Autonomic Nervous System (General Visceral Efferent System)

Autonomic Nervous system supplies all the smooth muscles in the body,
glandular structures and the myocardium.
Is a motor system predominantly and controls involuntary movements in
the body.
ANS innverates all innervated structures in the body except the NMJ of
skeletal muscles.
Anatomical divisions of ANS: Sympathetic (under flight-or-fight stresses
are activated), Parasympathetic (Rest & digest), Enteric Nervous system
(myenteric, Auerbachs plexus ) (ENS nerves= nerves of spinal cord)

Sympathetic Nervous System

Hypothalamus is made up of two parts with 2

divisions: Anteromedial (concerned with
parasympathetic activity) and Posterolateral parts
(concerned with sympathetic activity).
Major regulator of hypothalamus is limbic system.
Limbic system is concerned with emotional
behavior, short-term memory, smell and primitive
behaviors (survival, preservation, perpetuation)
Steps:
1. Auditory cortex is stimulated by
receiving info of a dog barking
and recognizes as an unfriendly
sound
2. These give impulses to the fear
center in the limbic system
3. There is visual info of a dog
running to him and is received by
as a hostile image in the visual
cortex.
4. It sends signals to the fear center
in the limbic system.
5. Memory centers from the parietal
lobe trigger the limbic system as
well.
6. Unpleasant thought processes will
be sent from the frontal cortex to
the limbic system.
7. If the dog bites there will be
ascending information of pain and
touch to the limbic system.
8. Limbic system will be receiving
info from all parts of the body it will analyze the info to figure out if the
info is good/bad. Ultimately leading to fear in this situation.
9. Limbic system will send information to the and alter sympathetic and
parasympathetic activity sections of the hypothalamus

10.
Neurons that are going the Parasympathetic are inhibitory and
Sympathetic are excitatory.
11.
There are
polysynaptic pathways
that are descending
from the sections from
the hypothalamus that
take the info -> reticular
formation -> tractus
solitaris structures will
modify the info that
goes into the spinal
cord.
12.
The spinal cord is
divided into cervical,
thoracic, lumbar and
sacral. As the pathways
descend they will not
stimulate any fibers
from the brainstem and
cervical section of spinal cord.
13.
They will stimulate
preganglionic sympathetic fibers
outgoing from thoracic segments
(T1-T12) and lumbar segments
(L1 and L2). This is called
thoracolumbar outflow.
14. These preganglionic fibers send
info the sympathetic ganglion;
some terminate at this
location(1)/ it will go to ganglion
at upper level of exit(2)/ go to a
ganglion at a lower level of
exit(3)/ go from ganglion to
prevertebral ganglion
(superior/inferior mesenteric
ganglion)(4)/ganglion to adrenal medulla to release epinephrine (5)
15.
From these ganglions it went to there are postganglion fibers
that go from there
Polysynaptic descending tracts of the spinal cord stimulate interomedial
lateral horns of the spinal cord that have cell bodies.
These cells will have fibers that go out bilaterally as preganglionic
sympathetic fibers from the thoracolumbar cord.

From the lateral horn preganglionic fibers go out into the ventral root, and
from there they jump to the sympathetic chain ganglion via the white
rami communicans (myelinated)
Some fibers have the 1-5 pathways mentioned above
All the neurons that come out of the CNS (innvervating PNS, SNS and
NMJ) are motor and cholinergic neurons
Preganglionic fibers are cholinergic neurons that release Ach on the
sympathetic ganglion chain/cell bodies of postganglionic neurons/
interneurons
Interneurons are present within the ganglion and are dopaminergic
Postganglionic fibers will jump to the closest associated spinal nerve and
this pathway is gray rami communicans (unmyelinated) and can be found
all along the spinal cord
The spinal nerves will go either into the ventral/dorsal rami
They will finally end up innervating the limbs or the
anterolateral/posterolateral body walls
They supply the vasculature of limbs, body walls, skin sweat glands, pilli
erector muscles, visceral
organs
How do the sympathetic
fibers innervate the
viscera? Some of the
sympathetic fibers will
enter the ganglion and
dont terminate there and
just exits there and are still
preganglionic and go to the
ganglions close to the
viscera called the
prevertebral ganglion.
Sympathetic ganglion are
present along the sides of
the vertebral column
Prevertebral ganglion
(cliac, superior mesenteric,
inferior mesenteric
ganglion) do not make a
chain like paravertebral
ganglion and these fibers go around blood vessels
T1-T5 segments will supply the heart with fibers that ascend upward to
sympathetic celiac ganglion and will become cardiac nerves
Many sympathetic ganglions put together make up the adrenal medulla
with only incoming preganglionic fibers activating it and they pour out
their horomones; epinephrine and NE via the general blood circulation.
The heart can be triggered either by the post ganglionic nerves that
release adrenergic hormones there/ hormones released by the adrenal
medulla

NE outflow from postganglionic fibers while epinephrine come fromt eh

ciculation

Increased
Increased
Sympathetic
Sympathetic
activity
activity

NE
NE &&
Epinephrine
Epinephrine
release
release

Stimulated
Stimulated

Inhibited
Inhibited

All
tissues
because
All tisues
tisues have
have Alpha1
Alpha1 AR
AR except
except these
theseTissues
tissueshave
because they
they have
have B1
B1 receptors:
receptors:
Tissues
have
Heart
Heart
Alpha
B1
A2
Alpha 11
B1 Adrenergic
Adrenergic
A2 Adrenergic
Adrenergic
JGA
JGA in
in kidney
kidney
Adrenergic
Receptors
receptors
Adrenergic
Receptors
receptors
Adipocytes
Adipocytes
Receptors
Receptors

B2
Adrenergic
B2 Adrenergic
receptors
receptors

Sympathetic Effects on Organ Systems

Arrector pilli muscles are innervated by the A1 adrengic receptors during

fight-flight response
There are radial muscles that contract to pull the pupil outward resulting
in pupillary dilation and these are innervated by the a1-adrengergic
receptors
Caudate nucleus has many automatic motor programs stored.
Atropine is used as eye drops and they dilate the pupils and they are used
by women to make their eyes look more attractive, but a side effect is
cycloplegia
Eyeball has a muscle called cilaris and the lens which have their ends
attached to suspensory ligaments
o When ciliaris contracts the anterior end is fixed-> the posterior
end will move forward and inward-> the zonules become loose and
lens become globular

When
ciliary
muscle
contracts
the lens
move

o Under fight-flight response the lens have to flattened to be able to

see far visions, and in order for that to occur the ciliaris has to
When ciliary
muscle
be relaxed instead of contracted
relaxes the
lens move
o B2 adrenergic receptors have to be stimulated, the inhibitory
backwards
receptors of the sympathetic NS
Under stress there skin should receive little blood supply as it does have
no role in fighting-> underperfusion of the skin
The skin should have constricted cutaneous vasoconstriction that means
the smooth muscles are stimulated by their a1 adrenergic receptors
Increased respiratory rate with the adrenergic system stimulating the
respiratory centers
In the lungs the bronchi should be
dilated because during there is more
need of oxygen and more C02 to
expel
When the a1 AR (bronchi blood
vessels) are stimulated there is
decreased blood flow to the
bronchioles because of the
vasoconstriction of blood vessels->
decreased interstitial fluid ->
decreased swelling of mucosa->
decreased airway secretions
There are increased mast cells in the
bronchi and they have to be
inhibited, so B2 AR because if they release histamine can be a problem
The bronchiolar smooth muscles cells have to be relaxed so they have b2
AR so the sympathetic NS is inhibited there so the airway is relaxed
During stress most of the blood flow is diverted from the other organs
such as kidney, skin, GiT because the skeletal muscles need it more under
the flight-or-fight response
So these various organs under sympathetic activity have their a1 AR
activated to ensure vasoconstriction, but skeletal mucle cells need
excessive blood flow so under sympathetic activity inhibitory B2 AR are
activated for vasodilation
Sympathetic increases heart function in which there are activation of B1
AR (these are the only exception of stimulatory SNS receptors) that are
located in the SA node, AV node, atria, Bundle fibers and ventricle
With positive chronotropic activity (increased SA node activity)->
increased conduction-> positive dromotropic activity (AV node
activation)-> Can cause for abnormal automaticity foci to be stimulated
(positive bathmotropic activity)-> Increase risk of arrhythmias (by
overstimulation of Purkinje fiber)-> increased forceful ventricular
contractions (positive Inotropic activity)
With all this HR, SV and CO increase and because of that cerebral and
coronary blood flow increase

Blood flow to the GIT is less, sphincter gets activated to constrict with a1
AR activity, peristalsis is inhibited and not activated with B2 AR activity,
splanchnic blood flow is less, decreased resorption and absorption
In the bladder the detrusor muscle has to be inhibited as it is relaxed and
has B2 AR activation, sphincter should be stimulated and is activated via
their A1 AR.
The non-pregnant female uterus has a1 AR that contract under
sympathetic outflow, but a pregnant female starts to express more B2 AR
as she goes through the trimesters because its a natures way of
preventing contractions to cause harm to the baby

Pancreas has Islet

of Langerhans that
have b cells that
produce insulin
Hepatocytes takes
up glucose from the
blood and makes
glycogen via
glycogenesis
Glycogen then is
broken down into
glucose in a
reaction called
glycogenolysis
This releases glucose into
the circulation
With sympathetic outflow
there is an increased need
for energy fuels in the blood
So glucose levels rise, free
fatty acids rise
Epinephrine acts on the
modified B3 AR of adipocytes
-> this stimulates enzymes
that start breaking down TG
(lipolysis)
Glycerol and free fatty acids
will go into the blood stream
Free fatty acids go to the
liver and leads to the
formation of more glucose
(this is through a breakdown product of altererd carbon skeleton of fats
and not carbohydrates=>gluconeogenesis)
Pathway of glycogenesis is inhibited and glycogenlysis increases

In order to maintain high levels of glucose in the blood during stress

response, then there should be less release of insulin; this means there is
inhibition of B cells of pancreas via the a2 AR.
There is a release of K+ from the liver cells, because during increased
excitation of skeletal muscle there are a lot of Na going into the cells and
K+ ions going out (repolarization).
o The K+ goes through a cotransport with glucose
o The K+ that leaves the skeletal muscle cell is reabsorbed back into
the cell via Na+-K+ ATPases that bring back in K+
o Epinephrine increases the activity of ATPases so that K+ is quickly
reabsorped to induce the next depolarization and thus preventing
hyperkalemia which can occur because of the K+ releasing from the
liver and muscle cells
Skeletal muscles have extrafusal fibers and intrafusal fibers (spindle
fibers)
Muscle spindles maintain the tone of the muscles and they are the
sensory system of muscles and are stretchometers
When adrenaline levels go up there are tremors
When hand is steady this means that flexors and extensors regulate the
tone equally because the brain is receiving correct proprioceptive
information from the body and relaying the correct info
Epinephrine stimulates the muscle spindles to desynchronize and the info
to the brain is not accurate and the muscle becomes dysfunctional
Under stresses, anxiety, fear and thyrotoxicosis will lead to tremors
because of increased sympathetic overflow
o T3 and T4 enter the cells and induce genes of AR to increase the
formation of excess AR to the respective tissues=> normal levels of
epinephrine, but oversensitive target organs
B2 stimulant drugs all have a side effect of tremor; salmetorol, albuterol,
terbutaline, &*()_
These drugs are also used as bronchodilators, they act on B2 AR and
relax bronchiolar smooth muscle, but will act on muscle spindles and
cause tremors
Salmeterol may cause tremor, hyperkalemia, hyperglycemia

SNS vs. PNS

Epinephrinie stimulates B1 AR on the SA node cells of the heart:

o It activates the Gstimulatory protein subunits a (a, b, gamma)
o This activates the Adenylyl cyclase enzyme to convert ATP to cAMP

o Increased intracellular cAMP

levels trigger the activation
of Protein Kinase enzyme A
o This phosphorylates of
certain cationic channels
which will lead to
overfunctioning
o Thesse channels open up
more frequently and the
extracellular Na+ and Ca+
will come inside to the cell
and start loading into the
cell
o Cells resting membrane
potential will come closer to
threshold action potential
and thus making the cell
more excitable
o The actions on the SA node
cells mimic the effect of
epinephrine on all cardiac
cells and Ca+2-dependent mechanical activities will increase in the
heart => TACHYCARDIA

Acetylcholine stimulates the M2 cholinergic receptors on the SA node cells

o This stimulates the Ginhibitory protein and hti swill inhibit the
adenylyl cyclase activity
o There is reduced production of cAMP from ATP
o Protein Kinase A activation is decreased
o Phosphorlyation of channels decreases
o Cationic loading is decreased
o Total cations are less and the RMP moves away from the threshold
potential and the speed with which it reaches threshold is
decreased and the firings decrease =>BRADYCARDIA
The adrenergic system will work on the cells and it will act on the
cholinergic nerve ending to inhibit its action via a synapse
The synapse will release NE to activate the a2 AR on the cholinergic nerve
ending that is fused with Ginhibitory protein and this ultimately leads to
inhibition of nerve ending.
When there is too much vagal activity= There will also be a vagal nerve
ending synapse coming from the cholinergic nerve ending that will release
Ach to the M2 AR on the adrenergic nerve ending
Heart is more under PNS activity than SNS activity
As cAMP is being formed by sudden sympathetic activity (when you hear
good news) it is destroyed immediately into AMP by phosphodiesterases
Caffeine intake inhibits the function of phosphodiesterases and cAMP will
increase even though there is normal level of adrenaline and ultimately
being sympathetic overdrive to the tissues
Phosphatases work on the phosphates attached to the cationic channels
and dephosphorylate them
When Ach stimulates the M2 AR it triggers the subunits b and gamma to
go and activate K+channels and they will take the RMP away from the
thereshold potential

Parasympathetic Nervous system

As the polysynaptic parasympathetic fibers descend along the spinal cord

they stimulate PNS centers in the brainstem; the upper part of midbrain,
lower part of pons, and medulla to provide parasympathetic outflow
The nucleus located in the upper part of the midbrain is called EdingerWestphal nucleus

The nucleus located in the lower part of pons is called superior

salivatory/lacrimatory nucleus and inferior salivatory nucleus
The nucleus located in the medulla is dorsal nucleus of Vagus
The highest outflow is of PNS is at the upper level of midbrain along with
the 3rd cranial nerve (oculomotor) that are preganglionic
They will go to the ciliary ganglion and they will become postganglionic
parasympathetic fibers which will come out as short ciliary nerves
These short ciliary nerves come out and pierce the sclera and enters the
eyeball and traverse forward between the choroid and sclera
They will provide innervation to the ciliaris and terminally innervate the
sphincter pupillae
Parasympathetic fibers have usually long preganglionic fibers and short
postganglionic fibers, PNS usually have ganglia more away from the CNS
and usually located near to the target tissue
The PNS fibers of GIT, heart are present within the walls of the viscera
Ciliaris will contract because of the PNS inflow by the triggering Ach
release that activates the M2 receptors, the posterior part will move
forward and inward with lens becoming globular => eye accommodates
for the near vision
Pupillary Miosis: There are postganglionic fibers that go directly to the
pupillary sphincter with Ach release that activate M3 receptors
o It is coupled with Gq that activates Phospholipase C
o This breaks down Phosphatidyl Inositol diphosphate into DAG and
IP3
o IP3 act on SR pumps and release Ca+2 that will act on contractile
machinery of the cell
o Ca+2 binds with calmodulin kinases and this phosphorylates the
myosin light chains
o This leads to calcium loading cell contraction
There are preganglionic fibers that come from the superior
salivatory/lacrimatory nuclei along with 7th cranial nerve (facial)
These fibers reach the pterygopalatine ganglion; some of them go from
there and through the inferior orbital fissure and supply the lacrimal
glands and some of them will go through splenopalatine/ptyergopalatine
foramen to supply the nasal and palatine glands
There are more fibers that come from the superior sailivatory nucleus
that run along with CN VII they go through the middle ear and as a part
of the chorda tympani they run out and go to the submandibular ganglion
and from there some go sublingual and submandibular glands

From the inferior salivatory/lacrimatory nucleus there are preganglionic

fibers that exit along with the CN IX (Glossopharyneal) and they go to the
otic ganglion and the postganglionic fibers will go to through auricular
temporal nerve branch going to the parotid gland
There are fibers that come form the dorsal nucleus of Vagus as
preganglionic fibers that go on to supply many structures: pharynx,
larynx, esophagus, viscera in the neck, chest, abdomen, lungs, heart,
esophagus, stomach, duodenum, jejunum, ileum, cecum, ascending
colon, tranverse colon
Lower abdominal and pelvic viscera are supplied by the outflow form
sacral units (S2-S4) stimulated by the descending pathways
Sidenote: Parasympathetic outflow is craniosacral
Sacral nerves that eventually become pelvic nerves and they supply the
last part of descending colon, sigmoid colon, rectum, urinary bladder,
genitalia
Bundle fibers on the heart are made up of specialized myocardial cells
SA nodes have a great automaticity and
AV node has slow conducity and Purkinje
fibers have fast conductivity
Right vagus nerve supplies the SA node
and left vagus nerve supplies the AV node
Vagus nerve provides the secremotor
functions to the GIT as well through the
release of Ach
Glandular cells when they are loaded with
Ca+2 they release their secretions
When Ach is released increasingly to the
GIT there can be a risk of acquiring peptic
ulcer
The vagus nerve goes through the effector
organ and it goes through the intramural ganglion that are located in the
walls of the bronchi, GIT and from there, there are very small
postganglionic fibers

Innervation of Urinary Bladder

There is a special type of smooth musce surrounding the bladder called

the detrusor muscle
It consists of millions of muscle fibers and is interconnected with junctions
where electrical impulses jump from one to another
When it contracts it contracts together
There is an internal urethral
sphincter that has a pelvic
muscle beneath it called the
levator pelvic floor muscles
There is a membranous part
of the urethra that passes
through this area and there is
a special type of internal
urethral sphincter that works
automatically and external
urethral sphincter is working
under voluntary control
On average there is 1ml of
urine per minute being
produced and the bladder is
holding in it until it reaches 60
ml level
As the amount of urine
increases the tension and
pressure does not change
because the bladder
accommodates with increase
in size
During stage Ia it follows the
LaPlaces law P=2T/radius
What allows the bladder wall
to stretch? It is the property
of the bladder muscle having plasticity and the neurological mechanism
that increases the radius of the bladder is sympathetic activity
There are sensory systems that are located in the trigone and body of the
bladder and they are taken up the dorsal root of the spinal nerve
Sensory output by the bladder is becoming input to the CNS at the sacral
area and the info ascends to the pontine centers that is related to the
function of micturition and the midbrain centers are inhibitory
The info goes to the cerebral cortex medially and these sensations
produce the conscious awareness that the bladder is being filled
There is sympathetic outflow from the lateral horns that stimulate the
sympathetic fibers that go through the hypogastric ganglion and to the
detrusor with NE and epinephrine and activated via the B2 AR that are
inhibitory =>detrusor muscle will relax

Some of the sympathetic fibers will go to the internal sphincter with

release of NE that act on the a1 receptors=> internal sphincter
constriction
From the lateral horns there are parasympathetic fibers that go to the
detrusor and internal sphincter and the ganglion are intramural
Sympathetic outflow is form the lumbar and parasympathetic is from
sacral
When sensations enter the sacral section it activates parasympathetic
outflow and there is a decision in mature adults whether there is to be
urine outflow or not from higher centers; if not parasympathetic would be
inhibited
There is somatic outflow from the pudendal nerves and they will stimulate
the external urinary urethral sphincter it comes from the nucleus of Onuf
from the sacral segments
The higher centers have maximum outflow of sympathetic and minimum
level of parasympathetic and maxiumum outflow of enteric nervous
system when controlling urine
Descending information reaches the pontine micturition centers that will
facilitate the lower centers to pass urineand inhibit the outflow
Inferior orbital cortex decides whether its the right environment to
urinate and the final decision is made by the paracentral lobules and
there are cortical descending pathways that influence the centers of the
brainstem
These stimulate the pontine centers and these will facilitate the
descending info to urinate and as they come down stimulate the
parassympathetic outflow and inhibits the sympathetic outflow and
inhibits neurons that activate the external urethral sphincter
This relaxes the muscles of pelvic floor and external urethral spincter
Decreases sympathetic outflow from L1-L3
Little urine trickles into urethra and that has very sensitive sensory nerve
endings that leads to very heavy firing to the sensory system along the
sympathetic and pudendal nerves and this will induce the local sacral
spinal reflex for parasympathetic outflow facilitated by higher centers
The fibers will then release Ach to the detrusor to contract and to the
internal urethral sphincter to relax
Urine will push through the urethra and urination assumes
Parasympathetic outflow is being regulated by higher centers, local sacral
spinal reflex,
Tabes Dorsalis is a disease where there is dorsal root ganglion have
fibrotic and inflammatory changes this does not allow for the bilateral flow
of sensory information to higher centers
o In this patient as urine amount increases in the bladder leading to it
to be increasingly distended, there will be no reciprocal motor
information from the brain to release the urine because of dorsal
root damage (no sensory input)

o The sacral spinal reflex does not work and this leads to the bladder
getting larger, overfilled, and thin walled and with time there will be
overflow incontinence =>DEEFFERNTATION
Bilateral denervation of the bladder is due to lesions of the caudal equina
o All the sensory and motor connections from the sacrum to and from
the bladder are lost
o It leads to an automatic/decentralized/denervated small bladder
o The myogenic reflex of the bladder it will release partial urine as
soon as it is filled
o Because of the partial excretion of urine and the building of
pressures within the bladder it results in a hypertrophied bladder
o When you cut the nerves to the bladder there will be more
expression of receptors on the bladder
Lower lumbar and sacral connections are disconnected from the higher
centers
o There is no ascending information to the higher centers of the brain
of the filling bladder
o Initally if the polysynaptic pathway of neurons are cut off from the
creating a flaccid bladder and it goes through a shock phase with no
firing of the neurons, then overfiring of the bladder leading to an
automatic bladder

Clinical Correlates of ANS

Hirschsprungs Disease (Megacolon)

o The GIT is innervated by the autonomic nervous system via the
autonomic ganglion that is derived from neural crest cells

o This disorder results because

there is an impaired
migration of crest cells
leading to later part of the
large intestine being
aganglionic due to a mutation
of a RET gene
o Supply of the GIT from
esophagus end of
tranverse colon is by the
vagus nerve: This area works
fine with peristalsis with the
GIT propelling the food
forward
o Supply of the GIT from the
descending colon rectum is
by the pelvic nerves:
peristalsis cannot move
forward through these
segments so food contents
stay trapped and the intestine
distends proximally to the
aganglionic sections which
are underfilled and shrink (usually found at the site of the rectum)
Familial Dysautonomia
o Autosomal recessive disorder
o There is progressive neuronal loss or degeneration in autonomic
sensory ganglion
o Clinical presentations of abnormal sweating patterns, random
fluctuations in blood pressures, hypotonia (babies not being able to
feed well)
Raynauds Disease
o Vasculature of the distal part of the limbs is oversensitive to the
cold/sympathetic overflow/emotions (hyperconstriction)
o With excessive constriction the hand will become pale and the blood
flow will stop and the vessels become spastic (blood slows down)
o Usually 25% of the O2 is deloaded from arterial blood hemopglobin
to the tissues when it is travelling up the venous system again, but
in this disease there is increased extraction (<5ml) of oxygen from
hemoglobin because of blood stagnation cyanotic limbs
o If the blood moves really slowly hypoxia of tissues anaerobic
glycolysis (lactic acidosis increased production of vasodilators
reactive vasodilation (tissue is hyperemic and red colored)
o Raynauds phenomenon is like Raynauds disease in that they have
extreme vasoconstriction in cases of extreme cold, but is associated
with some underlying condition
Peptic Ulcer

o Hyperactivity of the vagus nerve/ response of parietal cells to vagal

stimulation is excessive
o This results in increased production of HCl which damages the GIT
mucosa peptic ulcer
Botulism
o Caused by the bacteria Clostridium botulinum that multiplies in
anaerobic environments with tightly packed foods
o Produces an exotoxin botulinum toxin which causes:
- Impairment of NMJ
- Flaccidity
- Effects cholinergic nerve endings so they cant release Ach
- Normally, with a Na+ charge to the neuron, it stimulates a
Ca+ influx leading to the binding of carrier protein
synaptobrevin attached to the vesicle with Ach to
synaptotagmin fusion of the vesicle with plasma membrane
releases Ach into the synapse
- The botulinum toxin degrades (proteolysis) the synaptobrevin
protein and prevents the release of Ach failure of cholinergic
transmission/NMJ
- Black widow spider toxin (latrotoxin) helps the
hyperfusion of synaptobrevin and synaptotagmin leading to
increased fusion of vesicle and cholinergic nerve ending
membrane leading to a cholinergic crisis; excessive sweating,
salivation, lacrimation, defecation, micturition
- Clostidium tetani can infect via the blood stream and the
nervous system and reaches the spinal cord
- LMNs (alpha motor neurons) have a tendency to overfire and
they are inhibited by inhibitory interneurons (Renshaw cells)
- Renshaw cells contain lots of glycine (inhibitory
neurotransmitter) that gets released
- When tetanus toxin accumulates in Renshaw cells it breaks
down synaptobrevin which leads to the failure of glycinergic
nerve endings overfiring of LMNS with spasticity
Shy-Drugger syndrome

o Preganglionic sympathetic neuronal loss SNS does not work:

problems with sweating, impotency (ejaculatory problems),
fluctuates of BP, urinary bladder atonicity

ANS and Drugs

Sympathomimetic Drugs
Group of drugs when administered to a person they mimic the actions of
sympathetic nervous system activation
These drugs act on receptors 1 Adrenergic receptors, 1 Adrenergic
receptors and 2 Adrenergic receptors
It is important to know the differences between the catecholamines
There are two classes of of sympathomimetics: direct and indirect

Direct Sympathomimetics
(Catecholamines)
Examples: Epinephrine,
Norepinephrine, Dopamine

Indirect Sympathomimetics (NonCatecholamines)

Examples: Amphetamine,
Ephedrine (mixed), Cocaine,
Tyramine
MOA: These drugs act directly on MOA: These agents may block
or receptors, producing
the uptake of norepinephrine
effects similar to those that
(uptake blockers) or are taken
occur following stimulation of
up into the presynaptic neuron
sympathetic nerves or release of
and cause the release of
the hormone epinephrine from
norepinephrine from the
the adrenal medulla
cytoplasmic pools or vesicles of
the adrenergic neuron. As with
neuronal stimulation, the
norepinephrine then traverses
the synapse and binds to the
or receptors.
Cannot pass through biological
Can pass through biological
membranes (eg. Blood brain
membranes (blood-brain barrier)
barrier)
Given paraenterally (injection,
Given orally
implantation and infusion)
Short duration of action
Long duration of action (hours)
(minutes)
More polar
Less Polar
More potent
Less Potent
Structure: Has 3,4 hydroxylated Structure: Has no hydroxylations
phenyl ring (3,4on phenyl ring
Dihydroxyphenyl(catechol)
ethylamine)

There is an enzyme that will remove the hydroxyls from the phenyl ring
of catecholamines and add methyl groups in its place
CATECHOLMETHYLTRANSFERASES more lipid soluble molecule
o These do not metabolize indirect sympathomimetics

Drugs and their actions on AR

The part of the catecholamine that determines whether it binds to
1/1/2 receptors is the amino end of the molecule; Affinity for
receptors increases, as group on the amine nitrogen gets larger.
o Norepinephrine has just an amino group at the end
o Epinephrine has a methylated amino group at the end
o Isoproterenol has an isopropylated amino group at the end
o Salmetereol has a very bulky amino group at the end
These drugs bind to their corresponding adrenergic receptors by size
Epinephrine binds with all the AR, but with low doses
binds with 2 AR then eventually all of
them: 2>1>1

(arterioloconstriction+cardiostimulation+bronchodilation+hyperglycemia+
hyperkalemia+tremors)

Norepinephrine has a lighter amino group and will bind with 1>2>1
and binds very little to B2 AR (arterioloconstriction + cardiostimulation)

Isoproterenol has a heavier amino group than the prior groups and will
bind to 1=2 equally and little/no a1 AR activity
(cardiostimulation+bronchodliation+hyperglycemia+hyperkalemia+tremo
rs)
Salmeterol has a very heavy amino group and would only primarily bind
to 2 AR>1 (bronchodilation+hyperglycemia+hyperkalemia+
tremors+little cardiostimulation)
o If you wanted to treat a patient with asthma it would be ideal to
treat the patient with salmeterol as 2 AR effect would cause the
bronchodilation dominantly
o It still is better to take it via inhalation so it reaches the site of
action, instead of it acting systematically in which there would be
B2 action of glycogenolysis and tremors.
Dopamine (with no b hydroxylation) binds with dopaminergic AR and to
lesser degree 1>1
o Dopaminergic AR are found on splanchnic and renal circulation
o When these renal dopamine receptors are stimulated renodilation
o This is drug is ideal for patient with need for cardiac stimulation and
who is under shock and has decreased renal perfusion (acute
tubular necrosis)
o During shock there is severe sympathetic overflow and severe
constriction of blood vessels ischemia to the kidney acute
tubular necrosis
o Slow infusion of dopamine will stimulate the heart to maintain the
blood pressure (+inotropic action) and it will dilate the renal vessels
risk of ATN
o Increased infusion of dopamine will cause 1 actions and renal
protective mechanism is lost and vasoconstriction resumes
Dobutamine is a drug in which there is increased 1 action>2>1 and
ideal for patients with problems in heart rate regulation with normal
kidneys

Non-catecholamines can be metabolized

by Monoamine oxidases that lie on the
-carbon on the molecule and remove
the hydroxyl on the -carbon
But this enzyme can be counteracted by
adding a methyl to the -carbon and
amino group so it has not site of action
making the drug resistant to damage
and duration of drug.

Drugs and their Effects on Cardiac Profiles

When NE is injected there is an increase in the total peripheral resistance

(arterioloconstriction) diastolic afterload pressure slight in systolic
BP in heart rate
o But it leads to in pulse pressure

When there is an administration of epinephrine, the effect is more

dependent on the dosages of the drug
o Low
dose:

(primarily 2 action) TPR (vasodilation) Diastolic BP Heart

rate (reflex tachycardia+1 stimulation) systolic BP (because of
increased cardiac output)
The pulse pressure increases because of the decrease in
diastolic BP and the severe increase in systolic BP
o Intermediate dose: primarily 2+1 action leads to no change in
TPR and diastolic pressure
o High dose: primarily 1 action leading to increases in TPR and
diastolic BP
When there is an administration of Isoproterenol there is equal 1 and 2
action there is TPR Diastolic BP Heart rate (severe reflex
tachycardia (because of vasodilation) + 1 cardiostimulation)
systolic BP pulse pressure