1. CHEMICAL MEDIATORS AND THE AUTONOMIC NERVOUS SYSTEM

2. 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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3. 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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4. Overview… Two major topics to be understood:
The Autonomic Nervous System
General Principles of Chemical Transmission
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5. ANATOMY AND PHYSIOLOGY OF THE AUTONOMIC NERVOUS SYSTEM
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6. 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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7. Introduction….
Such studies provide a working base from which to approach the pharmacology of other body systems
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8. 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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9. The nervous system is subdivided as shown in the next slide.
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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10. Subdivision of the Nervous System
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11. 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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12. 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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13. 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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14. 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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15. 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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16. 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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17. 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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18. 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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19. 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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21. 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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22. 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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23. 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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24. 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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25. 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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26. 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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27. 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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28. Summary- Basic 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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29. Summary- Basic 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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30. Summary- Basic 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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31. Summary- Basic 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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32. 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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33. 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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34. 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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35. 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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36. 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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40. NANC-non-noradrenergic non-cholinergic 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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42. Read Rang & Dale’s Pharmacology, 7th Edition, Chapter 12, pg. 139-143
Further Revision
Read Rang & Dale’s Pharmacology, 7th Edition, Chapter 12, pg
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