Download ANATOMY AND PHYSIOLOGY OF THE AUTONOMIC NERVOUS

CHEMICAL
MEDIATORS AND THE
AUTONOMIC
NERVOUS SYSTEM
Overview
 The network of chemical signals and
associated receptors by which cells in the
body communicate with one another provides
many targets for drug action, and has always
been a focus of attention for pharmacologists.
 Chemical transmission in the peripheral
nervous system, and the various ways in
which the process can be pharmacologically
subverted (destabilize, unsettle) will be
discussed.
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Overview…
 In addition to neurotransmission, the less clearly
defined processes, collectively termed
neuromodulation, by which many mediators and
drugs exert control over the function of the nervous
system will also be briefly discussed.
 The relative anatomical and physiological simplicity of
the peripheral nervous system has made it the
proving ground for many important discoveries about
chemical transmission, and the same general
principles apply to the CNS
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Overview…
Two major topics to be understood:
 The Autonomic Nervous System
 General Principles of Chemical Transmission
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ANATOMY AND
PHYSIOLOGY OF THE
AUTONOMIC NERVOUS
SYSTEM
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Introduction
 Studies of drug effects exerted upon the
peripheral nervous system or the cells
that it innervates can provide: an excellent introduction to
mechanisms of drug action,
 the rationale behind the use of drugs as
investigative tools or as therapeutic
agents and
 the methods by which the properties of
drugs are measured.
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Introduction….
 Such studies provide a working base
from which to approach the
pharmacology of other body systems
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Learning Objectives
 At the end of the topic the students
should be able to have a reasonable
understanding of the: Basic anatomy and physiology of
the autonomic nervous system and
 Effectors in the ANS
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Anatomy and Physiology of the Efferent
Peripheral Nervous System and its Effectors
 Before understanding how drugs
produce their effects in the body, you
must understand the anatomy and
physiology of the relevant organ
systems.
 The nervous system is subdivided as
shown in the next slide.
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Subdivision of the Nervous
System
Nervous System
Central
Peripheral
Afferent
Efferent
Somatic
AUTONOMIC
Parasympathetic
Sympathetic
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Enteric
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Subdivision of the Nervous
System…
 The Central Nervous System (CNS)
comprises of the brain and spinal
cord.
 The Peripheral Nervous System lies
outside the skull and vertebral column
and comprises 12 pairs of nerves that
emerge from the brain stem (cranial
nerves) plus 31 pairs of nerves that
emerge from the spinal cord (spinal
nerves)
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Subdivision of the Nervous System
…
 Peripheral neurones that carry impulses
towards the CNS are called afferent
neurones while those carrying impulses
away from CNS are called efferent
neurones.
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Subdivision of the Nervous System
…
 The efferent peripheral nervous system
can be subdivided into somatic and
autonomic components.
 The somatic division of the efferent peripheral
nervous system comprises neurones that
emerge from the spinal cord (via the ventral
roots of spinal nerves) to provide excitatory
innervation of skeletal muscle.
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Subdivision of the Nervous System
…
 The region where a somatic motor
neurone closely approaches a skeletal
muscle is known as the skeletal
neuromuscular junction.
 Acetylcholine (Ach) is the chemical
transmitter at this junction.
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Autonomic Nervous System
 In this session, focus will be on the
Autonomic Nervous System which for
a long time has occupied centre stage
in the pharmacology of chemical
transmission.
 Aspects of other systems will be studied
later.
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Basic Anatomy and Physiology
of the ANS
 The ANS consists of three main
anatomical divisions:
-sympathetic
-parasympathetic
-enteric nervous system
 The enteric nervous system comprise of
the intrinsic nerve plexuses of the GIT,
which are closely interconnected with
the sympathetic and parasympathetic
systems.
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Basic Anatomy and Physiology
of the ANS…
 The sympathetic and parasympathetic
systems provide a link between the CNS and
peripheral organs
 Parasympathetic outflow comprises both
cranial and sacral elements. Cranial
parasympathetic outflow is carried in four
cranial nerves: (III oculomotor; VII facial;
IX glossopharyngeal; X vagus)
 Sacral parasympathetic outflow is carried in
the spinal nerves of some sacral segments
(2, 3, 4) of the spinal cord.
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Basic Anatomy and Physiology
of the ANS…
 Sympathetic outflow from the CNS is
thoracolumbar-the preganglionic
neurones emerge from the CNS in the
ventral roots of the spinal nerves of the
first thoracic to third lumbar segments of
the spinal cord
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Basic Anatomy and Physiology of
the ANS …
 The ANS conveys all of the outputs from the
CNS to the rest of the body except for the
motor innervation of skeletal muscle.
 It is largely outside the influence of voluntary
control
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Basic Anatomy and Physiology of
the ANS …
 The main processes regulated by the
ANS are;
 contraction and relaxation of smooth
muscles;
 all exocrine and certain endocrine
secretions;
 the heartbeat;
 energy metabolism, particularly in
liver and skeletal muscle.
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Basic Anatomy and Physiology of
the ANS …
 Therefore, the autonomic division of
the efferent peripheral nervous
system provides excitatory or
inhibitory innervations to cardiac
muscle, smooth muscle and exocrine
glands (its effector cells)
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Basic Anatomy and Physiology of
the ANS…
 The autonomic nervous pathway
between the CNS and the effector cells
comprises two neurones.
 The axon of the first neurone in the
pathway emerges from the CNS and
terminates a short distance from the cell
body of the second neurone in the
pathway.
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Basic Anatomy and Physiology of
the ANS (cont)
 The region where an axon terminal of
the first neurone closely approaches a
dendrite or cell body of the second
neurone is called a synapse.
 In many cases the synapses of
autonomic pathway occur together in
the course of a peripheral nerve.
 The collection of cell bodies in this
region give rise to a swelling of the
nerve known as a ganglion
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Basic Anatomy and Physiology of
the ANS (cont)
 The first neurone in an autonomic
pathway is called preganglionic
neurone and the second cell is called
the postganglionic neurone.
 Acetylcholine is the chemical
transmitter at all autonomic ganglionic
synapses
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Basic Anatomy and Physiology
of the ANS…
 The region where the axon of the
postganglionic neurone closely
approaches its effector cell is called a
neuroeffector junction.
 The chemical transmitter at this junction
may be acetylcholine or
noradrenaline (NA [norepinephrine],
depending on the particular pathway
under consideration.
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Basic Anatomy and Physiology of
the ANS…
 The autonomic division of the efferent
peripheral nervous system is subdivided
into parasympathetic and
sympathetic components according to
the point of outflow of preganglionic
neurones from the CNS
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SummaryBasic Anatomy of the ANS
 The ANS comprises of three divisions:
sympathetic, parasympathetic and
enteric
 Basic (two neuron) pattern of the
sympathetic and parasympathetic
systems consists of pre-ganglionic
neurons with cell bodies in the CNS
and post-ganglonic neurons with cell
bodies in the autonomic ganglion
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SummaryBasic Anatomy of the ANS …
 Parasympathetic system is connected
to the CNS via:
-cranial nerve outflow (III,VII, IX, X)
-sacral outflow
 Parasympathetic ganglia usually lie
close to or within the target organ
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SummaryBasic Anatomy of the ANS…
 Sympathetic outflow leaves the CNS in
thoracic and lumbar spinal roots.
Sympathetic ganglia form two
paravertebral chains, plus some midline
ganglia
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SummaryBasic Anatomy of the ANS …
 The enteric nervous system consists of
neurons lying in the intramural plexuses of
the GIT.
 It receives inputs from sympathetic and
parasympathetic systems but can act on its
own to control the motor and secretory
functions of the intestine.
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Physiology of the ANS
 The autonomic system controls:-
- smooth muscle (visceral and
vascular),
-exocrine (and some endocrine)
secretions,
-rate and force of the heart and
-certain metabolic processes (e.g.
glucose utilization).
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Physiology of the ANS…
 Sympathetic and parasympathetic
systems have opposing actions in some
situations (e.g. control of heart rate, GIT
smooth muscle) but not in others (e.g.
salivary glands, ciliary muscles).
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Physiology of the ANS (cont)
 Sympathetic activity increases in stress
(‘fight-flight or-fright’ response) whereas
parasympathetic activity predominates during
satiation and repose.
 Both systems exert a continuous
physiological control of specific organs under
normal conditions, when the body is at
neither extreme.
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Transmitters of the ANS
 The principal transmitters are acetylcholine
(ACh) and noradrenaline.
 Preganglionic neurons are cholinergic, and
ganglionic transmission occurs via nicotinic
Ach receptors (although excitatory
muscarinic ACh receptors are also present on
postganglionic cells).
 Postganglionic parasympathetic neurons are
cholinergic, acting on muscarinic receptors in
target organs.
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Transmitters of the ANS….
 Postganglionic sympathetic neurons are
mainly noradrenergic, although a few are
cholinergic (e.g. sweat glands).
 Transmitters other than noradrenaline and
acetylcholine (NANC-non-noradrenergic
non-cholinergic transmitters) are also
abundant in the autonomic nervous system.
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NANC-non-noradrenergic noncholinergic transmitters
 The main ones are :-
-nitric oxide and vasoactive intestinal peptide
(parasympathetic),
-ATP and neuropeptide Y (sympathetic).
 Others, such as
-5-hydroxytryptamine (5HT),
-GABA and
-dopamine, also play a role.
 Co-transmission is a general phenomenon.
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 Further Revision
 Read Rang & Dale’s Pharmacology, 7th
Edition, Chapter 12, pg. 139-143
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