional therapies have often included corticosteroids and bronchodilators given by mouth or injection. Side effects of this form of treatment can be severe and can result in cessation of therapy. Inhaled corticosteroid drugs are not as absorbed into the systemic circulation, do not result in significant side effects, and are now the standard of care for dogs and cats with respiratory diseases that would otherwise be treated with systemic medications.
Introduction
The pulmonary tree is a series of branching tubes that begin at the nose and end within the deep recesses of the lung. The primary function of this system is to bring oxygen from the air into the alveoli of the lungs so that environmental oxygen can be transferred to the bloodstream. “Respiratory disease” is a term used to describe abnormalities anywhere within the pulmonary tree, including the nose, pharynx, larynx, trachea, bronchi, lungs, and chest cavity. When something is wrong within the respiratory system, common signs that are generated include sneezing, reverse sneezing, snorting, wheezing, noisy breathing, nasal discharge, cough, and changes in respiratory rate, depth, and effort. The cause(s) of these respiratory signs range from simple nasal allergies accompanied by sneezing and a clear nasal discharge, to life-threatening asthmatic bronchoconstriction with wheezing.
Many of the common breathing disorders in dogs and cats have a known cause, such as heart failure, bacterial pneumonia, heartworm infection, etc. In these instances, medications are used that are specifically directed at the causes of the respiratory signs (e.g., diuretics, antibiotics, antiparasitical drugs). However, there are a number of common respiratory diseases that do not have recognized specific causes. These conditions include noninfectious rhinitis, laryngeal paralysis, tracheal collapse, chronic bronchitis, and feline asthma.
About the only common denominator that is present in each of these latter pulmonary problems is chronic inflammation. Historically, the most effective treatments for noninfectious airway inflammation have been injectable and oral corticosteroids, such as prednisone and prednisolone.1–3 Many potential systemic side effects can occur from the chronic use of corticosteroids, including behavioral changes, polydipsia, polyuria, increased appetite, skin and urinary tract infections, pancreatitis, and diabetes.4 Fortunately, corticosteroids can now be given by inhalation, and this route minimizes their systemic absorption. This form of drug delivery avoids the complications previously seen with oral and injectable corticosteroids and has become a major advancement in the ability to safely and effectively treat many inflammatory airway diseases in dogs and cats.3
The purposes of this article are to briefly review the disorders that are most likely to respond favorably to inhaled medications, to review the effective drugs available for inhalation administration, and to describe the specific method used to deliver these medications to dogs and cats.
Indications for Inhaled Medications
Chronic rhinitis occurs in both dogs and cats; it is often known as lymphocytic-plasmacytic rhinitis, which reflects the specific inflammatory cells that are found when a biopsy of the affected nasal tissue is performed.5 The resulting inflammation causes sneezing and nasal discharge. The discharge may be clear, but if a secondary bacterial infection is present, the discharge may be green, yellow-green, or gray.
Laryngeal paralysis occurs primarily in dogs, although cats have rarely been diagnosed with this condition.6,7 Laryngeal paralysis adversely affects the ability of the vocal cords and associated cartilaginous structures to open during normal breathing. Although the underlying problem may arise within either the muscular or nervous system, the result is narrowing of the laryngeal opening, which causes airflow to be turbulent. The turbulent airflow induces inflammation and swelling of the vocal cords and cartilages, making the airway even narrower.
Tracheal collapse also appears to be amenable to inhaled medications and is much more common in dogs than in cats.1 Dogs with tracheal collapse often have cartilaginous tracheal rings that are softer than normal and collapse into a “C” shape rather than maintaining a normal, round “O” shape. One result of this deformation is that the short, tight muscle (i.e., dorsal trachealis mm.) that connects the dorsal, open aspect of the tracheal cartilage becomes stretched and prolapses into the lumen of the trachea, causing obstruction. Similar to laryngeal paralysis, the primary obstructive problem is a structural one. When a dog with tracheal collapse coughs, the top and bottom walls of the airway may actually touch, which results in chronic inflammation and stimulation of the cough receptors within the walls of the airway. Inflammation of the cough receptors causes even more coughing, and a vicious cycle of further stimulation of the cough receptors ensues.
Chronic bronchitis has been defined as a daily cough for which other causes of daily coughing (e.g., pneumonia, heart failure, etc.) have been ruled out.8 Both cats and dogs can develop chronic bronchitis. In humans, the number one cause of chronic bronchitis is cigarette smoke. Dogs and cats without exposure to cigarette smoke commonly develop chronic bronchitis, however, so other causes must also exist. Chronic bronchitis is a classic disease of chronic airway inflammation, and endoscopic examination of the walls of the airways reveals inflammatory cell infiltrates, mucosal swelling, and excess mucous production.8
Asthma is a disease that is limited to cats and humans, although horses have a similar condition called “heaves.”9 Asthma has features that are similar to bronchitis, including coughing and excessive mucous production; however, asthma is distinguished by the additional feature of airway smooth-muscle constriction (i.e., bronchoconstriction).10 This additional pathological feature contributes to coughing and wheezing, and in its severest form can cause life-threatening airway closure.
Specific Drugs for Inhalation Use
All of the above disorders have the common feature of chronic airway inflammation. Inhaled corticosteroids control airway inflammation without being absorbed into the systemic vascular bed and, therefore, do not cause systemic and unwanted side effects as do the oral and injectable forms of corticosteroids.11 Additionally, inhaled bronchodilator drugs work more quickly and have fewer side effects than bronchodilator drugs given by other routes [see Table].
Fluticasone Propionate
Fluticasone is a proprietary drug held under patent with the single trade name of “Flovent.”a Three strengths are available (i.e., 44 μg, 110 μg, and 220 μg). Although a number of additional corticosteroid drugs have been produced for inhaled administration, fluticasone is preferred, because it is the most potent and has the longest half-life. Additionally, although several corticosteroids are designed to be inhaled, only about 30% of each drug is actually delivered into the airways. The remaining drug is deposited onto the back of the throat and may be swallowed. This portion of the drug may be systemically absorbed through the gastric mucosa. Fluticasone is the least bioavailable of all the inhaled corticosteroids, and it is absorbed to a lesser degree if exposed to the gastrointestinal tract.
Albuterol Sulfate
Albuterol is a selective beta2-adrenergic bronchodilator. It acts primarily in airway smooth muscle to increase the intracellular concentration of cyclic-3′, 5′-adenosine monophosphate (cyclic AMP).12 An increase in cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in airway smooth-muscle relaxation. This drug is available through different manufacturers and is commonly prescribed as Ventolinb or Proventil.c Because clinically significant airway smooth-muscle contraction (i.e., bronchoconstriction) is relatively uncommon in dogs, the primary use of these drugs is in cases of feline asthma. Albuterol only comes in a single uniform strength (i.e., 90 μg per inhalation).
Delivery Technique
Drugs for inhalation typically come in a rectangular metered dose inhaler (MDI) or a round “diskus” form. At the present time, only the MDI form is practical for use in animals. Recently, the propellants used for these medications have changed. Prior formulations of fluticasone and albuterol were carried by chlorofluorocarbon (CFCs) propellants. Current formulations have replaced the CFCs with tetrafluoroethane (i.e., HFA) propellants to minimize potential adverse effects on the ozone in the environment. This change has not affected the way in which the medications are used or their effectiveness.
The most effective means of using an MDI requires that inhalation be purposefully coordinated with actuation of the device. This coordination cannot be reliably done in most infants, small children, or animals. An alternative method was developed to allow children and animals to use MDIs without the need to coordinate their breathing patterns. In dogs and cats, this method involves the use of a spacer deviced and a mask specifically designed for them [Figure 1]. Small, aerosol-holding chambers are attached to an MDI, an exhalation valve, and a mask. The spacer is approximately the size of the inner cardboard roll used with toilet paper. The MDI fits on one end of the spacer, and the other end of the spacer has an attachment for the face mask. The MDI supplies precise doses of the aerosol drug, and the holding chamber contains the aerosol so it can be inhaled by the cat or dog. The exhalation valve allows for exhaled gases from the animal to go into the atmosphere and not disturb the drug aerosol particles. The mask is designed to cover the nose of the cat and the muzzle of the dog. The designers of these spacers have shown that a holding chamber with a length of 11 cm and a diameter of =3.5 cm delivered almost all of a therapeutically “ideal” aerosol (i.e., aerosol of equivalent aerodynamic diameter =2.8 μm) produced by an MDI, and in some cases delivery was enhanced because of evaporation of large, suspended particles.e
The MDI is first shaken to open an internal valve within the canister, and then it is attached to the spacer. The mask attached to the other end of the spacer is placed snuggly on the animal’s nose or muzzle, and the MDI is pressed to release the medication into the spacer [Figure 2]. The animal is allowed to breathe in for 7 to 10 breaths in order to complete the process. It is important to teach the owner to observe the pet actually breathing, because both dogs and cats may initially hold their breaths when introduced to this form of treatment.
Drug Dosages
When administering fluticasone, it is important to realize that 1 to 2 weeks may be required for the drug to take full effect, and it should be given twice daily. The usual starting dose for cats and dogs <20 kg is 110 μg, which equates to one puff into the spacer q 12 hours. Dogs >20 kg are usually treated with 220 μg of fluticasone. Animals that are currently on oral corticosteroids should be weaned off their oral medication over a 2- to 3-week period once the fluticasone treatment is started. Animals that are newly diagnosed with inflammatory respiratory diseases requiring immediate corticosteroid therapy may be given oral medications at the same time fluticasone is initiated, and over the next 2 to 3 weeks, oral drug administration may be tapered. In the author’s experience, increasing the dose to >220 μg q 12 hours does not usually result in an improved therapeutic response.
Albuterol usually results in relaxation of airway smooth muscles within 1 to 5 minutes, so the effect is almost immediate. This drug should be used in animals with documented or assumed bronchoconstriction. Symptoms that may indicate bronchoconstriction are wheeze, noisy lower airway breathing, and coughing. Albuterol can be used once daily prior to administering fluticasone or as needed for acute coughing and wheezing. In emergency cases, albuterol can often be used q 30 minutes for up to 4 to 6 hours without serious side effects.
Frequently Asked Questions
What are the side effects of using these drugs?
In people, fluticasone is associated with a change in voice and occasionally a candidal infection within the back of the throat (i.e., thrush).f These side effects have not been observed with any frequency in either the dog or cat. Occasionally, if the mask is improperly placed on a cat’s face, the inspired medication is directed upward toward the lower eyelid, causing conjunctivitis. This is remedied by correct placement of the nasal mask.
Do you need a separate spacer for each drug?
No, one spacer can be used for both medications.
Can I use fluticasone more than twice daily?
There are no data available indicating that increasing the frequency of fluticasone beyond q 12 hours increases the efficacy of the drug.
Can I spray the medication into the spacer first and then put the mask on my pet?
The manufacturers of the spacers have demonstrated that the most efficient means of delivering medication to the airway is to place the mask on the pet’s face prior to actuating the MDI; otherwise, as much as 90% of the drug may be lost.e
Can these drugs be used in animals with diabetes or heart failure?
The inhalation method of delivery is ideal for animals with diabetes mellitus, as the fluticasone is not significantly absorbed into the systemic circulation. Albuterol absorption presents a theoretical risk to animals with heart failure and hypertrophic cardiomyopathy; however, this potential side effect has not been a recognized problem in clinical practice.
Conclusion
The use of inhaled medications to treat asthma and bronchitis is considered the standard of care in humans and is now widely recommended in animals. Over the past 8 years, the author has treated >400 dogs and cats with asthma or bronchitis with inhaled fluticasone and albuterol. Inhalation treatments appear to be practical and safer than the more traditional oral and parenteral drug delivery route. Further studies are indicated to determine whether fewer side effects and increased efficacy occur with inhalation therapies compared to more traditional methods of drug delivery.
Flovent; GlaxoSmithKline, Research Triangle Park, NC 27709
Ventolin HFA; GlaxoSmithKline, Research Triangle Park, NC 27709
Proventil; Schering Corp., Kenilworth, NJ 07033
Aerokat and Aerodawg; Trudell Medical International, Inc., London, Ontario, Canada N5V 5G4
Personal communication, M. Foley, Vice President; Trudell Medical International, Inc., London, Ontario, Canada N5V 5G4
Prescribing information 2005; GlaxoSmithKline, Research Triangle Park, NC 27709
Citation: Journal of the American Animal Hospital Association 42, 2; 10.5326/0420165
Citation: Journal of the American Animal Hospital Association 42, 2; 10.5326/0420165
Photograph of the Aerokat spacer. This device was designed based on a similar instrument used for human infants and was modified to accommodate the specific respiratory pressures and breathing volumes of cats.
Use of the Aerokat device for a cat with asthma. The mask must be held snugly to the cat’s muzzle prior to actuating the metered dose medication to be inhaled.
