Respiratory Therapeutics
World Small Animal Veterinary Association World Congress Proceedings, 2008
Brendan McKiernan, DVM, DACVIM-SAIM
Southern Oregon Veterinary Specialty Center
Medford, OR, USA

Is there any information that says one particular protocol is better than another... or that this drug really works?? Which antibiotic is best? Am I at risk in using fluoroquinolones in young pneumonic dogs in my practice? How long do I treat for? Are bronchodilators effective? Should I use steroids? Are there newer drug delivery systems/equipment that I should use? No doubt those therapeutic choices can be difficult and confusing. However, establishing a specific diagnosis will make your treatment selection much easier. There are 3 general goals of respiratory therapeutics that I discuss: 1) controlling secretions, 2) maintaining alveolar ventilation and 3) normalizing pulmonary (excessive) reflexes.

Control of Secretions

Secretions may be controlled by either decreasing their production (the best choice) or facilitating the removal of excess, accumulated secretions. Antibiotics and corticosteroids--based on culture and cytology results--are the main methods to decrease secretions. Upper airway cultures (nasal cavity) are rarely helpful as infections there are secondary; tonsillar swabs are not indicative of flora in the lower airways. Chronic bronchitis is not normally associated with significant bacterial growth.

Antibiotics

Use bactericidal antibiotics that have a good spectrum of activity. For upper airway diseases antibiotics with a good gram-positive spectrum are best. Most pathogens in the lower airways (~85+ %) are gram-negative. Amoxicillin or amoxicillin/clavulanate, cephalosporins, doxycycline, potentiated sulfas, and especially the fluoroquinolones are good choices for lower airway infections. The route of administration is a concern for lower airway diseases. If the infection is thought to be tracheobronchial (intra-luminal) then there should be concern about antibiotic penetration into the lumen of the airways (i.e., does the antibiotic actually penetrate into bronchial secretions). Aerosolized antibiotics are helpful in selected cases of infectious tracheobronchitis (specifically those due to Bordetella infections), but are not appropriate as the sole therapy for pneumonic cases.

Corticosteroids

Oral short acting steroids (prednisone or prednisolone) are preferred for ease of dosage adjustments which is import in chronic conditions. Inhaled steroids are now being used frequently although reports show that there indeed is systemic absorption from this form of therapy.

Antifungals

With the availability of new oral antifungals (itraconazole, fluconazole, voriconazole), effective antifungal therapy can be accomplished for most infections (e.g., cryptococcosis). Topical treatment (enilconazole, clotrimazole) is preferred for nasal aspergillosis in dogs but only after the gross fungal plaques have been removed.

Non-specific Methods of Controlling Secretions

Non-specific means of removing secretions including methods designed to 'loosen' secretions (e.g., bland aerosol therapy and expectorants) and those which are designed to improve the rate of their clearance from the tracheobronchial tree (e.g., cough facilitation and chest physiotherapy).

Aerosol Therapy

The goals of this form of therapy is to either loosen secretions (using saline aerosol and always in conjunction with physiotherapy) or to deliver selected drugs into the lower airways. Medications should not be aerosolized unless they are administered directly via a facemask in animals to increase lower airway deposition. There are many concerns about the proper formulation of any aerosol drug; no veterinary aerosol drugs are approved. At a minimum the rule to follow is that only aqueous solutions should be used.

Recently, there has been considerable discussion about the use of metered dose inhalers (MDIs). Although many testimonial cases (mine included!) attest to the efficacy and success of inhaled steroids and bronchodilators, no detailed peer-reviewed articles have been published. The major point with MDIs is the delivery system. In human medicine, considerable time and training is provided to patients to ensure the correct delivery of these aerosols. In veterinary medicine we must rely on spacers (as is needed in infants and children) to hold the aerosolized medications while the animal breathes it in.

Some nasal conditions result in structural abnormalities (nasal polyps, nasopharyngeal webbing) leading to airflow obstruction and secretion accumulation; these must be treated surgically. Destructive rhinitis in cats following chronic viral disease may be associated with significant retained secretions and benefit from simple saline administration (aerosol or nose spray) or when severe and recurring actual physical rhinoscopic debridement.

Non-specific Airway Inflammation (Irritation)

This is one problem which I commonly encounter and has proven difficult to resolve. It is typically characterized by sneezing and a bilateral, slightly opaque to whitish nasal discharge. Diagnostics to document an underlying problem are unrewarding; biopsies show the non-specific lymphoplasmacytic rhinitis we have all grown to hate. Anti-inflammatory therapy (steroids or NSAIDs such as piroxicam) may be used, at least on a trial basis. A change in the dog's environment may also help.

Maintenance of Alveolar Ventilation

Adequate alveolar ventilation is the principal requirement for normal tissue oxygenation and acid-base balance. Physical obstruction of the airways (e.g., with secretions, tissue, dynamic airway collapse, foreign body, tumor etc. will interfere with ventilation and must be treated. Antibiotics, corticosteroids, bronchodilators as well as surgical interventions (soft palate resection, laryngeal/tracheal surgery, foreign body removal) all serve to improve alveolar ventilation.

Normalization of Reflexes

Excessive reflexes of concern include sneezing and reverse sneezing, coughing and airway narrowing reflexes (laryngospasm and bronchospasm). Reflexes are a part of the normal pulmonary defences and should not be suppressed unless they are excessive and/or debilitating.

Coughing is the sudden, violent and often loud ejection of air from the lungs. It is a normal protective reflex, not commonly observed in healthy animals, but necessary in the diseased animal. During a cough, the intrapleural pressure rises dramatically and as a result the intrathoracic airways are compressed. Air is expelled through a narrowed airway and this serves to dislodge irritant materials. Cough is most effective at removing materials from the intrathoracic larger airways, but is not effective in clearing the bronchioles. Coughing is an essential clearance mechanism in lung disease and should not be suppressed unless the cough is dry (non-productive) or physically tiring to the animal, and an attempt has been made to treat a specific cause.

Antitussives

Cough suppression, when indicated, should be started at the recommended veterinary dose for the particular drug and gradually increased to obtain the desired effect as needed. Classes of these drugs include:

 Peripherally acting antitussives including mucosal anaesthetics, mucolytics, demulcents, and perhaps bronchodilators.

 Centrally acting antitussives including narcotic and non-narcotic drugs such as morphine, codeine, hydrocodone, butorphanol and dextromethorphan.

Anti-Inflammatories

Airway inflammation is the cause in many respiratory distress diseases including chronic bronchitis and 'feline asthma'. I prefer to use oral prednisolone and educate the owners as to how and when to adjust their pet's requirements (based on the frequency of coughing). Long acting, repositol steroids (e.g., Depo Medrol) are typically effective as an antiinflammatory in airway disease but should be avoided if possible, due to the inability to quickly increase or decrease the dose requirement which may fluctuate as the disease waxes and wanes over a period of days. In addition repositol steroids have been linked to adverse side effects in cats including diabetes mellitus and congestive heart failure.

Bronchodilators

Pulmonary function testing is used in human medicine to determine the indication for the use of these agents. The indications for using bronchodilators in dogs and cats are therefore subjective, but include historical (chronic cough, wheezing), physical findings (expiratory effort, crackles, increased tracheal sensitivity) as well as radiographic findings (bronchial pattern, diaphragmatic flattening). Beneficial effects of bronchodilators include bronchodilation, increased mucociliary clearance, improved diaphragmatic contractility, decreased pulmonary artery pressure and stabilization of mast cells, to name a few.

There are three types of bronchodilators that have been used in human and veterinary medicine:

 Anticholinergics--these have unwarranted side effects that preclude long-term use.

 Beta-adrenergic agonists--terbutaline (0.625 mg/cat Q12; 1.25-5 mg/dog Q8-12; and albuterol, 20-50 mcg/kg Q8 in dogs) have been recommended in treating chronic obstructive airway disease. Injectable terbutaline (0.01 mg/kg IV/SQ) is used for bronchoconstriction in cats.

 Methylxanthine. Only a few (human) theophylline products have suitable pharmacokinetics to be used in dogs and cats. A major limitation is that studies have shown that dosage recommendations for these drugs are product specific; use caution in extrapolating doses! Animals with airway disease manage to maintain alveolar ventilation and eliminate carbon dioxide, but do so at an increased cost (work of breathing). The work of breathing is of concern in respiratory disease--muscle fatigue is a problem in chronic cases. Theophylline increases diaphragmatic contractility in dogs; it could reasonably be considered in many chronic respiratory cases.

Newer Therapies

Research work in cats has suggested that serotonin (a mediator of cat airway constriction) receptor inhibition (e.g., cyproheptadine) and the use of cyclosporine have been beneficial based on an experimental model of feline asthma. Unfortunately there are as yet no reports of their successful use in clinical cases.

There has been a lot of internet press for using new drug therapies such as leukotriene receptor blockers, or lipoxygenase inhibitors in feline airway disease. Based on 2 separate scientific studies however this class of drugs has not been shown to be effective in cats to date.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Brendan McKiernan, DVM, DACVIM-SAIM
Southern Oregon Veterinary Specialty Center
Medford, Oregon, USA


MAIN : Pharmacology : Respiratory Therapeutics
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