Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

The pharmacology of the autonomic
nervous system
Matthias J Kleinz and Ian Spence
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The investigation of the autonomic nervous system
has played a central role in the development of modern
pharmacology and formed the basis for establishing
fundamental pharmacodynamic principles that govern
drug actions. At the same time, the identification and
characterization of the major transmitter pathways in
the autonomic nervous system, using classic isolated
organ preparations (e.g. guinea pig ileum), was the
initial step towards the development of a plethora of
drugs that modify autonomically controlled body
functions such as the regulation of the cardiovascular
system, respiratory system and gastrointestinal tract. It
therefore comes as no surprise that drugs modulating
autonomic function in humans, e.g. antihypertensives
and antiasthmatics, have some of the largest markets for
therapeutic agents worldwide. For these obvious reasons
autonomic pharmacology occupies a large section in
most general pharmacology texts and the increasingly
widespread use of such classes of drugs in veterinary
practice requires adequate presentation of autonomic
nervous system pharmacology in textbooks written for
veterinarians.
As a result, this chapter aims to outline the important
basic features of the autonomic nervous system and its
pharmacology and proceeds to discuss in detail those
topics directly relevant to small animal therapeutics. A
reference guide to the clinical use of drugs acting on
the autonomic nervous system forms the end of the
chapter.
Due to the widespread impact of autonomic regulator
pathways on a multitude of organ systems, many drugs
that interact with the autonomic nervous system are also
described in more detail in other chapters.
ANATOMICAL ORGANIZATION OF THE
AUTONOMIC NERVOUS SYSTEM
The autonomic nervous system (ANS) comprises one of
two efferent components of the peripheral nervous
system (PNS). As a part of the PNS, the ANS is responsible
for the efferent innervation of all tissues apart from
skeletal muscle, which itself is innervated by the somatic
nervous system. The predominantly involuntary control
of organ function by the autonomic nervous system is
modulated by neuronal networks which are located
mainly in the brainstem and spinal cord.
The organization of the efferent arm of the somatic
nervous system is essentially uniform. The ANS, on the
other hand, is divided into the sympathetic and parasympathetic
nervous systems. This division is also
reflected in the anatomical origin of sympathetic and
parasympathetic outflow from either thoracolumbar or
craniosacral segments of the central nervous system
(CNS) respectively. The parasympathetic outflow to all
autonomically regulated organs except the bladder,
rectum and genitals (supplied by the pelvic ganglia)
originates from the nuclei of four cranial nerves. These
are the occulomotor nerve (III, structures of the eye),
facial and glossopharyngeal nerves (VII, IX, salivary
glands and nasopharynx) and the vagus nerve (X, thoracic
and abdominal viscera). Figure 4.1 schematically
illustrates the basic anatomical organization of the
ANS.
Another important organizational characteristic that
distinguishes the ANS from the somatic nervous system
is the presence of a neuronal chain of one preganglionic
and one postganglionic neurone in the ANS supplying
the target organs, compared to a single somatic motor
neurone innervating skeletal muscle fibers. This has
some pharmacological importance, as certain drugs act
on postganglionic neurones located in autonomic ganglia
to modulate postganglionic ANS neurotransmission.
The only exception to this ‘two-neurone’ rule of ANS
organization is the sympathetic innervation of the
adrenal medulla. The catecholamine-secreting chromaffin
cells of the adrenal medulla are modified sympathetic
postganglionic neurones, which therefore receive
sympathetic input only from preganglionic sympathetic
axons.
The cell bodies of preganglionic neurones are located
in the sympathetic and parasympathetic nuclei of
the brain and spinal cord. Postganglionic neurone
cell bodies are located mainly in the paravertebral or
prevertebral ganglia (sympathetic outflow) and in
cranial, cervical and pelvic ganglia or in small ganglia
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