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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



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Organization of the nervous system

Nervous systemNervous system

Central NSCentral NS Peripheral NSPeripheral NS

Autonomic NSAutonomic NS Somatic NSSomatic NS

Sympathetic NSSympathetic NS Parasympathetic NSParasympathetic NS



5

Somatic pathwaySomatic pathway

AHC



6

LHC



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 theflexor muscles and inhibition of the extensor muscles e.g. pin prick to the skinleads to sudden withdrawal of the limb.

2. autonomic reflex arc

The autonomic reflex arc differs from the somatic reflex arc mainly in that ithas two efferent neurons.



Diff erences between somatic and autonomic

reflex arcs

Somatic reflex arc Autonomic reflex arc

The receptor Usually in the skin Usually in a viscus

The afferent

neuron

Passes via a dorsal root or

cranial nerve and has its cell

body in the dorsal root ganglion.

The same like the somatic reflex arc

The center The anterior horn cell The lateral horn cell

The efferent

neuron

It is composed of one neuron

only

It is composed of two neurons . It passes

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 axonsof 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

Th

ey lie betw

een th

e sympath

etic ch

ain and th

e viscera.Th

ey lie at th

e origin of bigarteries. 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 activatesmany 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 activatesfew postganglionic neurons.This distribution produces localized

parasympathetic effects.



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Autonomic ganglia It is a collection of neurons

outside the CNS.

Itis the s

ite o

f synapsebetween the preganglionic

and the postganglionic

neurons.

It act as a distributingcenter.



2006-200718

Lateral and collateral gangliaLateral and collateral ganglia



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Parasympathet

ic NSParasympathetic NS

is character

ized by:

is character

ized by:*The*The preganglionicpreganglionic fibers synapse in thefibers synapse in the

terminal terminal gangliaganglia..

**LongLong preganglionicpreganglionic fibers.fibers.

*The postganglionic eff ects are mediated*The postganglionic eff ects are mediatedthroughthrough acetyl acetyl cholinecholine..



2 nd year Phamacy (2006-2007) 20

Sympathetic NS

Sympathetic division

of the ANS is called

the fight and flightdivision.

It prepare the body to

deal with stress.



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Parasympathetic NS

Parasympathet

ic NS is called

the rest andsleep division

of the ANS.

It allows the

body torecover f rom

stress



Sympathetic nervous system

Thoracolumber:

It consists of two neurons, pre and post ganglionic . Thepreganglionic 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.



Eff ects of stimulation of the sympathetic ner vous system

Organ Eff ects

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

-Heart

-lungs

Stimulation of all properties of the heart:

-increased heart rate.

-increased force of contraction.

-dilation of the coronary vessels.

-dilation of the bronchi.

-slight constriction of the pulmonary vessels.

Abdomen

-Liver

-Stomach and intestine

-Gall bladder and bile

ducts

-Adrenal medulla

Constriction of the blood vessels of the viscera.

Stimulation of glycogenolysis ( increase in blood glucose

level).

-decreased motility and decreased secretion

Increase in tone of sphincters i.e. contraction of sphincters..

-relaxation of the wall and contraction of sphincter.

-stimulation of epineph

rine and norepineph

rine secretion.



CONTINU.SYMPATHETIC

f unct

ions

pelvis

-Constriction of the blood vessels of the viscera.

-inhibitory to the wall of the urinary bladder , motor to the sphincter

causing retention of urine.

-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

and abdominal

walls.

-constriction of the skin blood vessels.

-dilation to the muscle blood vessels.

-excess secretion of sweat glands.

-contraction of piloerector muscles.

-skeletal muscles glycogenolysis , increased strength of

contraction

General effects

- Increased mental activity

- 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 haemorr hage.



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 tovital organs and muscles.

4. dilation of the bronchi causing better lung ventilation

5. constriction of the blood vessels of the skin , gut, kidneysand spleen i.e. shift of blood from unimportant organs toimportant 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 adrenalmedulla. 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

effects

Oculomotor nerve {third

cranial nerve } (III )

-motor to sphincter pupillae muscle leading to

constriction of the eye pupils.

-motor to the ciliary muscle causing accomodation for

near vision.

Facial nerve {seventh

cranial nerve} ( VII )

-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.

Glossopharyngeal nerve

{ninth cranial nerve} (IX )

-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

cranial nerve} ( X )

Heart

Lungs

-Inh

ibition to all properties of th

eh

eart.--constriction to the coronary blood vessels.

-Bronchoconstriction.

-Dilation to the bronchial blood vessels.

-Increases mucus secretion in the respiratory air passages.

GIT

-stimulation of peristalsis of the esophagus, stomach , small

intestine and proximal half of the large intestine i.e. increasedmotility.

-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 autonomicnerve { second , third

and fourth sacral

segments }

-contraction of the muscle of the urinary bladder and relaxation of its sphincter causing micturation.

-contraction of the distal half of the large intestine and rectum and

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 . Theyincrease the capacity of the body to do extra activities. In emergency or stressconditions such as preparation of the body for fight , or flight , the sympatheticsystem is strongly activated and discharges almost as a complete unit. This isa phenomenon called mass discharge and it results in widespread sympatheticeffects throughout the body (sympathetic stress response) . The

parasympath

etic functions are anabolic and energy preserving.

The parasympathetic activity dominates during periods of emotional calm andphysical rest to control and regulate several discrete body functions e.g.inhibition of cardiac activity to save energy during rest and stimulation of thegastrointestinal secretions which favour digestion and absoption of food to

provide various tissuesw

ith

nutrient materials for repair and storing energy.



2. the sympathetic and parasympathetic systems are continually active and thebasal rates of their stimulation are called sympathetic and parasympathetictone. These tones are not equal to the different organs e.g. theparasympathetic tone is more dominant than the sympathetic to thegastrointestinal tract and to the heart . On the other hand , the sympathetictone is more dominant to the blood vessels.

3. the sympathetic effects are usually generalized i.e. there is mass apatheticdischarge to many parts of the body at the same time as in stressfulconditions.On the other hand the parasympathetic effects are specific andlocalized.

Sometimes , there may be association between closely related parasympatheticfunctions e.g. salivary and gastric secretions usually occur at the same time .Also urination and defaecation may occur at the same time.



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 parasympath

etic 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 ner ve fibers

choline

Acetyl CoA + choline L acetylcholine

acetyltransf erase 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 ner ve fibers.

The value of this enzyme is to keep the action of actylcholine

localized at the site of release and continue f or a short time ,otherwise it may diff use to the blood causing generalized

parasympathetic eff ect.



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 potentiatethe 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 inthe treatment of glaucoma (increased intra-ocular pressure ) to produceconstriction 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. organicphosphorus 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 resultsin 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.



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)

Alph

a and beta receptors Epineph

rine -

Sympathetic autonomic

ganglia

Diluted nicotine hexamethonium

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 sympatheticfibers pass without synapting through the sympathetic chain to the adrenalmedulla. Stimulation of the sympathetic supply to the adrenal medulla causesthe 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 epinephrineand norepinephrine are secreted by the adrenal medulla . Subsequently , theorgans 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.

new autonomic nervous system dr

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