Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

ANTITUSSIVES
genes, resulting in up- or downregulation of the gene
and its product. Fluticasone, like other corticosteroids,
acts to inhibit mast cells, eosinophils, lymphocytes, neutrophils
and macrophages involved in the generation
and exacerbation of allergic airway inflammation by
transcriptional regulation of these target genes. Preformed
and newly secreted mediators including histamine,
eicosanoids, leukotrienes and multiple cytokines
are inhibited as well.
Fluticasone is a large molecule and acts topically
within the airway mucosa. Because there is poor absorption
across gut epithelium there is minimal oral systemic
bioavailability, thus plasma levels do not predict therapeutic
effects. This explains the lack of systemic side
effects but it also suggests that clinically effective absorption
into the airway mucosa is delayed. Optimal clinical
effects therefore may not occur for 1–2 weeks.
Fluticasone has been used to treat cats with bronchial
asthma since at least 1993. The first systematic published
report of the use of this drug for this purpose was
in the year 2000. Since then, a number of manuscripts
have demonstrated the clinical effectiveness of fluticasone
to treat dogs and cats with allergic rhinitis,
bronchitis and asthma (naturally occurring and experimentally
induced). There have been no controlled published
studies to determine the optimal dose or interval
for use of fluticasone in dogs or cats. However, there
are anecdotal reports (by one of the authors) that reference
more than 500 small animal patients treated with
fluticasone over a period covering 1995–2006. Dosage
recommendations are therefore based on these anecdotal
reports and are supported by more recent published
studies.
Formulations and dose rates
Inhaled corticosteroids come in multiple forms. However, only the
metered dose inhalers (MDI) combined with a spacer and mask appropriate
for the size of the patient’s muzzle are currently suitable for
use in small animal patients. Fluticasone comes in three strengths:
44/110 and 220 µg per actuation. The authors have found that 44 µg
dosing twice daily does not consistently result in acceptable clinical
responses in either dogs or cats of any size. For cats and dogs less
than 12 kg, 110 µg given twice daily frequently results in clinical
responses equivalent to that achieved by administration of oral doses
of prednisone 5 mg PO BID. Dogs larger than 12 kg may need twice
this dose, or 220 µg inhaled BID.
The choice of spacer is clinically signifi cant because the effi cacy
of a spacer as a delivery device affects the amount of drug available
to the patient. Most mammalian species including dogs and cats have
a tidal volume of 10–20 mL inspired air/kg of bodyweight. Currently,
only the Aerokat ® and Aerodawg ® brand (Trudell Medical Inc, Ontario)
spacers have been designed specifi cally based on the tidal volume
characteristics of small animals. Using these spacer devices, dogs
and cats will inhale the majority of drug propelled into the spacer by
breathing 7–10 times through the spacer– mask combination after
actuation of the MDI. As previously mentioned, it may take 1–2 weeks
to reach maximal clinical effi cacy due to the large size of the molecule
and slow penetration into airway mucosa.
ANTITUSSIVES
Relevant pathophysiology
The cough reflex is complex, involving the central and
peripheral nervous systems as well as the smooth muscle
of the bronchial tree. Chemical or mechanical irritation
of the epithelium within bronchial mucosa causes bronchoconstriction,
which in turn stimulates cough receptors
located within the tracheobronchial tree. Afferent
conduction from these receptors occurs via the vagus
nerve to centers within the medulla that are distinct
from the actual respiratory center.
The drugs that can affect this complex mechanism are
quite diverse. For example, coughing as a result of bronchoconstriction
may be relieved by bronchodilators
acting simply to dilate airways, while other antitussive
agents act primarily on the peripheral or central nervous
system components of the cough reflex. Generally,
however, the most effective antitussives elevate the
threshold for coughing by poorly understood centrally
mediated mechanisms.
Clinical applications
Almost any respiratory tract disorder involving any
level of the large and small airways can result in coughing.
This should normally be viewed as a protective
physiological process resulting in clearance of thick and
tenacious secretions produced by chronic airway inflammation.
Thus, cough suppression as a single therapeutic
agent is relatively contraindicated when cough is associated
with mucus production. In investigating any animal
with suspected respiratory disease, it is important
to establish if the animal gags, chokes or swallows
after coughing. If the answer to any of these questions
is yes, it is likely mucus is being produced and brought
to the caudal pharynx. In these cases, cough suppression
as a single treatment modality is likely to be
contraindicated.
However, once mucus production is diminished or
resolved, cough suppression may be desirable. Chronic
coughing tends to increase airway inflammation,
increasing the risk of a vicious cycle in which the cough
causes mucosal irritation. This can result in further
coughing. Consequently, cough suppression may be
particularly helpful for selected patients, including
dogs with tracheobronchial collapse or dogs recovering
from the acute phase of the kennel-cough complex.
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