Lecture 5, Autonomic Nervous system (Script)

8/3/2019 Lecture 5, Autonomic Nervous system (Script)

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3/10/2011 **Autonomic Nervous system(ANS)*lecture #5

*You can refer to the book and this lecture is from chapter 3 (The ANS)at

the beginning of the lecture the Dr was arguing a student that he wouldnt

give us the lectures(hands out) anymore, and I have no idea if that is true.

*In previous lectures we discussed General Pharmacology and we discussedRoutes of Drug Administration, Pharmacokinetics and Pharmacodynamics.*Today we will discuss the Systemic Pharmacology, we will discuss drugs

which act on the autonomic nervous system and before that we are going to

talk about the physiological aspect and anatomical aspect of the ANS and thephysiological aspect of each group of the drugs from the point of view of

mechanism of action, therapeutic uses, side effects, toxicity and

contraindication .

Contraindication: conditions where we shouldnt use the drug in, it is use could

be harmful or some kind might be dangerous. ( ,

, )

Therapeutic uses: diseases which could be treated by these individual drugs.


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*DIFINATION OF ANS:The major involuntary, unconscious, automatic portion of the nervoussystem; which include two major sections: sympathetic and

parasympathetic1)Sympathetic system : Since it is originated from the thoracolumbarregion

(T1 to T12 and L1 to L5) so it is called thoracolumbar system but

commonly called sympathetic.2)Parasympathetic system: since it is originated from cranial nervesnumber III, VII, IX and X and from the sacral spinal segments (S2 to

S4) so it is called craianiosacral

* Here we have a simplified diagram for the Autonomic Nervous System(you can find the figure in the hands out) and he start explaining the

figure..and from the figure :


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-This is central nervous system is the brain and the spinal cord and these

are the autonomic nerves ..

*And you can see that autonomic nerves are composed of two types of

nerve fibers:

The preganglionic nerves and postganglionic nerves.

Preganglionic neuron: the neuron before the ganglia. It originates fromCNS and ends in the autonomic ganglia.

Postganglionic neuron: the neuron after the ganglia. It originates in theganglia and ends in the effector organ.

*Now the difference between the preganglionic and the postganglionic

nerve fibers in sympathetic and parasympathetic:

1) Sympathetic system:


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-postganglionic nerves (too long) are longer than preganglionic nerves(too

short), why??

Answer: because the ganglia are away from the effector organ.

-Postganglionic neurons in the sympathetic system supply sweet glands,

cardiac smooth muscles, other glands, renal blood vessels and smooth

muscles.

-Preganglionic here supply the adrenal gland to secret into the blood

epinephrine and norepinephrine.

2) Parasympathetic system:-preganglionic nerve fibers are longer than postganglionic nerve fibers,

why??

Answer: because the ganglia is embedded in the effector organ.

-Postganglionic nerve endings in parasympathetic system supply the heart,

the smooth muscles and the glands.

-The lowest nerve in the figure in the hands outs figure is apreganglionic(because it is originated from the central nervous system from the spinal

cord) parasympathetic neuron ( because it is of long length , longer of thepreganglionic nerve of the sympathetic supplying the skeletal muscles.)

*The Dr. read a paragraph from the hands out about the

Neurotransmitter:

Stimulation of a nerve releases (not sure) a substance at the nerve ending

which activates receptors in the organ that will be supplied or in other


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nerve.These substances which activate organ or nerve after they are

secreted called neurotransmitters

Neurotransmitter (NT)( ):in other words :

A chemical substance released in the synapse after nervous stimulation to

carry nerve impulse from one neuron to the other or from one neuron to

the effector organ

**All NT in the autonomic ganglion either sympathetic or

parasympathetic is acetylcholine **

*Neurotransmitters is called so because they transmit nerve impulses

through neurons.

*The difference between the NT of sympathetic and parasympathetic

nervous system:

At the end of each neuron and the beginning of the next neuron, there is a

gap, this gap is called the synapse.

Also there is another gap between the postganglionic neuron and theeffector organ is called synapse.


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1)sympathetic system:-The neurotransmitter in the postganglionic nerve endings of this one is

epinephrine or norepinephrine (in some books it might be written

adrenaline and noradrenaline)

2) parasympathetic system:-Nerve endings or postganglionic neurons of this system the transmitter is

Acetylcholine*The dr. again start discussing the diagram

In the hands out(the dr is repeating theLast few notes quickly) :(this is a diagram showing the

Postganglionic and the Preganglionic

Neurons of theparasympathetic nervous system,, this is the ganglion andthe NT is acetylcholine, and this is the effector organ whether the smooth

muscles,skeletal muscles or glands the NT again is acetylcholine.

On the other hand the sympathetic nervous system you can see thepreganglionic neurons is short, the postganglionic is long, the NT in the

ganglia is acetylcholine and the NT in the effector organ is epinephrine or

norepinephrine except the sweat gland it is supplied by acetylcholine)

*The effect of the neurotransmitter acetylcholine in the parasympathetic

ganglia and sympathetic ganglia could be blocked by a drug calledganglion blocker*The effect of acetylcholine on the effector organ could be blocked by a

drug called cholinergic blockers or anti-cholinergic blockers! !

EPINEPHRINE = ADRENALINE

EXCEPTION! :

In sweat glands are supplied by sympathetic

postganglionic neurons ,despite that the NT isAcetylcholine and NOT epinephrine or

norepinephrine


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-why cholinergic ?? because it is transmitted by acetylcholine ,,

-ACETYLCHOLINE is composed of acetyl & choline so it is acetylated

choline

**Termination:*For proper transmission, the released NT effect has to be terminated, if

it is not terminated after producing effect, the effector organ automatically

will be exhausted and tired and later on it will be nonfunctional (if there is

continues ????? didnt hear it but I guess it is indication or induction

not sure), therefor the effect of the released NT after producing specific

effect has to be terminated.

*How the effect of the released acetylcholine could be terminated???It will be terminated by enzymatic reaction; the acetylcholine will be

hydrolyzed an enzyme called cholinesterase or acetyl cholinesterase

(esterase = an enzyme, this is the enzyme which is responsible foresterification of the substance)

By this enzyme; acetylcholine is splitted into acetyl group (the dr said itonce as acetate group and once as acetyl group) and choline group underthe effect of this enzyme, now acetylcholine is inactivated so its effect is

terminated.

-cholinesterase could be inhibited by a drug called anti-cholinesterase*Now what about the sympathetic nervous system??-The receptor in the effector organ (which accept the NT of thesympathetic) ,as u know from physiology course, receptors could be;

Alpha or Beta.

-here we have the NT is epinephrine or norepinephrine ,and we have

receptors of types; alpha 1 & alpha 2, beta 1 & beta 2..again the effect of

Remember; cholinergic termination is

done by the enzymatic effect of the


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the NT at the sympathetic nerve endings also should be terminated for

proper function of the released NT ,,and the postganglionic sympathetic

nerve endings the NT effect has to be terminated.

-here in sympathetic transmission the main process of

Termination of the effect is not an enzymatic react

although a minor process is by enzymatic reaction but the main process of

the termination of effect is called Active Reuptake mechanism. Thismeans that the released norepinephrine will be actively taken up back to

the terminal end (the side where the NT was released from ) of thesynapse and is called again for further used. So active reuptake is the main

process of termination in the sympathetic nervous system. Other

termination mechanism is an Enzymatic Depredation of these NT byenzymes called MAO (monoamine oxidase)epinephrine andnorepinephrine they are monoamine and they are oxidized by the

enzyme MAO to terminate its effect , and COMT (catechol-o-aminetransferase) also NT are catechol ,, HW!! What is catechol????

*The function of the 2 types of the autonomic nervous system ..The dr explaining a table should in the hands out : this table shows you

the types of cholinergic receptors and their location and the response

produced by stimulation of these receptors; we have what we called

Muscarinic receptors and Nicotinic receptor , muscarinic receptors arethose receptors which are found in some autonomic ganglion; the heart,

in smooth muscles of the GIT, of the respiratory system, of the urinary

tract and the gland in these systems (like salivary glands in GIT) and other

glands like sweat glands.


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The Nicotinic receptors are found in the neuromuscular junction in theskeletal muscle, in some autonomic ganglion and in the adrenal medulla.

-Response of Stimulation of these locations in the autonomic ganglion

there is is deep polarization and fever (sure at all from the word but youcan find it in the table in the hands out),, in the heart; decrease in the

heart rate and force of contraction Smooth muscles contraction and

secretion of the glands (which are supplied by cholinergic neurons) both

will

be increase,,

e.g : contraction of the smooth muscles wilproduce bronchoconstriction(constriction of the smooth muscle of the bronchi) .*next table in the hands out is about the types of adrenergic receptors and

their Location (alpha 1 & 2, beta 1&2 )the dr read the table ..

Important termes :

*Decrease in heart rate is called bradycardia

*Increase in heart rate is called tachycardia

The contraction of smooth muscles on intestine is called intestinal

contraction and of the ureter is called ureteric contraction and so on..


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Alpha 1 supplied smooth muscle, vascular and Genitourinary, intestinal

and liver.

The effect of stimulation alpha 1 receptor on :

vascular blood vessel or smooth muscle is contraction That production

of whats called vasoconstriction while relaxation of smooth muscle iscalled vasodilatation.

On bronchi, bronchoconstriction for contraction and broncho -

dilatation for relaxation

On Genitourinary is contraction.

On intestinal is relaxation.

On the liver the stimulation of alpha 1 receptor will stimulate

Glycogenolysis and gluconeogenesis.-Glycogenolysis: the split of glycogen into monosaccharide and into

glucose.

-Gluconeogenesis for mention of glucose from other sources other than

the carbohydrate.


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Alpha 2 stimulation :1- decrease norepinephrine release that have inhibition receptor

2-On the platles produce platlets aggregation.

3- beta-cells of Pancreas decrease insulin release which will decrease

blood glucose level!

4- On Vascular smooth muscle Produces contraction

Effect on beta 1 on the heart increase the heart rate and the force of

contraction that will be tachycardia and increase force of contraction and

On juxtaglomerular cells Increase renin release

5- smooth muscle ,vascular, genitourinary , intestinal and bronchial all

these smooth muscle wil be relaxed by stimulation of beta 2 receptor.

6- On skeletal muscle increase contractility and Glycogenolysis while

stimulation of nicotinic cholinergic muscle will produce skeletal muscle

contraction or relaxation ? please answer tht

7- Beta cells of pancreas increase insulin secretion while effect on alpha 2

lead to dencrease insulin secretion.

To summarize all these effects systematically :

Stimulation of sympathetic nervous system on the CVS, the heart rate and thecontractility the BP will be increases.

While the stimulation of Parasympathetic nervous system will decrease all

these!

smooth muscle bronchi, GI tract motility will be relaxed be sympathetic


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nervous system, contracted by parasympathetic nervous system

stimulation.

The sphincter will be contracted by sympathetic nervous system and

relaxed by parasympathetic nervous system, for example; the bladder is

balloon shaped with an orifice the balloon is called the body of the

bladder and orifice is called urethral sphincter. Parasympathetic

stimulation lead to the contraction of the body plus relaxation of sphincter

if both are contracted the bladder subsequently will be rupture because

the aim of bladder body contraction is void urine and voiding urine the

sphincter should be relaxed and the body should be contracted the other

way is true after sympathetic stimulation; the sphincter will be contracted

and the body of bladder will be relaxed! and the same for the stomach so

the body of vicious organ will be contracted and its sphincter will be

relaxed in parasympathetic stimulation and vice versa or the reverse is true

as regard of sympathetic stimulation.

ureter smooth muscle relaxed by sympathetic stimulation and contracted

by parasympathetic stimulation.

secretion of salivary gland increased by sympathetic and parasympatheticstimulation! but the deference between them is in the quality of secretion;

being thick mucous in case of sympathetic stimulation and watery in case

of parasympathetic stimulation.

gastric and intestinal secretion and bronchial secretion both decreased

after sympathetic stimulation and increased after parasympathetic

stimulation.

about the eye, the pupil will be dilated" mydriasis" by sympatheticstimulation, while after parasympathetic stimulation there'll be constriction

or miosis so drugs which can produce mydriasis on the pupil they are

called mydriatic drugs and drugs which can produce miosis they are called

miotic drugs.


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on the ciliary muscles there's no effect of sympathetic stimulation because

they're not supplied by sympathetic neurons while ciliary muscle will be

contracted after parasympathetic stimulation, lastly metabolic action there

will be after sympathetic stimulation and there's no effect of

parasympathetic stimulation>

on sex organ officially in the male, sympathetic stimulation aid in the

ejaculation while parasympathetic stimulation aid in erection process.

Drugs :Sympathomimetic (Mimetic means similarities) or sympathetic drugs :

drugs which have an effect similar to sympathetic stimulation; drugs that

have effect similar to increase sympathetic effect.

adrenaline : is the prototype of this group , its an acid labile and its not effective orally cause its rapidly

metabolized in the GI tract and liver , and to be useful therapeutically it

has to be given by injection or by parenteral route of drug administration

therefor its either given subcutaneously or intramuscularly and sometimes

rare times intravenously.

Onset of action after subcutaneous or IM is ???? takes only one minute

but after IV injection itll be immediate!

The effect of adrenaline we can concloud it from sympathetic stimulation

effect.

Adrenaline injection can increase the heart rate producing tachycardia,

increase force of contraction of heart leading to palpitation )

awareness of heartbeat); when theres increase in both rate and force of

contraction, the patient might feel the beats of his heart.


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About the blood pressure, therell be increase in systolic blood pressurebut little change in diastolic blood pressure.

on smooth muscle therell be smooth muscle bronchial relaxation. Andsmooth muscle relaxation in any part of the body GI tract smoothmuscle relaxation, urinary tract smooth muscle relaxation .

Adrenaline: Raises blood sugar glucose levels hyperglycemia andthe decrease in blood glucose levels called hypoglycemia.

The effect of adrenaline lasts only for a few minutes because of rapid

metabolisms by enzymes MAO and COMT.

adrenaline therapeutic useful uses :1-Treat cardiac arrest or complete heart block, to stimulate the heart

muscle to beat forcibly or to stimulate the conductive process

between the heart champers, in heart block theres a delay in the

conduction between the atria and ventricle , this delay will be

corrected by given adrenaline.

2- to control local bleeding after dental surgery3-To treat epistaxis / nasal bleeding

In case 2 and 3 above to stop the bleeding they take a piece of

cotton wool soak it with adrenaline solution and put inside one of the

nostrils bleeding nostrils or ask the patient to bite this piece in case

of bleeding after dental surgery.

Why adrenaline can control this type of bleeding

Because it can cause sever basal constriction and this will

reduce/limit the bleeding.

4-To treat the prolong the action of local anesthesia; most therapeutic

dental procedures are painful so they should be performed under


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local anesthesia, and local anesthesia might be of two type plain or

mixed with a vasoconstrictor, the vasoconstrictor here is either

adrenaline or noradrenaline.

Whats the idea behind mixing these local anesthesia withvasoconstrictor

to prolong the duration of their action, to delay the rate of their

removal in the site o action.

5-To treat hypotension, why because adrenaline can increase the

systolic blood pressure.

6-Treatment of bronchial asthma its bronchial constriction, why

adrenaline can produce bronchial dilatation so it will treat acute

attack of the bronchial asthma, in this case it should be given SC.

7-Treatment of anaphylactic shock; its severe hypersensivity reaction

and the common example is hypersensivity reaction after taken

penicillin penicillin on some patients can produce a severe

hypersensivity reaction, that means antigen reacts antibody lead to

release of large amount of histamine and histamine can lead to

generalized vasodilation and severe bronchial constriction. These 2

effects might be fetal if they are not treated urgently.

Treatment : give adrenaline; adrenaline can produce the opposite

effect of these dangerous effects so it can produce generalized

vasoconstriction and potent bronchodilator effect.

8-Treatment of glaucoma ( a painful condition

in the eye due to rise in intra-occuler pressure IOP and the eye of

this case is full of fluid aqueous humour which is between the

eye lens and the cornea). The pressure in this aqueous humour or

anterior chamber of the eye is intra-occuler pressure, in some

conditions this IOP is increased leading to severe pain in the eye


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ball and if not treated might lead to blindness and adrenaline can

reduce elevated IOP.

The side effects of adrenaline :I. Cardiac arrhythmia ( disturbance in a heart rate or rhythm ) or

palpitation.

II. Hypertension, it rise in severe ???? in systolic blood pressure which

might be complicated by cerebral hemorrhage ( intracranial

bleeding ).

III. To treat precipitation of angina pectoris severe chest pain in the

anterior aspect of a chest wall might be projected to the left arm orthe lower jaw this is due to mental or physical overload on the heart

.

IV. CNS side effects:

1-reslessness.

2-tremor is a type of shakingmovement. A tremor is most oftennoticed in your handsand arms.

3- Insomnia .. is inability to sleep to start or complete sleep

4-Anxiety .

Contraindications:Conditions we can NOT use adrenaline .

Hypertension.

Hyperthyroidism hyper function of thyroid gland , which is

manifested usually by hypertension, hyperglycemia, tachycardia andsometimes arrhythmia and palpitation.

Congestive heart failure, we cant use it here cause itll increase

the load on the heart.


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Diabetes mellitus, why because adrenaline can aggregate the

hyperglycemia of diabetes.

The end..

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!"

!!

* "One kind word can warm three winter months." --Japanese Proverb.

John F. Kennedy said, "the courage of life is a magnificent mixture of triumph and tragedy.

A man does what he must, in spite of personal consequences, in spite of obstacles and

dangers and pressures. And that is the basis of all morality"

There comes a time when every life goes off course. In this desperate moment you must

choose your direction. Will you fight to stay on the path while others tell you who you are?Or will you label yourself? Will you be honored by your choice? Or will you embrace your

new path? Each morning you choose to move forward or to simply give up .


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*Big big big big thx to Raghas Khasawneh for her help wallah ma

gasarat kan saebne malal syndrome n she deal with that.. .. allah

yejzaki el5air o ya36eke ele fe balik

Done by Difaf Khuwaileh..

Lecture 5, Autonomic Nervous system (Script)

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