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Inhalant drug therapy (Proceedings)

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Apr 01, 2010

Inhalant delivery of aerosolized medication offers a number of theoretical benefits including an enormous absorptive surface area across a permeable membrane, a low enzyme environment that results in little drug degradation, avoidance of hepatic first-pass metabolism, and reproducible absorption kinetics. When the target of inhaled medications is the respiratory tract itself, additional benefits include the potential for a high drug concentration directly at the site of disease with minimization of systemic toxicity, often at a fraction of the dose required if the same drug was administered through a systemic route. Because of these advantages, inhalant delivery of medication has gained widespread use for the treatment of airway diseases in people. There is an enormous body of evidence in the medical literature regarding inhalational drug therapy in people. More recently, efforts have been made to evaluate the role for aerosol delivery of medication for the treatment of dogs, and especially cats, with respiratory disease.

Although there are benefits to inhalant drug delivery, there are difficulties in using this route as well. Respiratory defenses are efficient at preventing particulates from reaching the lower airways so it should come as no surprise that only a small proportion of the administered medication reaches the lower airways; a significant amount of drug is lost in the delivery device or deposited in the oropharynx. Another difficulty is that most aerosol drug delivery devices are designed to be used by humans on a voluntary basis and some require purposeful respiration and breath holding. Adaptations of some devices facilitate their use in animals, and modified systems are now marketed for dogs and cats. Drug delivery by the aerosol route depends in part of respiratory depth and rate, tidal volume, and airflow rates, yet all of these may be negatively impacted by respiratory disease. Additionally, not all drugs are suitable for aerosol delivery, and drugs themselves (or preservatives contained in the drug preparation) may cause airway irritation and possible bronchoconstriction potentially worsening respiratory compromise.

Aerosol delivery systems

There are two very basic types of aerosol delivery systems in common usage; nebulizers and metered dose inhalers (MDI). The two are quite distinct devices, and have distinct uses. In general, nebulizers deliver much smaller particles allowing deeper respiratory penetration and provide fluid along with drug. MDI devices deliver drug primarily to the larger airways. There are more than 30 drugs available as MDI, including anti-inflammatory drugs and bronchodilators.

Nebulizers utilize compressors to generate relatively high air pressures and flow rates. Generally, there is a source of compressed air or oxygen, a well into which fluid/drug can be placed, and a baffle which when hit by the drug causes the creation of small particles. The basic nebulizer types include jet nebulizers and ultrasonic nebulizers. Modifications exist (eg, spinning disc nebulizers, vibrating mesh nebulizers) to improve delivery or modulate particle size. Nebulizers are available in portable sizes of a modest price, certainly suitable for use in veterinary hospitals and even practical for at-home use by owners. Cost can begin at under $100 for a good nebulizer unit. Veterinary specific nebulizer units are available for purchase (eg, Trudell Medical). Nebulized liquid can be administered to dogs and cats by face mask, by tent, in a closed aquarium type container into which the animal is placed, or into a tracheotomy tube. Any of these should be suitable for airway humidification via saline nebulization. In general, the more removed the particle generator is from the respiratory tract the more drug would be expected to be lost outside of the respiratory tract. For this reason, administration of drugs via nebulization would likely be more effective by mask than when simply administered into a tank containing the pet.

MDI are designed for at-home administration of aerosolized drugs and are the preferred routine route of delivery for glucocorticoid and bronchodilator medications in people with asthma. Particles delivered by MDI are larger than those created by nebulization, and thus do not penetrate as deeply into the respiratory tract. A traditional MDI consists of a mouthpiece and an actuator (holder) into which a canister of medication is inserted. Manually depressing the canister (actuation) results in the release of a single dose of medication (sometimes called a "puff"). People shake the canister, exhale deeply, insert the mouth piece, and simultaneously depress the canister and inhale as deeply as possible. They then hold their breath for as long as possible, exhale, and rinse the mouth and spit to remove the majority of the drug deposited in the oropharynx (only ~10% of each dose reaches the airways). Obviously, dogs and cats can't use a MDI in this way. Spacers devices designed to fit the MDI have allowed their adaptation for use in animals. Several types of spacers are available, from simple tubes inserted between the MDI and the mouth/nose to holding chambers with one-way valves activated by inhalation. Spacers were designed for young children or others with less than ideal coordination so that there is no requirement for simultaneous depression of the canister and inhalation. The spacer also has the advantage of allowing the largest particles to fall out and not enter the patient's mouth. In people, spacers actually improve drug delivery by ~10%, nearly doubling the amount of drug reaching the target site.

Until recently, most MDI used chlorofluorocarbons as propellants. Concerns about the ozone layer have led to new technologies, including alternate propellants and the use of dry powder inhalers (DPI). The DPI devices contain no propellant, but rely on the patient's inhalation through a reservoir containing the dry power dose. The most common types of DPIs are "discus" inhalers and "turbohalers". Because they do not use a spacer device and require a voluntary inhalation of a minimum force to deliver drug these devices may be less useful for small animal patients than MDI attached to spacers. The change to newer formulations of MDI has dramatically increased the cost of some medications formerly available as inexpensive generic prepeartions.