PHARMACOLOGY OF THE

AUTONOMIC NERVOUS SYSTEM

 Learning objectives

■ List the neurotransmitters of the

autonomic sympathetic nervous system
and describe their anatomical location
■ List the receptors and receptor-subtypes
of the autonomic sympathetic nervous
system
■ Predict the responses to activation and
inhibition of autonomic sympathetic
nervous system receptors
 ANS
• The nervous system is divided into two
anatomical divisions:
• (i) Central nervous system (CNS) which
consists of:
• Brain
• Spinal cord
• (ii) Peripheral nervous system (PNS;
neurons outside the CNS) which consists
of:
• Afferent division – neurons which bring
signals from the periphery to the CNS
• Efferent (motor) division - neurons
carrying signals away from the brain
and spinal cord to the peripheral
tissues
• The efferent division is further divided into two major subdivisions:
• Somatic: The somatic nervous system differs from the autonomic system
in that it consist of a single myelinated motor neuron, originating in the
CNS; the neuron travels directly to skeletal muscle without the mediation
of ganglia. The somatic nervous system is under voluntary control,
whereas the autonomic nervous system is an involuntary system.
• Autonomic (ANS): This is also called the visceral, vegetative, or
involuntary nervous system. It is largely autonomous (independent) in
that its activities are not under direct conscious control and it is
concerned primarily with visceral (organs in the abdominal cavity)
functions that are necessary for life such as cardiac output, blood flow to
various organs, digestion, etc.
• ANS is further subdivided into three systems, i.e:
• Sympathetic nervous system
• Parasympathetic nervous system
• Enteric nervous system

EFFERENT DIVISION
 ANATOMY OF
• THE
There are twoANS
types of efferent ANS
neurons responsible for transmitting nerve
impulses from the CNS to the effector
organs:
• 1) Preganglionic neurons:
• They 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). Their cell
bodies are located within the CNS.
• 2) Postganglionic neurons
• The latter neurons have cell bodies
originating in the ganglia. They are
generally non-myelinated and
terminate on effector organs, such as
smooth muscles of the viscera, cardiac
muscle, and the exocrine glands.
• It prepares the body in response to stressful situations, such as trauma, fear,
hypoglycemia, cold, or exercise
• Stimulation of the sympathetic division increases the heart rate and blood pressure
thus mobilising energy stores of the body
• Also increase the blood flow to skeletal muscles and the heart, while diverting the
blood flow from the skin and internal organs
• “Fight or flight” response (in emergency) triggered both by direct sympathetic
activation of the effector organs, and by stimulation of the adrenal medulla to
release adrenaline (A) and lesser amounts of noradrenaline (NA)
• NA & A enter the bloodstream and promote responses in effector organs that
contain adrenergic receptors throughout the body

FUNCTIONS OF THE SYMPATHETIC NERVOUS

SYSTEM
• The parasympathetic division maintains essential bodily functions required
for life such as the conservation of energy & maintenance of organ function
during periods of minimal activity
• It usually acts to oppose or balance the actions of the sympathetic division
• It is generally dominant over the sympathetic system in "rest and digest”
situations
• The parasympathetic division slows the heart rate, lowers the BP, stimulates
the GIT movements & excretion, aids absorption of nutrients, protects the
retina from excessive light, & empties the urinary bladder & rectum

Functions of the parasympathetic nervous system

ORGAN INNERVATION
• Most organs in the body are innervated by both divisions of the
autonomic nervous system (sympathetic & parasympathetic)
• Despite this dual innervation, one system usually predominates in
controlling the activity of a given organ e.g. in the heart, the
parasympathetic is the predominant factor for controlling the heart
rate

• Organs receiving only sympathetic innervation:

• some effector organs, such as the adrenal medulla, blood vessels,
and sweat glands, receive innervation only from the sympathetic
system
ORGAN
INNERVATION
CHEMICAL SIGNALING
BETWEEN CELLS
• Chemical communication between cells (including those of the ANS) occurs through the use of chemical
mediators which are classified as follows:
• Local hormones:
• Secreted by most cells in the body
• They act locally and are rapidly destroyed; they do not enter the bloodstream e.g. histamine
secreted by the mast cells during inflammation
• Hormones:
• Secreted by the endocrine glands into the bloodstream distributed throughout the body
• Neurotransmitters:
• Released from the nerve terminals - triggered by the arrival of the action potential at the nerve
ending
• They are responsible for the communication between:
• the nerve cells (ganglion), and nerve cell and the effector organ (neuroeffector)
• They rapidly diffuse across the synaptic cleft or gap (synapse) and combine with (bind to)
specific receptors on the postsynaptic (target) cell. Like local hormones, they are rapidly
destroyed
• Six most common NT are noradrenaline (NA), acetylcholine (Ach), dopamine (DA), serotonin (5-HT),
histamine (H), & gama-aminobutyric acid (GABA)
• Each of these NT binds to a specific family of receptors
• Ach and NA are the primary chemical signals in the ANS; others function mostly in the CNS
 NEUROTRANSMI
TTER CHEMISTRY
OF THE ANS
• Autonomic nerves are classified on
the basis of their primary
transmitter molecules:
• Acetylcholine (Ach)
• Noradrenaline (NA)
• Nerves that synthesise and release
Ach are referred to as cholinergic
neurons (fibers), while those
synthesising and secreting NA are
referred to as noradrenergic (or
simply “adrenergic”) fibers
Ach is a NT at autonomic ganglia in both
the sympathetic and parasympathetic
nervous systems

Also a NT at the adrenal medulla where it

modulates the sympathetic nervous CHOLINERG
system
IC
Also act at autonomic neuroeffector
junction (between postganglionic nerves TRANSMISS
and the effector organs) in the
parasympathetic nervous system ION
In the somatic nervous system,
transmission at the neuromuscular junction
(that is, between nerve fibers and
voluntary muscles) is also cholinergic
NA is a transmitter at autonomic
neuroeffector junction (between
postganglionic nerves and the effector
organs) in the sympathetic system, with
the exception of the sweat glands where

ADRENERG
the neurotransmitter is Ach

IC FIBERS
Both NA and A are also synthesised and
released by the adrenal medulla
following cholinergic stimulation to
control (increase) BP
• All neurotransmitters are too hydrophilic to
penetrate the cell membranes lipid bilayer of AUTONOM
target-cell
IC
• Instead, their signal is mediated by binding to
specific receptors on the cell surface of target RECEPTO
organs
RS
• There are two main types of receptors in the
ANS:
• Cholinergic receptors
• Adrenergic receptors
• The primary ACh (cholinergic) receptor subtypes were named after the alkaloids
originally used in their identification:

• 1. Muscarine - Muscarinic receptors (M)

• Found mostly as postsynaptic membranes of effector organs in the parasympathetic
nervous system. Further subdivided into M1-4

• 2. Nicotine – Nicotinic receptors (N)

• Found autonomic ganglia of, Sympathetic, Parasympathetic nervous system, and Adrenal
medulla. Also found postsynaptically in neuroeffector membrane in the somatic nervous
system
• Further subdivided into NN & NM

CHOLINERGIC RECEPTORS
• Adrenoceptor or simply adrenergic receptors respond to
catecholamines such as NA, A, & DA

• The adrenoceptors can be subdivided into two main

ADRENER
divisions on the basis of their agonist and antagonist
selectivity:
GIC
RECEPTO
• 1. Alpha-adrenergic receptors (α-ARs)
•
RS
Further subdivided into α1-& α2-ARs
• The rank order of potency of agonists for α-ARs
is A > NA ≥ isoproterenol

• 2. Beta-adrenergic receptors (β-ARs)

• Further subdivided into β1-, β2- & β3-ARs
• The rank order of potency of agonists for β-ARs
is isoproterenol > A ≥ NA
BLOOD PRESSURE CONTROL
MECHANISMS
• Blood pressure (BP) is a product of the total peripheral resistance and cardiac output
• Both the parasympathetic as well as sympathetic nervous system are involved in
control of blood pressure via feedback mechanisms
• Changes in BP are detected by baroreceptors, which relay the information to the
cardiovascular centers in the brainstem controlling parasympathetic and sympathetic
outflow
• E.g. and increase in BP elicits baroreceptor discharge, resulting in increased
parasympathetic activity, leading to bradycardia and decreased sympathetic
activity, which in turn leads to decreased heart rate, force of contraction and
vasoconstriction
• This decreases cardiac output and total peripheral resistance and ultimately lowers
BP to normal levels
• Conversely, a decrease in BP elicits feedback involving decreased parasympathetic
outflow and increased sympathetic activity – leading to increase in cardiac output
and total peripheral resistance causing an increase in BP
 ■ The sympathetic and parasympathetic
divisions of the autonomic nervous system
have opposing effects in many tissues

SUMMAR
■ Drugs that activate one division often have
the same effect as drugs that inhibit the
other division

Y OF ■ Acetylcholine (Ach) is the primary

neurotransmitter at parasympathetic and

IMPORTA somatic neuroeffector junctions

■ Noradrenaline (NA) or norepepinephrine, is

NT the transmitter at most sympathetic

junctions

POINTS
■ Most autonomic drugs activate or block
receptors for Ach or NA in smooth muscle,
cardiac tissue, and glands – these are called
direct-acting drugs
■ A few drugs affect neurotransmitter
synthesis, storage, release or metabolism –
these are called indirect-acting drugs
 Practical scenario

A 47-year old woman is given a drug to treat her overactive bladder. She is told that
the drug will decrease her frequency of urination. She is cautioned to be aware of
the possibility of dry eyes, dry mouth, blurred vision, constipation, drowsiness,
dizziness and confusion.

1. Which division of the autonomic nervous system does this drug affect?
2. Describe the organ innervation resulting in all the effects above.
3. What are the differences between the sympathetic and the parasympathetic
nervous systems?
4. What is the enteric nervous system?
5. What are the steps involved in the transmission of a nerve impulse?
6. Why does this drug have such a wide range of adverse effects?