Autonomic nervous system

• The nervous system can be divided anatomically into

• 1. central nervous system (CNS) : it consists of the brain and the

spinal cord

• 2. peripheral nervous system: it consists of the peripheral

nerves

• It can also be divided physiologically into

• 1. somatic nervous system

• It controls voluntary movements by the skeletal muscles

• 2. autonomic nervous system (involuntary or self controlling)

• It regulates visceral activity e.g. heart , digestive system ….etc
• Both systems have a central and peripheral part . The neuron is
the atomic unit of the nervous system.
2 nd year Phamacy (2006-2007) 3
Organization of the nervous system
Nervous system

Central NS Peripheral NS

Autonomic NS Somatic NS

Sympathetic NS Parasympathetic NS

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 Somatic pathway

AHC

5
LHC

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 The reflex arc
• It is the functional unit of the nervous system. It consists of:
• 1. a receptor (sense organ)
• It is a specialized structure sensitive to changes inside or outside the
body. It converts different forms of energy into nerve impulses e.g.
rods and cones in the eye, taste buds in the mouth.
• 2. an efferent neuron
• It carries the nerve impulses from the receptor to the CNS
• 3. center
• It is present inside the CNS
• 4. an efferent neuron
• It carries the impulses from the center to the effector organ
• 5. an effector organ
• It is the structure , which produces the response (e.g. gland or muscle)
 Types of reflex arc
• 1. somatic reflex arc

• E.g. stretch reflex and withdrawal reflex

• a) stretch reflex
• When a skeletal muscle is stretched ; it contracts ( e.g. knee jerk and ankle
jerk)

• b) withdrawal reflex
• When a painful stimulus is applied to the skin , there will be contraction of the
flexor muscles and inhibition of the extensor muscles e.g. pin prick to the skin
leads to sudden withdrawal of the limb.

• 2. autonomic reflex arc

• The autonomic reflex arc differs from the somatic reflex arc mainly in that it
has two efferent neurons.
Differences between somatic and autonomic
reflex arcs
Somatic reflex arc Autonomic reflex arc

The receptor Usually in the skin Usually in a viscus

The afferent Passes via a dorsal root or The same like the somatic reflex arc
neuron cranial nerve and has its cell
body in the dorsal root ganglion.
The center The anterior horn cell The lateral horn cell

The efferent It is composed of one neuron It is composed of two neurons . It passes

neuron only with the spinal nerves and relay in
autonomic ganglia. Before relay , it is
called white ramus communicants
(myelinated) . After relay , it is called
postganglionic neuron (also called gray
ramus communicants) {unmyelinated}
The effector A skeletal muscle Usually a viscus ( plain or cardiac muscle
or a gland)
 Autonomic ganglia

• These are nerve cells present outside

the central nervous system. The axons
of the lateral horn cells (preganglionic
fibers) make synaptic connections with
the cell body of the autonomic ganglia
(synapse) then postganglionic fibers
carry the impulses to the viscera.
 Types of autonomic ganglia
• According to their sites they are classified into

• 1. paravertebral (lateral)
• There are two lateral chains on each side of vertebral column. They are sympathetic only.
The chain contains on ganglion for each segment of the spinal cord, except in the upper
and lower parts of the chain adjacent ganglia fuse together. Thus in the cervical region
there are only 3 ganglia instead of 8 . They are called superior, middle and inferior
cervical sympathetic ganglia.

• 2 . collateral
• They lie between the sympathetic chain and the viscera. They lie at the origin of big
arteries. They may be sympathetic or parasympathetic.

• 3. terminal
• They lie within the wall of organ they supply. They are parasympathetic only.
 Function of the autonomic ganglia
• They act as distributing centers because each preganglionic axon
diverge to many post ganglionic neurons. It is a relay station.

• - in the sympathetic system , the preganglionic fibers relay in the

lateral or collateral ganglia and each preganglionic fiber activates
many postganglionic neurons. This allows for widespread distribution
of nerve impulses producing generalized sympathetic effects.

• -in the parasympathetic system , the preganglionic fibers relay in

collateral or terminal ganglia and each preganglionic fiber activates
few postganglionic neurons. This distribution produces localized
parasympathetic effects.
 Autonomic ganglia
• It is a collection of neurons
outside the CNS.
• It is the site of synapse
between the preganglionic
and the postganglionic
neurons.
• It act as a distributing
center.

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Lateral and collateral ganglia

2006-2007 18
 Parasympathetic NS is characterized by:
*The preganglionic fibers synapse in the
terminal ganglia.
.Long preganglionic fibers*
The postganglionic effects are mediated *
. through acetyl choline

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 Sympathetic NS
• Sympathetic division of
the ANS is called the
fight and flight
division.
• It prepare the body to
deal with stress.

2 nd year Phamacy (2006-2007) 20

Parasympathetic NS

• Parasympathet
ic NS is called
the rest and
sleep division
of the ANS.
• It allows the
body to
recover from
stress
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 Sympathetic nervous system

• Thoracolumber:

• It consists of two neurons, pre and post ganglionic . The

preganglionic neurons have their cell bodies in the lateral
horn of all the thoracic segments and the upper 3 lumber
segments of the spinal cord. The postganglionic neurons
have their cell bodies in the lateral or collateral ganglia.
Then the post ganglionic fibers supply the effector organs.
 Effects of stimulation of the sympathetic nervous system

Organ Effects
Head and neck -motor to lator pupillae muscle leading to dilation of the eye
pupil. di
-secretion of small volume of viscid saliva.
-constriction of the skin blood vessels.

Thorax Stimulation of all properties of the heart:

-Heart -increased heart rate.
-increased force of contraction.
-dilation of the coronary vessels.
-dilation of the bronchi.
-lungs -slight constriction of the pulmonary vessels.
Abdomen Constriction of the blood vessels of the viscera.
-Liver Stimulation of glycogenolysis ( increase in blood glucose
level).
-Stomach and intestine
-decreased motility and decreased secretion
-Gall bladder and bile Increase in tone of sphincters i.e. contraction of sphincters..
ducts -relaxation of the wall and contraction of sphincter.
-Adrenal medulla -stimulation of epinephrine and norepinephrine secretion.
 CONTINU.SYMPATHETIC
functions
-Constriction of the blood vessels of the viscera.
-inhibitory to the wall of the urinary bladder , motor to the sphincter
causing retention of urine.
pelvis
-inhibitory to the wall of the rectum, motor to the sphincter causing
retention.
-in the male, motor to the plain muscles of the vas deferens , seminal
vesicles and prostate causing ejaculation of semen.

Limbs, thoracic -constriction of the skin blood vessels.

and abdominal -dilation to the muscle blood vessels.
walls. -excess secretion of sweat glands.
-contraction of piloerector muscles.
-skeletal muscles glycogenolysis , increased strength of
contraction
- Increased mental activity
General effects - increased BMR ( basal metabolic rate)
-increased blood coagulation
-Increased blood glucose level.
 Alarm or stress function of the sympathetic nervous system

• In emergency states , there is increased sympathetic stimulation. This provides

the body with extra – activities i.e. there is mass sympathetic discharge e.g. in
emotions, muscular exercise , fight and haemorrhage.
 Stress response
• These stress reactions are :
• 1. dilation of the eye pupils, so more lights enters the eyes.
• 2. increase heart rate and force of contraction
• 3. increase arterial blood pressure , so more blood passes to
vital organs and muscles.
• 4. dilation of the bronchi causing better lung ventilation
• 5. constriction of the blood vessels of the skin , gut, kidneys
and spleen i.e. shift of blood from unimportant organs to
important organs.
• 6. increase mental activity
• 7. increase blood glucose level to supply more energy
• 8. increase muscle strength.
• 9.secretion of epinephrine and norepinephrine by the adrenal
medulla. This potentates the effect of sympathetic stimulation.
 Parasympathetic nervous system

• Craniosacral

• It consists of two neurons , pre and post ganglionic neurons

• 1. cranial part:

• - the preganglionic neurons have their cell bodies in the nuclei of III , VII , IX
and X cranial nerves.
• 2. sacral part

• - the preganglionic neurons have their cell bodies in the lateral horn of 2, 3, 4
sacral segments of the spinal cord.
• - the postganglionic neurons of both cranial and sacral parts have their cell
bodies in collateral or terminal ganglia. Then postganglionic fibers supply the
effector organs.
 Effect of stimulation of the parasympathetic nervous system
Parasympathetic
nerves
Oculomotor nerve {third
cranial nerve } (III )
Facial nerve {seventh
cranial nerve} ( VII )
Glossopharyngeal nerve
{ninth cranial nerve} (IX )
effects
-motor to sphincter pupillae muscle leading to
constriction of the eye pupils.
-motor to the ciliary muscle causing accomodation for
near vision.
-vasodilation to the lacrimal , submaxillary and
sublingual salivary glands.
-stimulation of secretion from the lacrimal glands.
-stimulation of profuse watery secretion from the
sublingual and submaxillary salivary glands.
-vasodilation to the blood vessels of anterior 2/3 of
tongue.
-vasodilation to parotid salivary gland.
-stimulation of profuse watery secretion from the
parotid gland.
-vasodilation to the blood vessels of the posterior 1/3 of
the tongue.
Vagus nerve { tenth -Inhibition to all properties of the heart.
cranial nerve} ( X ) --constriction to the coronary blood vessels.
Heart -Bronchoconstriction.
-Dilation to the bronchial blood vessels.
Lungs
-Increases mucus secretion in the respiratory air passages.

-stimulation of peristalsis of the esophagus, stomach , small

intestine and proximal half of the large intestine i.e. increased
motility.
GIT -inhibition to me sphincters of the gastrointestinal tract i.e.
decreased tone of sphincters.
-secretory to the stomach , pancreas and liver i.e. increased
secretion of the GIT.
-contraction of the gall bladder wall and inhibition of its sphincter.
The sacral autonomic -contraction of the muscle of the urinary bladder and relaxation of
nerve { second , third its sphincter causing micturation.
and fourth sacral -contraction of the distal half of the large intestine and rectum and
segments } relaxation of its sphincter causing defecation.
-vasodilation to the blood vessels of the pelvic, viscera causing
erection. So it is called the nerve of erection.
 Characteristics of the sympathetic and parasympathetic
functions

• 1. The sympathetic functions are catabolic and energy consuming . They

increase the capacity of the body to do extra activities. In emergency or stress
conditions such as preparation of the body for fight , or flight , the sympathetic
system is strongly activated and discharges almost as a complete unit. This is
a phenomenon called mass discharge and it results in widespread sympathetic
effects throughout the body (sympathetic stress response) . The
parasympathetic functions are anabolic and energy preserving.

• The parasympathetic activity dominates during periods of emotional calm and

physical rest to control and regulate several discrete body functions e.g.
inhibition of cardiac activity to save energy during rest and stimulation of the
gastrointestinal secretions which favour digestion and absoption of food to
provide various tissues with nutrient materials for repair and storing energy.
• 2. the sympathetic and parasympathetic systems are continually active and the
basal rates of their stimulation are called sympathetic and parasympathetic
tone. These tones are not equal to the different organs e.g. the parasympathetic
tone is more dominant than the sympathetic to the gastrointestinal tract and to
the heart . On the other hand , the sympathetic tone is more dominant to the
blood vessels.

• 3. the sympathetic effects are usually generalized i.e. there is mass apathetic
discharge to many parts of the body at the same time as in stressful conditions.
On the other hand the parasympathetic effects are specific and localized.

• Sometimes , there may be association between closely related parasympathetic

functions e.g. salivary and gastric secretions usually occur at the same time .
Also urination and defaecation may occur at the same time.
 Central control of the autonomic functions

• 1. spinal cord

• The lateral horn cells of the spinal cord acts as lower autonomic centers.
Simple autonomic reflexes such as micturition and defection have their centers
in the sacral region of the spinal cord.

• 2. brain stem

• A) medulla oblongata contains centers that control the heart and

gastrointestinal tract.
• B) pons contains centers that control respiration
• C) midbrain contains centers that control the size of the pupils of the eye.
• 3. higher centers

• a) hypothalamus

• - stimulation of the anterior part causes parasympathetic actions.

• - stimulation of the posterior part causes sympathetic actions.
• - it is called the head ganglion of the autonomic nervous system because it is
the main brain center that controls complex autonomic reflexes . It also plays a
major role in stress conditions.

• b) cerebral cortex

• -certain areas in the cerebral cortex control the autonomic functions.

 Chemical transmission

• Transmission at the autonomic ganglia i.e. between pre and postganglionic

neurons and between the postganglionic neurons and the effectors and at the
motor end plate is carried by chemical substances . The most important
chemical transmitters are acetylcholine , epinephrine and norepinephrine.

• Other transmitters:

• - dopamine -- glutamic acid

• - serotonin --- enkephalins and endorphins
• -Histamine --- gamma amino butyric acid
• The neurons that secrete acetylcholine at their nerve endings are called
cholinergic , while the neurons that secrete norepinephrine are called
adrenergic ( or noradrenergic).

• Acetylcholine norepinephrine act on the different organs to cause sympathetic

or parasympathetic effects.

• These substances are called sympathetic parasympathetic mediators or

cholinergic or adrenergic mediators.
 Acetylcholine

• Site of release:

• Acetylcholine is released in the following sites:

• 1. all autonomic ganglia (sympathetic and parasympathetic)

• 2. adrenal medulla ( modified sympathetic ganglion)
• 3. skeletal muscle fibers at neuromuscular junction( these are called the central
cholinergic sites)
• 4. all postganglionic parasympathetic fibers
• 5. sweat glands and blood vessels of skeletal muscles innervated by
postganglionic cholinergic sympathetic fibers.( these are called the peripheral
cholinergic sites)
• 6. many parts of the brain.
• Nicotin – like action

• Small doses of nicotine produce the same effects as stimulation of the central
cholinergic fibers so the action of acetylcholine at these sites is called nicotine
like action of acetylcholine and the receptors are called nicotinic receptors.

• Muscarine – like action

• Muscarine also produces stimulation of the peripheral cholinergic fibers so the

action of acetylcholine at these sites is called muscarine like action and the
receptors are called muscarinic receptors.
 Synthesis and fate of acetylcholine

• Acetylcholine is continually synthesized in the terminal endings of

cholinergic nerve fibers
• choline
• Acetyl CoA + choline L acetylcholine
• acetyltransferase
• Once acetylcholine is secreted most of it is hydrolyzed into acetate
and choline by the enzyme choline esterase present in the tissues
supplied by cholinergic nerve fibers.
• The value of this enzyme is to keep the action of actylcholine
localized at the site of release and continue for a short time ,
otherwise it may diffuse to the blood causing generalized
parasympathetic effect.
 Cholinergic drugs

• They are drugs that produce the same action like acetylcholine.
• - it should be noticed that if acetylcholine is injected intravenously it will be
destroyed rapidly by choline esterases.

• Cholinergic drugs can be classified into two main groups:

• 1. choline esters : e.g. methacholine , carbachol …etc

• They produce the same action like acetylcholine and they are not destroyed by
cholinesterases

• 2. anticholine esterases
• These drugs act by inhibiting the action of cholinesterases . So they potentiate
the effect of the naturally secreted acetylcholine. They include:
1. reversible anticholine esterases
• 2. irreversible anticholine esterases
• a) reversible anticholine esterases:

• They combine temporary with choline esterase e.g. physostigmine (eserine)

and neostigmine (prostigmine) . Eserine acts more on the eye , so it is used in
the treatment of glaucoma (increased intra-ocular pressure ) to produce
constriction of the pupil . On the other hand , prostigmine acts more on the
neuromuscular junction (motor end plate ) so it is used in the treatment of
myathenia gravis.

• b) irreversible anticholine esterases

• They combine strongly and for a long time with choline esterases e.g. organic
phosphorus compounds as diisopropyl-flurophosphate (DFP) and the
insecticide parathion.
• These acetylcholine esterases especially irreversible , will lead to accumulation
of acetylcholine causing repetitive stimulation of the muscle fibers and results
in muscle spasm. This can cause death due to laryngeal spasm.
 Acetylcholine antagonists

• 1. Blockers of the central cholinergic receptors:

• a) ganglion blockers:

These are drugs that block the action of acetylcholine at all autonomic ganglia
( sympathetic and parasympathetic)

• i) competitive
• They compete with acetylcholine for the same receptors at the autonomic
ganglia e.g. tetraethylammonium ( TEA) and hexamethonium.

• ii) depolarization
• They produce initial stimulation of the autonomic ganglia due to depolarization
followed by blocking due to maintained depolarization e.g. nicotine.
• b) neuromuscular blockers:

• They block the action of acetylcholine at neuromuscular junction (motor end

plate

• i) competitive
• They compete with acetylcholine for the same receptor at the motor end plate
so they produce muscle relaxation e.g. curare

• ii) depolarizing
• They produce initial stimulation due to depolarization , then blocking of the
motor end plate due to maintained depolarization e.g. succinyl choline.
• 2. blockers of the peripheral cholinergic receptors

• They block the muscarine like action of acetylcholine . These drugs compete
with acetylcholine for the muscarinic receptors e.g. atropine.

• Atropine is used in the following conditions:

• 1. before surgical operations; atropine is given half an hour before general

anaesthesia to protect the heart from excessive vagal tone (bradycardia) and to
decrease salivary and bronchial secretions which may occur during
anaesthesia.
• 2. treatment of colics: atropine is used as antispasmodic to relieve smooth
muscle spasm in cases of intestinal , biliary , and renal colics.
• 3.it causes relaxation of the sphincter pupillae muscle leading to mydriasis
( pupillodilation) that helps in examination of the fundus of the eye i.e.
examination of the retina . Homatropine produces similar effects in the eye but
for a shorter time than atropine . Therefore , homatropine is preferred in eye
examination.
• 4. treatment of poisoning with anticholine esterases such as
organophosphorous compounds as DFP or insecticides as parathion.
 Norepinephrine

• It is the chemical transmitter at most sympathetic postganglionic nerve endings

and in some areas of the brain. It is stored in the synaptic knobs at the neurons
that secrete it. It is also secreted with epinephrine by the adrenal medulla.

• Synthesis and fate of catecholamines

• Catecholamines ( norepinephrine , epinephrine and dopamine) are formed by

hydroxylation and decarboxylation of the amino acids phenylalanine and
tyrosine.
• Following secretion of norepinephrine by adrenergic nerve endings, it is
removed from the secretory sites by:

• 1. reuptake into the adrenergic nerve endings by an active transport process

( 50-80%)

• 2. diffusion away from the nerve endings into the surrounding body fluids and
then into the blood (most of the remainder) . After that it is destroyed by the
enzymes monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)
. These enzymes are present in many tissues with high concentration as in
liver and kidneys.
 The adrenergic receptors

• There are two types of adrenergic receptors in the effector organs (alpha and
beta receptors), each is divided into two subtypes ( alpha 1 and alpha 2 ; beta 1
and beta 2). Epinephrine and norepinephrine act on both receptors, but
norepinephrine has greater affinity for x-receptors and epinephrine for p-
receptors.

• adrenergic stimulants

• 1. alpha receptors are stimulated mainly by nor epinephrine.

• 2. beta receptors are stimulated mainly by isoprenaline
3. alpha and beta receptors are stimulated by epinephrine.
 Adrenergic blockers

• 1. alpha receptors are blocked by phentolamine ( regitine)

• Beta receptors are blocked by propranolol ( inderal)
• Sympathetic autonomic ganglia are blocked by ganglion blockers as
hexamethonium.
• Synthesis of norepinephrine can be blocked by metyrosine demser
• Interference with norepinephrine storage by reserpine (serpasil)
• Prevention of norepinephrine release by guanethidine (ismelin)
• Form false transmitters as methyldopa ( aldomet)
 Summary of adrenergic stimulants and blockers

Site of action Stimulation inhibition

Alpha-receptors norepinephrine phentoamine

Beta-receptors Isoprenoline Propranolol (inderal)

Alpha and beta receptors Epinephrine -

Sympathetic autonomic Diluted nicotine hexamethonium

ganglia
Norepinephrine synthesis - Metyrosine (demser)

Norepinephrine storage - Reserpine (serpasil)

Norepinephrine release - guanethidine (ismelin)

Form false transmitter - Methyldopa (aldomet)

 Adrenal medulla

• It is modified sympathetic ganglion in which the pre-ganglionic sympathetic

fibers pass without synapting through the sympathetic chain to the adrenal
medulla. Stimulation of the sympathetic supply to the adrenal medulla causes
the release of large amounts of hormones (80% epinephrine and 20%
norepinephrine) into the circulation.

• Usually when any part of the sympathetic nervous system is stimulated, major
parts of the entire system are stimulated at the same time . Also epinephrine
and norepinephrine are secreted by the adrenal medulla . Subsequently , the
organs are stimulated by two ways at the same time which support each other.
•
• a) directly by the sympathetic fibers.

• b) indirectly by the adrenal medullary hormones (more prolonged action)

through the blood supply.
 Myasthenia gravis

• It is a serious and sometimes fatal disease in which the skeletal weak and tire
easily. It is caused by the formation of circulating antibodies to the nicotinic
acetylcholine receptors, which destroy some of these receptors . In the severe
cases, the patient may die due to paralysis of the respiratory muscles.
Myasthenia gravis is treated by neostigmine (reversible anticholine esterase) .
This drug prevents destruction of acetylcholine secreted by the motor end plate
, so its quantity increases until it can stimulate the muscle.