TITU MAIORESCU University

Discipline PHARMACOLOGY

General medicine

1st semester
Course notes

DRUG AFFECTING THE

AUTONOMIC NERVOUS SYSTEM
(1)

University year 2020 - 2021 1

 AUTONOMIC NERVOUS
SYSTEM
• formerly the vegetative nervous (ANS)
system

• The autonomic nervous system (ANS), along with the endocrine

system, coordinates the regulation and integration of bodily functions.

• The endocrine system sends signals to target tissues by varying the

levels of bloodborne hormones.

• In contrast, the nervous system exerts its influence by the rapid

transmission of electrical impulses over nerve fibers that terminate at
effector cells, which specifically respond to the release of
neuromediator substances.
 AUTONOMIC NERVOUS
SYSTEM (ANS)
• Drugs that produce their primary therapeutic effect by mimicking or
altering the functions of the autonomic nervous system are called
autonomic drugs and are discussed in the following chapters.

• These autonomic agents act either by stimulating portions of the

autonomic nervous system or by blocking the action of the autonomic
nerves.

• This chapter outlines the fundamental physiology of the ANS and

describes the role of neurotransmitters in the communication between
extracellular events and chemical changes within the cell.
 INTRODUCTION TO THE
NERVOUS SYSTEM
• The nervous system is divided into two
anatomical divisions: the central nervous
system (CNS), which is composed of the
brain and spinal cord, and the peripheral
nervous system, which includes neurons
located outside the brain and spinal cord—
that is, any nerves that enter or leave the CNS.
• The peripheral nervous system is subdivided
into the efferent division, the neurons of
which carry signals away from the brain and
spinal cord to the peripheral tissues, and the
afferent division, the neurons of which bring
information from the periphery to the CNS.
• Afferent neurons provide sensory input to
modulate the function of the efferent division
through reflex arcs, or neural pathways that
mediate a reflex action.
 A. Functional divisions within the nervous
• The efferent portion of the peripheral nervous system is further divided
system
into two major functional subdivisions, the somatic and the autonomic
systems.
• The somatic efferent neurons are involved in the voluntary control of
functions such as contraction of the skeletal muscles essential for
locomotion.
• The autonomic system, conversely, regulates the everyday requirements of
vital bodily functions without the conscious participation of the mind.
• Because of the involuntary nature of the autonomic nervous system as well
as its functions, it is also known as the visceral, vegetative, or involuntary
nervous system.
• It is composed of efferent neurons that innervate smooth muscle of the
viscera, cardiac muscle, vasculature, and the exocrine glands, thereby
controlling digestion, cardiac output, blood flow, and glandular secretions.
 B. Anatomy of the ANS
1. Efferent neurons:

• The ANS carries nerve impulses from the CNS to the effector organs by way of
two types of efferent neurons
• The first nerve cell is called a preganglionic neuron, and its cell body is located
within the CNS.
• Preganglionic neurons emerge from the brainstem or spinal cord and make a
synaptic connection in ganglia (an aggregation of nerve cell bodies located in
the peripheral nervous system).
• These ganglia function as relay stations between a preganglionic neuron and a
second nerve cell, the postganglionic neuron.
• The latter neuron has a cell body originating in the ganglion.
• It is generally nonmyelinated and terminates on effector organs, such as smooth
muscles of the viscera, cardiac muscle, and the exocrineglands.
 B. Anatomy of the ANS

2. Afferent neurons:

• The afferent neurons (fibers) of the ANS are

important in the reflex regulation of this system
(for example, by sensing pressure in the carotid
sinus and aortic arch) and in signaling the CNS to
influence the efferent branch of the system to
respond.
 B. Anatomy of the ANS
3. Sympathetic neurons:

• The efferent ANS is divided into the sympathetic and the parasympathetic nervous systems
as well as the enteric nervous system.
• Anatomically, the sympathetic and the parasympathetic neurons originate in the CNS and
emerge from two different spinal cord regions.
• The preganglionic neurons of the sympathetic system come from thoracic and lumbar
regions (T1 to L2) of the spinal cord, and they synapse in two cordlike chains of ganglia that
run close to and in parallel on each side of the spinal cord.
• The preganglionic neurons are short in comparison to the postganglionic ones. Axons of the
postganglionic neuron extend from these ganglia to the tissues that they innervate and
regulate .
• The sympathetic nervous system is also called the thoracolumbar division because of its
origins. In most cases, the preganglionic nerve endings of the sympathetic nervous system
are highly branched, enabling one preganglionic neuron to interact with many
postganglionic neurons.
• This arrangement enables this division to activate numerous effector organs at the same
time.
 B. Anatomy of the ANS
4. Parasympathetic neurons:

• The parasympathetic preganglionic fibers arise from cranial

nerves III (oculomotor), VII (facial), IX (glossopharyngeal), and
X (vagus) as well as from the sacral region (S2 to S4) of the
spinal cord and synapse in ganglia near or on the effector organs.
• Thus, in contrast to the sympathetic system, the preganglionic
fibers are long, and the postganglionic ones are short, with the
ganglia close to or within the organ innervated.
• In most instances there is a one-to-one connection between the
preganglionic and postganglionic neurons, enabling the discrete
response of this division.
 B. Anatomy of the ANS
5. Enteric neurons:

• The enteric nervous system is the third division of the ANS.

• It is a collection of nerve fibers that innervate the gastrointestinal
(GI) tract, pancreas, and gallbladder, and it constitutes the “brain
of the gut.”
• This system functions independently of the CNS and controls the
motility, exocrine and endocrine secretions, and microcirculation
of the GI tract. It is modulated by both the sympathetic and
parasympathetic nervous systems.
 C. Functions of the sympathetic nervous
• Although continually active to some degree (for example, in maintaining the
system
tone of vascular beds), the sympathetic division has the property of
adjusting in response to stressful situations, such as trauma, fear,
hypoglycemia, cold, and exercise.

1. Effects of stimulation of the sympathetic division:

• The effect of sympathetic output is to increase heart rate and blood pressure,
to mobilize energy stores of the body, and to increase blood flow to skeletal
muscles and the heart while diverting flow from the skin and internal
organs.
• Sympathetic stimulation results in dilation of the pupils and the bronchioles.
• It also affects GI motility and the function of the bladder and sexual organs.
• 2. Fight or flight response:

• The changes experienced by the body during emergencies have been

referred to as the “fight or flight” response .
• These reactions are triggered both by direct sympathetic activation
of the effector organs and by stimulation of the adrenal medulla to
release epinephrine and lesser amounts of norepinephrine.
• Hormones released by the adrenal medulla directly enter the
bloodstream and promote responses in effector organs that contain
adrenergic receptor).
• This system, with its diffuse distribution of postganglionic fibers, is
involved in a wide array of physiologic activities.
• Although it is not essential for survival, it is nevertheless an
important system that prepares the body to handle uncertain
situations and unexpected stimuli.
D. Functions of the parasympathetic nervous
system

• The parasympathetic division is involved with maintaining homeostasis within the

body.
• To accomplish this, it maintains essential bodily functions, such as digestive
processes and elimination of wastes.
• The parasympathetic division is required for life. It usually acts to oppose or
balance the actions of the sympathetic division and is generally dominant over the
sympathetic system in “rest and digest” situations.
• The parasympathetic system is not a functional entity as such and it never
discharges as a complete system.
• If it did, it would produce massive, undesirable, and unpleasant symptoms, such as
involuntary urination and defecation. Instead, discrete parasympathetic fibers are
activated separately and the system functions to affect specific organs, such as the
stomach or eye.
 E. Role of the CNS in the control of autonomic
• Although the ANS is a motorfunctions
system, it does require sensory input
from peripheral structures to provide information on the state of
affairs in the body.

• This feedback is provided by streams of afferent impulses,

originating in the viscera and other autonomically innervated
structures that travel to integrating centers in the CNS, such as the
hypothalamus, medulla oblongata, and spinal cord.

• These centers respond to the stimuli by sending out efferent reflex

impulses via the ANS
• 1. Reflex arcs:

• Most of the afferent impulses are translated

into reflex responses without involving
consciousness.

• For example, a fall in blood pressure causes

pressure-sensitive neurons (baroreceptors in
the heart, vena cava, aortic arch, and carotid
sinuses) to send fewer impulses to
cardiovascular centers in the brain.

• This prompts a reflex response of increased

sympathetic output to the heart and
vasculature and decreased parasympathetic
output to the heart, which results in a
compensatory rise in blood pressure and
tachycardia.
 F. Innervation by the ANS
1. Dual innervation:
• Most organs in the body are innervated by both divisions of the ANS.
• Thus, vagal parasympathetic innervation slows the heart rate, and
sympathetic innervation increases the heart rate.
• Despite this dual innervation, one system usually predominates in controlling
the activity of a given organ.
• For example, in the heart, the vagus nerve is the predominant factor for
controlling rate.
• This type of antagonism is considered to be dynamic and is fine-tuned at any
given time to control homeostatic organ functions.
• The activity of a system represents integration of influence of both divisions.
2. Organs receiving only sympathetic innervation:

• Although most tissues receive dual innervation, some

effector organs, such as the adrenal medulla, kidney,
pilomotor muscles, and sweat glands, receive innervation
only from the sympathetic system.
• The control of blood pressure is also mainly a
sympathetic activity, with essentially no participation by
the parasympathetic system.
 G. Somatic nervous system

• The efferent somatic nervous system differs from

the autonomic system in that a single myelinated
motor neuron, originating in the CNS, travels
directly to skeletal muscle without the mediation of
ganglia.
• As noted earlier, the somatic nervous system is
under voluntary control, whereas the autonomic
system is involuntary. Responses in the somatic
division are generally faster than those in the ANS.
Summary of differences between sympathetic,
parasympathetic, and motor nerves
III. CHEMICAL SIGNALING
BETWEEN CELLS
• Neurotransmission in the ANS is an
example of the more general process of
chemical signaling between cells.
• In addition to neurotransmission, other
types of chemical signaling include the
secretion of hormones and the release of
local mediators
• Local mediators
• Most cells in the body secrete chemicals that
act locally, that is, on cells in their immediate
environment.
• Because these chemical signals are rapidly
destroyed or removed, they do not enter the
blood and are not distributed throughout the
body. Histamine and the prostaglandins are
examples of local mediators.
 Neurotransmitters
• All neurons are distinct anatomic units, and no structural continuity exists
between them.
• Communication between nerve cells, and between nerve cells and effector
organs, occurs through the release of specific chemical signals, called
neurotransmitters, from the nerve terminals.
• This release is triggered by the arrival of the action potential at the nerve
ending, leading to depolarization.
• An increase in intracellular Ca2+ initiates fusion of the synaptic vesicles with
the presynaptic membrane and release of their contents.
• The neurotransmitters rapidly diffuse across the synaptic cleft, or space
(synapse), between neurons and combine with specific receptors on the
postsynaptic (target) cell
 1. Membrane receptors:

• All neurotransmitters, and most hormones and

local mediators, are too hydrophilic to penetrate the
lipid bilayers of target-cell plasma membranes.
• Instead, their signal is mediated by binding to
specific receptors on the cell surface of target
organs.
• Most receptors are proteins.
 2. Types of neurotransmitters:
• Although over fifty signal molecules in the nervous system have tentatively
been identified, six signal compounds, including
• norepinephrine (and the closely related epinephrine),
• acetylcholine,
• dopamine,
• serotonin,
• histamine, and γ
• -aminobutyric acid (GABA),
• are most commonly involved in the actions of therapeutically useful drugs.
• Each of these chemical signals binds to a specific family of receptors.
• Acetylcholine and norepinephrine are the primary chemical signals in the
ANS, whereas a wide variety of neurotransmitters function in the CNS.
• Not only are these neurotransmitters released on nerve stimulation, but also
cotransmitters, such as adenosine, often accompany them and modulate the
transmission process.
 a. Acetylcholine:
• The autonomic nerve fibers can be divided into two groups based on the
chemical nature of the neurotransmitter released.
• If transmission is mediated by acetylcholine, the neuron is termed
cholinergic .
• Acetylcholine mediates the transmission of nerve impulses across autonomic
ganglia in both the sympathetic and parasympathetic nervous systems.
• It is the neurotransmitter at the adrenal medulla.
• Transmission from the autonomic postganglionic nerves to the effector
organs in the parasympathetic system, and a few sympathetic system organs,
also involves the release of acetylcholine. In the somatic nervous system,
transmission at the neuromuscular junction is also cholinergic.
 b. Norepinephrine and
epinephrine:
• When norepinephrine or epinephrine is the transmitter, the fiber is
termed adrenergic (adrenaline being another name for epinephrine).
•
• In the sympathetic system, norepinephrine mediates the
transmission of nerve impulses from autonomic postganglionic
nerves to effector organs.

• A few sympathetic fibers, such as those involved in sweating, are

cholinergic, and, for simplicity, they are not shown in the figure.
Also postganglionic renal smooth muscle is innervated by dopamine.
 IV. SECOND–MESSENGER SYSTEMS
•
IN INTRACELLULAR RESPONSE
The binding of chemical signals to receptors activates enzymatic processes
within the cell membrane that ultimately results in a cellular response, such
as the phosphorylation of intracellular proteins or changes in the
conductivity of ion channels.

• A neurotransmitter can be thought of as a signal, and a receptor as a signal

detector and transducer.

• Second-messenger molecules produced in response to a neurotransmitter

binding to a receptor translate the extracellular signal into a response that
may be further propagated or amplified within the cell.

• Each component serves as a link in the communication between

extracellular events and chemical changes within the cell