Inhalation therapy for respiratory diseases (Proceedings)

The use of inhaled medications is certainly not a new phenomenon in feline medicine. It makes intuitive sense that local delivery of medication might result in different actions than systemic administration. There are two primary methods for delivering inhaled medications to cats: 1) use of metered dose inhalers (MDI) or 2) use of a nebulizer to aerosolize liquid medications.

This main focus of this talk will be to cover the primary indications, clinical use considerations, contraindications, and side effects of medications commonly delivered to cats via MDI, but there will be some brief discussion of nebulization therapy as well.

General information about MDI delivery

Why use inhalation therapy?

One of the most commonly cited reasons for recommending inhaled medications as an alternative to oral/systemic medications is the lack of systemic absorption. Since less (not zero) medication is absorbed, there may be fewer systemic side effects, interactions with other medications, or problems with other co-morbid conditions. Another way to look at this is that if the medication is only needed in the airway, why deliver it to the whole body. In theory it may also be possible to deliver a concentration of medication to the airway that would be impossible to achieve with systemic administration due to other effects of the medication.

Another common reason for using an inhaled medication is that there may be a more rapid onset of action for certain medications. This is certainly not true for all inhaled medications, however, so it is important to be familiar with the specific medications you prescribe.

One final reason for utilizing this method of delivery is that there are certainly patients for which attempts to administer oral medications on a long term basis is impractical, impossible, or detrimental to the human-animal bond between the cat and client.

Delivery of medication

Effective use of a MDI in adult humans requires coordination between device actuation and inhalation. Since this is essentially impossible to achieve in cats (as with small children), an alternative method of delivery is needed that eliminates the need for such coordination. One method that has been developed involves the use of a spacer device which serves as a reservoir for the medication after actuation so that it can then be inhaled by the cat. When using this type of device, the amount of drug that is actually delivered to the lower airways is dependent on a number of factors such as the length, diameter, and total volume of the entire spacer apparatus (MDI, spacer, mask). The Aerokat® brand spacers seem to have appropriate characteristics for delivery of most commonly used MDI products for the average cat and a study utilizing radiolabeled aerosolized particles administered via a spacer device was able to demonstrate that the particles did reach the lower airways.

Even with a spacer, it is still important to follow a consistent protocol for administration of the MDI medications. The MDI should be shaken before use to open an internal valve, then attached to the spacer apparatus. The mask on the other end of the apparatus is then placed over the muzzle of the cat (covering both nose and mouth) before the device is actuated. After actuation, the cat should take 7-10 full breaths before removing the apparatus.

Some medication will settle out or stick to the sides of the spacer apparatus, so it is a good idea to rinse the spacer out regularly. As long as it is cleaned, one spacer can be used for multiple medications (e.g. a steroid and a bronchodilator).

Specific medications

Glucocorticoids— Fluticasone propionate (Flovent)

The most common indication for the use of inhaled medication in cats is non-infectious chronic inflammation of some part of the airway, most commonly rhinitis/rhinosinusitis or feline inflammatory bronchial disease (bronchitis or asthma). In both cases, long term administration of glucocorticoids (typically as oral prednisolone) is one of the most effective treatments available. Although many cats can be successfully managed with very low doses of prednisolone and actually tolerate this therapy very well, there are some individuals or circumstances in which it would be desirable to minimize systemic levels of exogenous steroids.

Fluticasone is the most commonly used inhaled corticosteroid in cats for a number of reasons. It is a synthetic steroid with a very high affinity for corticosteroid receptors (18-fold higher than dexamethasone) and a long half life. It is also poorly bioavailable across GI mucosal epithelium. This is helpful because like any inhaled medication, a substantial part of each dose (up to ~70%) is deposited at the back of the mouth and swallowed. In the case of fluticasone this "lost" portion of the dose seems to have minimal systemic effects, including an apparent lack of hypothalamic-pituitary-adrenal axis suppression. There may also be slow absorption across/into the respiratory epithelium, however, which means that it may take up to a few weeks to see the full clinical effects.

Flovent comes in strengths of 44mcg, 110mcg, or 220mcg per actuation. One recent study demonstrated similar reductions in some markers of airway inflammation no matter which dose was used. This has prompted many clinicians to use the 44mcg dose. However, other authors have suggested that based on their clinical anecdotal observations, there are some cats for which the actual clinical signs cannot be controlled at the 44mcg dose. In either case, doses are typically given twice a day. There has not been any reported benefit to administering this medication more frequently.

The low systemic absorption of fluticasone means that there are relatively few systemic side effects. There can be some adverse effects related to local actions of the drug, although most reports are anecdotal. In humans, pharyngitis and oral candidiasis ("thrush") have been reported as the most likely adverse effects and these would also be potential problems for cats. Some cats may actually have a sensitivity to the medication that results in a cough or bronchospasm/bronchoconstriction after administration. There are also cats that will develop hair loss of skin infections on the part of the face that sits under or right around the mask, and if the mask is not fitted properly, there can also be irritation of the conjunctiva.

Bronchodilators — Albuterol

Albuterol is a selective beta2 receptor agonist available from a variety of manufacturers as a MDI with a dose of 90mcg per actuation. It has a very rapid onset of action after inhalation (1-5 minutes) compared to oral administration (30 minutes), but a shorter duration of action (3-6 hours).

It is not clear how much albuterol might be absorbed systemically after inhalation so the primary rationale for administering this medication by inhalation is the rapid onset of action, rather than avoidance of side effects. However, inhalation probably does allow for the use of smaller doses and it may be a bit safer than systemic administration. Most of the potential adverse effects of inhaled albuterol are similar to those observed with oral dosing.

The most common side effects include tachycardia, tremors, anxiety, or CNS excitement. These effects are probably dose related and temporary. Albuterol should be used with caution in patients with pre-existing cardiac disease (especially cardiomyopathy, CHF, or arrhythmias), diabetes mellitus, hyperthyroidism, hypertension, or seizure disorders. Lastly it is recommended that potassium levels be monitored periodically in cases where chronic therapy is required.

There is currently some controversy about whether the inhaled formulation of albuterol can be safely administered as chronic therapy for lower airway disease. Research in people and research cats has shown that chronic administration of albuterol may actually induce or increase some markers of airway inflammation. The most likely explanation for this is that albuterol is composed of a 1:1 mixture of an R-enantiomer (which has bronchodilatory and anti-inflammatory effects) and an S-enantiomer (which seems to have pro-inflammatory effects and may contribute to airway hyperreactivity and bronchoconstriction). The S-enantiomer appears to be metabolized more slowly and is therefore preferentially retained in the lungs. It does not appear that this is a problem with single or short term dosing.

It should be noted that some clinicians have argued that the experimental evidence of increasing inflammation with chronic administration of racemic albuterol may not actually translate to clinically relevant problems in patients with inflammatory airway disease, especially if they are receiving anti-inflammatory doses of glucocorticoids concurrently. Although there are no clinical studies to help determine actual clinical outcomes, it seems reasonable that chronic use of racemic albuterol should limited to situations where quality of life would otherwise be adversely affected and that it should certainly not be used as long term monotherapy for inflammatory airway disease.

There is a different product called Levalbuterol (Xopenex) which contains only the R-enantiomer of albuterol and should theoretically limit the risk of inducing airway inflammation with chronic use. The main drawback to use of this medication is that it is significantly more expensive. There is also less documented experience and information about the effects of this medication in cats, although in my limited experience with it, it seems to be well tolerated.

One last consideration is that, while we know that inhaled medications delivered by MDI via a spacer apparatus can reach the lower airway in normal cats, we do not know how much of a given dose might reach the lower airways in a cat with a reduction in airflow due to ineffective respiration. Albuterol is typically administered with the intent to relieve clinical signs associated with spontaneous bronchoconstriction and is often chosen due to its short time to onset of action, but there may be some cases in which the onset is slower or the drug is unable to promote the desired response due to lack of effective delivery. If there are questions about this in a clinical case, an alternative medication and route of administration (e.g. injectible terbutaline) should be considered, or the dose of albuterol may have to be repeated relatively frequently (q30minutes) until a positive response is observed.