Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

18
Drugs used in the management of
respiratory diseases
Philip Padrid and David B Church
INTRODUCTION
The term ‘respiratory disease’ includes any disorder of
the pulmonary tree, including infectious and noninfectious
disease(s) of the nasal cavity and sinuses, posterior
oropharynx, larynx, trachea, bronchi, lung parenchyma
and pleural cavity. This chapter will concentrate primarily
on the drugs used to treat respiratory disease in
dogs and cats in which the primary cause is not due to
infectious or parasitic agents. The reader is referred to
other chapters of this book for specific methods of treating
viral, bacterial, fungal and parasitic infections of the
respiratory tract. Additionally, respiratory dysfunction
due to pulmonary congestion and edema as a result of
primary or secondary heart failure will also be covered
in other appropriate chapters.
CLINICAL SIGNS OF
RESPIRATORY DISEASE
Regardless of the cause, inflammation and/or obstruction
of the respiratory tract results in a relatively small
number of clinical signs. These include sneezing, reverse
sneezing, coughing, gagging, nasal discharge, noisy
breathing, increased (rarely decreased) rate of breathing,
increased or decreased depth of breathing, lethargy
and exercise intolerance. Most respiratory disorders will
cause some combination of these signs to occur simultaneously.
In order to make rational choices for the
treatment of both the signs and the underlying cause(s)
of these signs, it is helpful to briefly review the relevant
pathophysiology.
Pathophysiological regulation of
airway size
The diameter of an airway has a profound effect on the
amount of air that can travel through that airway as
well as the speed with which that air travels.
There are two important clinical messages:
1. decreased airway diameter results in increased
airflow velocity. This, in turn, causes a drop in
airway pressure
2. small changes in airway diameter result in
enormous changes in the amount of air that can
pass through that airway.
Many respiratory diseases cause airway narrowing from
edema, mucus formation or cellular infiltration. Normal
volumes of air may not be able to flow easily on a
breath-by-breath basis and the airways may be prone to
collapse. This phenomenon is one of the causes of noisy
breathing, tachypnea, sneeze, cough, lethargy and exercise
intolerance. Therefore, drug therapy that results in
an increase in airway diameter may minimize or even
abolish these clinical signs.
Airway diameter is also determined by physiological
bronchial tone mediated through nervous airway smooth
muscle innervation. In dogs and cats the primary efferent
system is parasympathetic and the major neurotransmitter
is acetylcholine.
The mechanisms involved in cholinergic bronchoconstriction
are complex and incompletely understood.
Intracellular effects depend in part on modifications of
intracellular levels of cyclic adenosine monophosphate
(cAMP) and cyclic guanosine monophosphate (cGMP).
The effects of these two second messengers are reciprocal;
hence increased concentrations of one are
associated with decreased concentrations of the other.
Cyclic AMP is increased by β 2 -receptor stimulation and
decreased by activation of α-receptors. In contrast, activation
of H 1 -receptors, muscarinic effects of acetylcholine
and a variety of different inflammatory mediators
and increased intracellular Ca 2+ concentrations all
increase cGMP levels.
Acetylcholine’s actions are mediated via a number
of mechanisms, which are not all cAMP or cGMP
dependent. These include increasing intracellular concentrations
of inositol 1,4,5-triphosphate (ITP) and diacylglycerol
(DAG) as well as promoting calcium influx
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