Transcript ans-pharmacology-for

The Autonomic Nervous System
Def: The ANS consists of all visceral motor
neurons innervating smooth muscle, cardiac
muscle and glands.
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Divide Autonomic Pharmacology into
Four Categories:
1. Drugs that increase the sympathetic
nervous system response
2. Drugs that increase the
parasympathetic response
3. Drugs that block the sympathetic
nervous system response
4. Drugs that block the
parasympathetic response
Sympathetic Nervous System
- Adrenaline Rush
- Autonomic nervous system response to
fear, anger, stress
Parasympathetic Nervous System
- Rest and Digest
- Relax, Repair, Renew
Sympathetic Parasympathetic
Agonist
Antagonist
Sympathetic Parasympathetic
Agonist
Antagonist
Sympathetic Parasympathetic
Agonist
Antagonist
-
Autonomic Nervous System
Autonomic means automatic
You do not control your ANS, it works
automatically
Controls the functions of MANY organs
automatically
That’s why many drugs that affect the
ANS affect many organs
Drugs that affect the ANS will affect many
organs:
Heart
Lung airways
Blood vessels
Bowels
Pancreas
Ureters
Bladder
Eyes
Pupils
Lacrimal gland
Salivary glands
Do not confuse the autonomic nervous
system with:
Peripheral Nervous System
- Outside of skull and spinal cord
- Neurons end on organs and muscle
- Central Nervous System
- Brain and spinal cord
- Neurons end on other neurons
Do not confuse the ANS with Voluntary
Nervous System
- Voluntary means willing, like to volunteer
- You do control your voluntary nervous
system
- You control your skeletal muscles to
move your body
The autonomic nervous system is divided
into two systems:
A. Sympathetic
- Adrenaline rush
- Fear, flight, fight
B. Parasympathetic
- rest, repair, digest
Can you guess what is happening
to this girl’s organ function?
Running is voluntary in this case (she has
no choice) 
But everything else is automatic
- Effects of epinephrine or adrenalin
- (heart is pounding)
Adrenergic Receptors
- Heart is innervated by sympathetic
neurons
- Norepinephrine
- The heart senses Adrenaline from
Adrenal
- Epinephrine is adrenalin
- Adrenergic Beta 1 receptors
Effects of Epinephrine – Adrenaline
Lung Airways WIDE OPEN
BP is high – systemic vessels constrict
Adrenergic Receptors
- Blood vessel smooth muscle is
innervated by sympathetic neuron
- Norepinephrine
- Receptors also sense adrenaline from
adrenal
- Epinephrine
- Adrenergic Alpha 1 receptors
Adrenergic Receptors
- Lung bronchiole smooth muscle is
innervated by sympathetic neuron
- Norepinephrine
- Blood vessels sense adrenaline from
adrenal
- Epinephrine
- Adrenergic Beta 2 Receptors
Effects of Epinephrine – Adrenalin
- Blood to muscles increased
- Blood to GI decreased
- Pupils dilated
Norepinephrine – neurotransmitter that
dilates lungs, constricts blood vessels, lung
airways open, shutting down GI tract
Why are all these changes occuring?
- Sympathetic nervous system
(Norepinephrine)
- Adrenal gland – on top of kidneys (that
extra boost)
- Adrenalin (Epinephrine)
- Adrenergic Neurons or Adrenergic
Agonist
- Adrenergic System
Adrenergic Agonists
- Adrenergic Agonist substances are also
called sympathomimetics
Epinephrine or Adrenaline
- Adrenaline is an adrenergic agonist
- increased heart rate
- constricts blood vessels
- dilates lung airways
- dilates pupils
Albuterol
- Is an adrenergic beta agonist used in
asthma, what are some of its other
effects besides bronchodilation?
- Increased heart rate
- Increased blood pressure
Adrenergic Antagonists
- Beta blockers are common drugs used to
treat high blood pressure
- Beta blockers are common drugs used to
treat high eye pressures (glaucoma)
Asthma
- Do you understand why beta blockers
can make asthma worse?
- That’s why one of the reasons we try to
use cardioselective beta blockers in
patients with asthma
Autonomic Nervous System
- Although we have discussed many organ
functions
- We have only discussed HALF of the
Autonomic Nervous System
- The other half does the opposite
Can you guess what is happening to his
heart rate? His blood pressure?
Effects of parasympathethic tone
This is the rest and digest system
- Acetylcholine – neurotransmitter
- Muscurinic receptors
Parasympathetic Nervous System
Cholinergic
Agonism
Cholinomimetic
Rx: Bethanecol
- cholinergic muscurinic agonist
- used to stimulate bowel and bladder
function
Indirect Cholinergic Agonism
- Acetylcholinesterase inhibitors
- Blocking the breakdown of acetylcholine
increases acetylcholine levels
- Acetylcholineterase inhibitors are
cholinomimetic
- Rx: Neostygmine
- Toxin: Organophosphate –
acetylcholinesterase inhibitors
Cholinergic Antagonism
Rx: Atropine – classic cholinergic antagonist
- Cholinergic muscuranic antagonist
- Anticholinergic
- Antimuscuranic
Rx: Atropine
- Speeds up heart rate
- Emergency treatment for bradycardia
(slow heart rate)
- Atropine also causes mydriasis
- Atropine used for diarrhea
- Atropine used as antidote for
organophosphate poisoning
Asthma
- Beta agonists are used in asthma
- But so are cholinergic muscuranic
blockers
DuoNeb for Asthma contain two drugs
- Rx: Albuterol – beta2 agonist
- sympathomimetic
- Rx: Ipratropium – anticholinergic
- antimuscarinic
- parasympatholytic
-
Heart rate up or down
Blood pressure up or down
Eye pressure up or down
Lung airways open or closed
Bladder relax or less relaxed
GI stimulate or slow
Dilating the pupils is – Mydriasis
Dilating the pupils is – Mydriasis
Both
Sympathomimetic adrenergic drugs
and
Anticholinergic parasympatholytic drugs
cause mydriasis
Constricting the pupils is Miosis
- Both sympatholytic adrenergic antagonist
drugs
and
- Cholinergic parasympathomimetic drugs
cause miosis
Dry lacrimal glands
- Both sympathomimetic adrenergic drugs
And
Anticholinergic parasympatholytic drugs
Cause dry eyes
Stimulate lacrimal glands to make tears
- Both sympatholytic adrenergic antagonist
drugs
and
Cholinergic parasympathomimetic drugs
Stimulate tear production
Dries salivary glands
Both sympathomimetic adrenergic drugs
And
Anticholinergic parasympatholytic drugs
Cause dry mouth
Stimulates salivary glands to make saliva
- Both sympatholytic adrenergic antagonist
drugs
and
Cholinergic parasympathomimetic drugs
Stimulate saliva production
Both sympathomimetic adrenergic drugs
And
Anticholinergic parasympatholytic drugs
Dry respiratory airways
Both sympatholytic adrenergic antagonist
drugs
And cholinergic parasympathomimetic
drugs
Can stimulate airway secretion
Bronchodilation: relaxing bronchiole smooth
muscle to open airways
Both sympathomimetic adrenergic drugs
and
Anticholinergic parasympatholytic drugs
Cause bronchodilation and are used in
asthma
Bronchoconstriction/Bronchospasm:
contracting bronchiole smooth muscle to
close or constrict airways
Both sympatholytic adrenergic antagonist
drugs
And
Cholinergic parasympathomimetic drugs
Can cause bronchospasm
Drugs that cause tachycardia (fast heart
rate) are called positive chronotropes
Both sympathomimetic adrenergic drugs
And
Anticholinergic parasympatholytic drugs
Cause tachycardia
Drugs that increase the force of contraction
are positive inotropes
Sympathomimetic adrenergic drugs are
positive inotropes
Drugs that cause bradycardia (slow heart
rate) are called negative chronotropes
Both sympatholytic adrenergic antagonist
drugs
And
Cholinergic parasympathomimetic drugs
can cause bradycardia
Drugs that decrease the force of contraction
are negative inotropes
Sympatholytic adrenergic antagonist drugs
are negative inotropes
Vasoconstriction: contracting arteriole
smooth muscle to raise blood pressure
Sympathomimetic adrenergic drugs raise
blood pressure by vasoconstriction
Vasodilation: relaxing arteriole smooth
muscle to drop blood pressure
Sympatholytic adrenergic antagonist drugs
can drop blood pressure
Some drugs relax the GI tract and slow
peristalsis
Both sympathomimetic adrenergic drugs
And
Anticholinergic parasympatholytic drugs
Slow peristalsis, relax GI
Some drugs stimulate peristalsis in the GI
tract
Cholinergic parasympathomimetic drugs are
used to stimulate GI
Drugs that affect autonomic nervous system
may affect the pancreas
Some drugs relax the bladder and urinary
tract smooth muscle and slow peristalsis
Both sympathomimetic adrenergic drugs
and anticholinergic parasympatholytic drugs
slow ureter peristalsis and relax bladder
Some drugs stimulate the smooth muscle of
the bladder and urinary tract, increasing
peristalsis
Cholinergic parasympathomimetic drugs are
used to stimulate the bladder
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Sympathetic and Parasympathetic Divisions
of the ANS
• How they are similar:
– Both divisions are part of the
ANS
– Both have effects on smooth
muscle, cardiac muscle and
glands
• How they differ:
– Stimulation of effectors by
each system vary from one
body system to another.
Effects may be stimulatory or
inhibitory.
– Location
– Length of pre and
postganglionic fiber
– Neurotransmitters used
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Comparison of ANS and Somatic Motor
Pathways
• Somatics
– Single neuron from spinal
cord to effector
– One neuron innervates the
effector cell
– NTS is acetylcholine (ACh)
• Autonomics
– Two neurons relay (ganglion)
to effector
– Dual innervation of effectors
– NTS at ganglia (ACh); NTS at
effector can be ACh or
norepinephrine
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Location and neurotransmitters used
by Sympathetic/Parasymp
adrenergic receptors
sympathetic
preganglionic neuron
postganglionic neuron
parasympathetic
nicotinic receptors
muscarinic receptors
Characteristics of Sympathetic and
Parasympathetic Function
•
Post-ganglionic sympathetic nerves release
norepinephrine at their nerve endings
– these nerves are called adrenergic nerves
•
Pre and post-ganglionic parasympathetic nerves
release acetylcholine at their nerve endings (Nitric
oxide- corpora cavernosa)
– these nerves are called cholinergic nerves
•
EXCEPTION FOR SYMPATHETIC:
– Cholinergic: mACH; used in body wall.
– Vasodilation of vessels in brain and skeletal
muscle
– Piloerector muscles
– Sweat glands
– Nitric oxide: vasodilation of vessels in brain,
skeletal muscle
Sympathetic
Nervous System
“Thoracolumbar”
When active?
Length of pre and
postganglionic
nerve?
Location of cell
bodies of
preganglionic nerve?
Location of cell
bodies of
postganglionic
nerve?
Neurotransmitters
released?
Adrenal medulla
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
Figure 60-1;
Guyton & Hall
Receptor Where found?
Actions
 1a
Iris, intestine, heart and
arteries
Increased inotropy, closure of GI
sphincters, vasoconstriction, pupil
dilation
 1B
Arteries, heart
Increased BP, vasoconstriction
 2a
Vascular endothelium
and adipocytes
Lipid metabolism
 2b
Vascular endothelium
Increase vasoconstriction
(increased MI mortality
w/polymorphism)
 2c
Vascular endothelium
Presynaptic control/ release of NT
1
HEART, kidney,
adipocytes
Increased heart rate and inotropy
2
Respiratory tract, GI,
glands, hepatocytes
Inhibitory, relaxation of resp. tract to
get dilation
3
Adipose tissue
Lipolysis and thermogenesis
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Parasympathetic
Nervous System
“cranio-sacral”
Parasympathetic nerves originate
from cranial nerves III, VII, IX, and X
and the sacral spinal cord.
occulomotor nerve - fibers to
the pupillary sphincters and
ciliary muscle
facial nerve - fibers to lacrimal
and submandibular gland
glossopharyngeal nerve - fibers
to parotid gland
vagus nerve - motor inputs to
visceral organs
sacral segments - fibers to
descending colon, rectum,
bladder and genitalia
Figure 60-3;
Guyton & Hall
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Effects of the ANS on the Organs
• eye
– sympathetic --pupillary dilation
(alpha 1 receptor)
– parasympathetic--pupillary
constriction and
accommodation (focusing) of
the lens (mACh receptor)
• glands of the body
– parasympathetic stimulate the
nasal, lacrimal, salivary, and
G.I. glands (mACh receptor)
– sympathetic stimulates the
sweat glands (mACh receptor)
Effect of the Autonomic Nervous
System on the Organs
• G.I. tract
– parasympathetic stimulates overall
activity including G.I. smooth muscle
– sympathetic has very little effect
• heart
– sympathetic increases the rate and
contractility
– parasympathetic decreases heart rate
• blood vessels
– sympathetic causes vasoconstriction.
Reduced sympathetic response accounts
for most vasodilation.
– parasympathetic causes some
vasodilation (e.g., penis)
Sympathetic and Parasympathetic
“Tone”
• the basal rate of activity of
each system
• this background activity
allows for an increase or
decrease in activity by a
single system
– sympathetic tone
normally causes about a
50 % vasoconstriction
• increasing or decreasing
“tone” can change vessel
diameter
– parasympathetic tone
provides background
G.I. activity
adrenergic or sympathomimetic drugs act
like norepinephrine
• these drugs have an effect which is much more prolonged than
that of either norepinephrine
– phenylephrine stimulates alpha receptors
– isoproterenol stimulates both beta1 and beta2 receptors
– albuterol stimulates only beta2 receptors
• some drugs act indirectly by increasing the release of norepi
from its storage terminals
– ephedrine, amphetamine, pseudoephedrine,
Pharmacology of the Sympathetic
Nervous System
• drugs that block the
effect of
norepinephrine
• alpha blockers
– phentolamine
– Cheap Viagra!
• beta blockers
– beta1 and 2 propranolol
Pharmacology of the Parasympathetic
Nervous System
• parasympathomimetic drugs
– muscarine
– pilocarpine
• activates muscarinic
receptors, cause profuse
sweating (why if sweat
glands are controlled by
sympathetic system?)
• cholinesterase inhibitors
– neostigmine, potentiates the
effect of acetylcholine
• antimuscarinic drugs
– atropine blocks the effect of
acetylcholine on effector cells