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 discussed
Routes 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 the
physiological 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.

*DIFINATION OF ANS:
The major involuntary, unconscious, automatic portion of the nervous
system; which include two major sections: sympathetic and
parasympathetic
1)Sympathetic system : Since it is originated from the thoracolumbar
region
(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 nerves
number 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 :

-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 from
CNS and ends in the autonomic ganglia.
Postganglionic neuron: the neuron after the ganglia. It originates in the
ganglia and ends in the effector organ.
*Now the difference between the preganglionic and the postganglionic
nerve fibers in sympathetic and parasympathetic:
1) Sympathetic system:
-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 a preganglionic
(because it is originated from the central nervous system from the spinal
cord) parasympathetic neuron ( because it is of long length , longer of the
preganglionic 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
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 the
effector organ is called synapse.
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 the
Last few notes quickly) :
(this is a diagram showing the
Postganglionic and the Preganglionic
Neurons of the parasympathetic nervous system,, this is the ganglion and
the 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 the
preganglionic 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 called
ganglion 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 is
Acetylcholine and NOT epinephrine or
norepinephrine
-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 for
esterification of the substance)
By this enzyme; acetylcholine is splitted into acetyl group (the dr said it
once as acetate group and once as acetyl group) and choline group under
the 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 the
sympathetic) ,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
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. This
means that the released norepinephrine will be actively taken up back to
the terminal end (the side where the NT was released from ) of the
synapse 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 by
enzymes called MAO (monoamine oxidase)epinephrine and
norepinephrine they are monoamine and they are oxidized by the
enzyme MAO to terminate its effect , and COMT (catechol-o-amine
transferase) 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 are
those 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.
The Nicotinic receptors are found in the neuromuscular junction in the
skeletal 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 you
can 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..


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 is
called 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.

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 the
contractility 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
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 parasympathetic
stimulation! 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 sympathetic
stimulation, 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.
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.
About the blood pressure, therell be increase in systolic blood pressure
but little change in diastolic blood pressure.
on smooth muscle therell be smooth muscle bronchial relaxation. And
smooth muscle relaxation in any part of the body GI tract smooth
muscle relaxation, urinary tract smooth muscle relaxation .
Adrenaline: Raises blood sugar glucose levels hyperglycemia and
the 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 surgery
3- 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
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 with
vasoconstrictor
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
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 or
the 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 shaking movement. A tremor is most often
noticed in your hands and arms.
3- Insomnia is inability to sleep to start or complete sleep ..
4- Anxiety .
Contraindications:
CConditions we can NOT use adrenaline .
C Hypertension.
C Hyperthyroidism hyper function of thyroid gland , which is
manifested usually by hypertension, hyperglycemia, tachycardia and
sometimes arrhythmia and palpitation.
C Congestive heart failure, we cant use it here cause itll increase
the load on the heart.
C 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 .
*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..