THE

AUTONOMI
C NERVOUS
SYSTEM
CC KANA LOU CASSANDRA BESANA
OVERVIEW
ANATOMY
FUNCTION
→ NEUROTRANSMITTERS

→ RECEPTORS

PHARMACOLOGY
 NERVOUS SYSTEM

CENTRAL NS PERIPHERAL NS

Brain Spinal Cord Sensory Motor

Autonomic Somatic

Parasympatheti
Sympathetic Enteric
c
ANATOMY
AUTONOMIC NERVOUS SYSTEM
AUTONOMIC
NERVOUS
SYSTEM
A network of nerves and ganglia that
provide involuntary control of the
physiological actions that maintain
internal homeostasis and respond to
stress.

Innervates structures within the

different organ systems, and central
nervous systems (CNS) and can
influence metabolism and thermal
regulation.
AUTONOMIC
NERVOUS
SYSTEM
3 major subdivisions:
SYMPATHETIC, PARASYMPATHETIC
and ENTERIC NS
SYMPATHETIC NERVOUS SYSTEM
Sympathetic nerve fibers originate in the spinal cord

Each sympathetic pathways from the cord to the stimulated tissue

is composed of two neurons: preganglionic neuron, and a
postganglionic neuron

Preganglionic fibers of the SNS originate from the thoracolumbar

region of the spinal cord (T1-L2/3)

Cell bodies lie in the spinal gray matter

 1

3
SYMPATHETIC NERVOUS SYSTEM
Postganglionic neurons: either in one of the sympathetic chain
ganglia or in one of the peripheral sympathetic ganglia -> target
organs

Sympathetic nerve fibers in the skeletal nerves  blood vessels,

sweat glands, and piloerector muscles
SYMPATHETIC NERVOUS SYSTEM
Postganglionic neurons: either in one of the sympathetic chain
ganglia or in one of the peripheral sympathetic ganglia  target
organs

Sympathetic nerve fibers in the skeletal nerves  blood vessels,

sweat glands, and piloerector muscles

Segmentally distributed
SYMPATHETIC NERVOUS SYSTEM
Postganglionic neurons: either in one of the sympathetic chain
ganglia or in one of the peripheral sympathetic ganglia  target
organs

Sympathetic nerve fibers in the skeletal nerves  blood vessels,

sweat glands, and piloerector muscles

Segmentally distributed  Determined partly by locus in the

embryo
 PARASYMPATHETIC
NERVOUS SYSTEM
• Parasympathetic fibers leave the CNS through the cranial
nerves III, VII, IX, and X, as well as sacral segments S1-
S4
• ~75% of all parasympathetic nerve fibers are in the vagus
nerves (CN X)  thorax and abdomen
• Preganglionic fibers pass uninterrupted all the way to the
target organ; postganglionic neurons are located in the
wall of the organ.
 ENTERIC NERVOUS
SYSTEM
• Extensive, web-like structure that is capable of
functioning independently of the remainder of
the nervous system
• Regulation of digestive processes
• Two ganglionated plexuses: the myenteric
(Auerbach) and the submucosal (Meissner).
MYENTERIC SUBMUCOSAL
(AUERBACH) PLEXUS (MEISSNER) PLEXUS
Between the longitudinal Within the submucosa
and circular smooth
muscle of the GI tract

Coordinates with the Movement of water and

contractility of the electrolytes across the
muscle cells of the gut to intestinal wall
produce peristalsis
FUNCTION
AUTONOMIC NERVOUS SYSTEM
 FUNCTION
ACETYLCHOLINE NOREPINEPHRI
NOREPINEPHRIN
Cholinergic Adrenergic
All preganglionic neurons in both NE
E
Most of the postganglionic
sympathetic and parasympathetic sympathetic neurons (except to
Almost all of the postganglionic sweat glands and a few blood
neurons of the parasympathetic vessels)
system

PARASYMPATHETI SYMPATHETIC
 RECEPTORS ON EFFECTOR ORGANS
Binding of the
transmitter
substance with the
receptor

Conformational
change in the protein
molecule

Outside of the cell membrane, Change in Activating or

cell inactivating
bound as a prosthetic group to a
membrane an enzyme
protein molecule permeability
 CHOLINERGIC RECEPTORS
NICOTINIC RECEPTORS MUSCARINIC RECEPTORS
• Ligand gated ion channels • G proteins as signaling mechanism
• Found in autonomic ganglia at the • Found on all eff ector cells
synapses between the preganglionic stimulated by postganglionic
and postganglionic neurons of both cholinergic neurons of either
sympathetic and parasympathetic parasympathetic or sympathetic
systems nervous system
 ADRENERGIC
RECEPTORS
ALPHA RECEPTORS BETA RECEPTORS
• Alpha1 and Alpha 2 • Beta1, Beta2, and Beta3
• Linked to different G proteins • Also use G proteins for signaling
ADRENERGIC
RECEPTORS
BETA RECEPTORS
• Beta1, Beta2, and Beta3
• Also use G proteins for signaling
Autonomic
Effects on
Various
Organs of the
Body
Effect of Sympathetic StimulationEffect of Parasympathetic Stimulation
PHARMACOLOGY
AUTONOMIC NERVOUS SYSTEM
Cholinergic
Pharmacology
MUSCARINIC CHOLINESTERASE
ANTAGONISTS INHIBITORS
• Compete with neurally released • Impair the inactivation of
ACh for access to muscarinic ACh by the cholinesterase
cholinoreceptors; block ACh enzyme; sustain cholinergic
eff ects agonism
• Effects: Faster heart rate, • Reverse neuromuscular
sedation, dry mouth blockade and treat MG
• Bradycardia – most
prominent SE
 MUSCARINIC
ANTAGONISTS

• aka ANTICHOLINERGICS
• Esters of an aromatic acid combined with an organic
base
• Ester linkage – essential for eff ective binding to
ACh receptors
• MOA: competitively blocks acetylcholine
• Receptor subgroups:
• CNS – M1, M4, M5
• Autonomic ganglia and gastric parietal cells - M1
• Cardiac – M2
• Smooth muscle – M3
 • SA node - Tachycardia
• Shortens P-R interval,
decreases heart block
• Atrial arrhythmias, nodal
rhythms

GENERAL
• Atropine flush

• Inhibit respiratory secretions

PHARMACOLOGI • Relaxation of bronchial smooth

muscle
• Pronounced in patients with

C COPD or asthma

CHARACTERISTI • Stimulation - excitation,

restlessness, hallucinations
CS • Depression – sedation and
amnesia

Muscarinic Antagonists
 • Reduced salivary secretions
• Decreased gastric secretions
• Decreased intestinal motility &
peristalsis
• Reduced lower esophageal
sphincter pressure

GENERAL • Mydriasis
• Cycloplegia
PHARMACOLOGI
C • Decrease ureter and bladder
tone -> urinary retention

CHARACTERISTI
CS
• Inhibition of sweat glands ->
rise in body temperature
(atropine fever)

Muscarinic Antagonists
Muscarinic Antagonists
 ATROPINE SCOPOLAMINE GLYCOPYRROLATE
Mechanism of competes with prevents communication highest affinity for M1
Action acetylcholine for between the nerves of the receptors, followed by
cholinergic receptor sites vestibule and the vomiting M3, M2/M4, and M5
on the SA and AV nodes center in the brain
Indication Most efficacious Prevents motion sickness Potent inhibition of
anticholinergic for salivary gland and
treating respiratory
bradyarrhythmias secretions
Dosage 0.01 to 0.02 mg/kg Transdermal 1mg patch – Usual dose is half of
(usual adult dose of 0.4 to prevent PONV atropine
0.6 mg) 0.005 to 0.01 mg/kg to
0.2 – 0.3 mg in adults
Side effects Minimal CNS effects More potent Increases HR (IV)
Potent effects on the antisialagogue; greater Lower esophageal
heart and bronchial CNS effects sphincter relaxation
smooth muscles Clinical dosage usually result Antisialagogue effect
Antisialagogue effects – in drowsiness and
IM 0.01-0.02 mg/kg amnesia
Mydriasis and cycloplegia
Contraindicat CAD, narrow-angle closed-angle glaucoma Glaucoma,
Muscarinic
ions
Antagonists
glaucoma, prostatic obstructive
Cholinergic
Pharmacology
MUSCARINIC CHOLINESTERASE
ANTAGONISTS INHIBITORS
• Compete with neurally released • Impair the inactivation of
ACh for access to muscarinic ACh by the cholinesterase
cholinoceptors; block ACh enzyme; sustain cholinergic
eff ects agonism
• Effects: Faster heart rate, • Reverse neuromuscular
sedation, dry mouth blockade and treat MG
• Bradycardia – most
prominent SE
 CHOLINESTERASE
INHIBITORS

• Primary clinical use: reverse

nondepolarizing
neuromuscular blockers
• Inactivate
acetylcholinesterase by
reversibly binding to the
enzyme
• Indirectly increases the
amount of ACh to compete
with nondepolarizing agent ->
reestablishing neuromuscular
transmission
GENERAL
PHARMACOLOGIC
CHARACTERISTICS

Cholinesterase Inhibitors
 NEOSTIGMINE PYRIDOSTIGMIN PHYSOSTIGMINE EDROPHONIU
E M
Mechanism of Accelerate the Inhibits Reversible Reversible
Action reversal of acetylcholinesteras cholinesterase inhibitor inhibitor of
neuromuscular e in the synaptic that helps prolong the cholinesterase
blockade  build up of cleft activity of acetylcholine
acetylcholine Not cross the BBB
Not cross the BBB
Indication used to treat MG, prevent Treat glaucoma preventing post-
urinary bladder atony, bradycardia Treat CNS effects of op shivering; tx
and paralytic ileus Treat myasthenia atropine overdose and of overdoses of
gravis other anticholinergic atropine
drug
Dosage 0.08 mg/kg (up to up to 0.25 mg/kg 0.5 to 1 mg/kg 0.01 – 0.03
5mg in adults) (20 mg in adults) mg/kg

Side effect Bradyarrhythmias, Nausea, diarrhea, Most rapid onset of Bradycardia,

bronchospasm, cross frequent urination, action but shortest increased
the placenta -> fetal abdominal pain duration; nausea, tearing, and
bradycardia vomiting,excessive lacrimation
swearing, stomach
cramps
Cholinesterase
Contraindicati Inhibitors
peritonitis, or In cases of Asthma, mechanical Intestinal and
Adrenergic
Pharmacology
Endogenous and Synthetic Catecholamines
Noncatecholamine Sympathomimetic
Amines
Selective Alpha-Adrenergic Receptor
Agonists
Beta2-Adrenergic Receptor Agonists
Alpha-Adrenergic Receptor Antagonists
Beta-Adrenergic Antagonists
1. ENDOGENOUS AND SYNTHETIC
CATECHOLAMINES
NOREPINEPHRINE
• Primary adrenergic neurotransmitter
• Binds to alpha and beta receptors
• Used primarily for its a1-adrenergic eff ects that
increase SVR
• Short half-life (2.5 minutes)
• Usually given as continuous infusion at rates of
3mcg/min

Endogenous and Synthetic

EPINEPHRINE
• Binds to alpha and beta-adrenergic receptors
• Used intravenously in life-threatening circumstances
• Cardiac arrest, circulatory collapse, and anaphylaxis
• Commonly used locally to decrease systemic
absorption of local anesthetics and reduce surgical
blood loss
• Therapeutic eff ects:
• Positive inotropy, chronotropy, and enhanced
conduction (B1)
• Smooth muscle relaxation (blood vessels, bronchi) (B2)
• Vasoconstriction
• Eff ects that predominate depend on dose
Endogenous and Synthetic
EPINEPHRINE
• IV dose of 1 mg – cardiovascular collapse, asystole,
ventricular fi brillation, pulseless activity, anaphylactic
shock
• Continuous1 toinfusion
2 mcg/min – inStimulate
less acute circumstances
B2-receptors
Decrease airway resistance and
vascular tone
2 to 10 mcg/min Increases heart rate, contractility,
and conduction through the AV node
> 10 mcg/min A1-adrenergic effects predominate -
> generalized vasoconstriction ->
reflex bradycardia

Endogenous and Synthetic

DOPAMINE
• Binds to alpha and beta-receptors, + dopaminergic
receptors
• Acts indirectly by stimulating release of NE from storage
vesicles
• Binds to D1 receptors -> improve blood fl ow through renal
and mesenteric
0.5 – 2.0beds in shock-like
D1 receptors arestates
stimulated
• Half life of mcg/kg/min
1 min – must Renal and entericas
be given beds are dilated
continuous
infusion 2 to 10 mcg/kg/min B1 receptors are stimulated
Cardiac contractility and output are
increased
> 10 mcg/min A1-receptor binding predominates
Marked generalized vasoconstriction

Endogenous and Synthetic

ISOPROTERENO
L• Provided relatively pure and nonselective B-adrenergic
stimulation
• B1 > B2
• AE: tachycardia, arrhythmias
• Principal uses:
• Chronotropic drug after cardiac transplantation
• Initiate Afi b or other arrhythmias during cardiac
electrophysiology ablation procedures
• Half life longer than endogenous catecholamines

Endogenous and Synthetic

DOBUTAMINE
• Synthetic analog of dopamine
• Predominantly B—adrenergic eff ects
• Endogenous NE not released; does not act on
dopaminergic receptors
• Potentially useful in CHF or MI patients with low CO

Endogenous and Synthetic

2. NONCATECHOLAMINE SYMPATHOMIMETIC AMINES

• Most noncatecholamine sympathomimetic

amines act at α- and β-receptors through
both direct (binding of the drug by
adrenergic receptors) and indirect
(release of endogenous norepinephrine
stores) activity.
 EPHEDRINE
• Increases arterial blood pressure and has a positive
inotropic eff ect
• Widely used as a pressor in hypotensive pregnant
patients
• Helpful in treating moderate hypotension, particularly if
accompanied by bradycardia
• Usual dose is 2.5 to 10 mg IV or 25 to 50 mg IM .

Noncatecholamine Sympathomimetic
3. SELECTIVE A-ADRENERGIC RECEPTOR
AGONISTS

Alpha1-Adrenergic Alpha2-Adrenergic
Agonists Agonists
Phenylephrine Clonidine
Dexmedetomidine
PHENYLEPHRINE
• a selective α1-agonist
• Frequently used for peripheral vasoconstriction when
cardiac output is adequate
• Also used to maintain afterload in patients with aortic
stenosis whose coronary perfusion is compromised by a
decline in sys- temic vascular resistance.
• IV: rapid onset, short duration of action (5-10 mins)
• Bolus: 40 to 100 μg; infusion: starting at a 10 to 20
μg/min.
• A mydriatic and nasal decongestant.
• Used to prepare the nares for nasotracheal intubation

Selective a-Adrenergic Receptor

CLONIDINE
• Selective agonist for α2-adrenoreceptors
• Has antihypertensive
• Clonidine withdrawal - may precipitate a hypertensive
crisis
• Labetalol is used to treat clonidine withdrawal syndrome.
• Can reduce the requirements for other IV or inhaled
anesthetics as part of a general or regional anesthetic
technique.
• Provide eff ective analgesia for acute and chronic pain,
particularly as adjuncts to local anesthetics and opioids.
Epidural clonidine is indicated for the treatment of
intractable pain
Selective a-Adrenergic Receptor
 4. B2-ADRENERGIC RECEPTOR
AGONISTS

• β2-Agonists are used to treat reactive airway

disease.
• Commonly used agonists include:
• Metaproterenol (Alupent, Metaprel)
• Terbutaline (Brethine, Bricanyl)
• Albuterol (Proventil, Ventolin).
• β2-Agonists are also used to arrest premature
labor
• Ritodrine (Yutopar) has been marketed for this
purpose.
• Unfortunately, β1-adrenergic adverse eff ects are
common, particularly when the drug is given
 ALBUTEROL
• Aka Salbutamol
• Treatment and prevention of bronchospasm (acute or
severe) in patients with reversible obstructive airway
disease, including exercise-induced bronchospasm.
• Acts on beta-2 adrenergic receptors to relax the bronchial
smooth muscle .
• Inhibits the release of immediate
hypersensitivity mediators from cells, especially mast
cells.
• Available as nebulizer solution, aerosol/powdered
metered-dose inhaler, and extended-release tablets

B2-Adrenergic Receptor Agonists

 5. ALPHA-ADRENERGIC RECEPTOR
ANTAGONISTS

• Used as antihypertensive drugs

• Side eff ects: marked orthostatic
hypotension, fl uid retention
PHENOXYBENZAMIN
E• Prototypical α1- adrenergic antagonist (also has α2-
antagonist eff ects).
• Irreversibly binds α1-receptors - new receptors must be
synthesized before complete recovery
• Decreases peripheral resistance, increases cardiac output
• Recommended treatment for a phenoxybenzamine
overdose - infusion of norepinephrine or vasopressin

Alpha-Adrenergic Receptor
PHENOXYBENZAMIN
E• Prototypical α1- adrenergic antagonist (also has α2-
antagonist eff ects).
• Irreversibly binds α1-receptors - new receptors must be
synthesized before complete recovery
• Decreases peripheral resistance, increases cardiac output
• Establishes a “ chemical sympathectomy ”
preoperatively during surgical resection of catecholamine-
secreting tumors (eg. Pheochromocytomas)
• Recommended treatment for a phenoxybenzamine
overdose - infusion of norepinephrine or vasopressin

Alpha-Adrenergic Receptor
PRAZOSIN
• Potent selective α1-blocker that antagonizes the
vasoconstrictor eff ects of norepinephrine and
epinephrine
• Major AE: Orthostatic hypotension is a major problem with
prazosin.
• Improves lipid profi les by lowering low-density lipid
levels and raising the level of high-density lipids
• Usual starting dose : 0.5 to 1 mg given at bedtime

Alpha-Adrenergic Receptor
 6. BETA-RECEPTOR
ANTAGONISTS

• Beta-blockers; frequently used as preoperative

medication
• Clinical indications: ischemic heart disease,
postinfarction management, arrhythmias,
hypertrophic cardiomyopathy, hypertension, heart
failure, migraine prophylaxis, thyrotoxicosis, and
glaucoma
• Most widely used: propranolol, metoprolol,
labetalol, esmolol
• Contraindications: peripheral vascular diseases,
diabetes mellitus, chronic obstructive pulmonary
disease (COPD) and asthma.
 PROPRANOLOL
• the prototypical β-blocker; nonselective
• Extensively metabolized in the liver
• Clearance of the drug can be aff ected by liver disease
or altered hepatic blood fl ow
• Available in an IV form
• Bolus - 0.1 mg/kg may be given, but most practitioners
initiate therapy with much smaller doses, typically 0.25
to 0.5 mg
• Shifts the oxyhemoglobin dissociation curve to the right ,
which might account for its effi cacy in vasospastic
disorders.
• Commonly used in the treatment of hyperthyroidism to
mitigate tachycardia that may result
Beta-Receptor Antagonists
 METOPROLOL
• Cardioselective β-adrenergic blocker
• Approved for the treatment of angina pectoris and
acute myocardial infarction .
• No dosing adjustments are necessary in patients with
liver failure. Usual oral dose: 100 to 200 mg/day QD or
BID for hypertension and BID for angina pectoris.
• IV dose of 2.5 to 5 mg may be administered every 2 to 5
minutes up to a total dose of 15 mg, with titration to
heart rate and blood pressure.

Beta-Receptor Antagonists
 LABETALOL
• Acts as a competitive antagonist at the α1- and β-
adrenergic receptors.
• Metabolized by the liver; clearance is aff ected by hepatic
perfusion.
• May be given intravenously every 5 minutes in 5- to 10-
mg doses or as an infusion of up to 2 mg/min .
• Can be eff ective in the treatment of patients with aortic
dissection and in hypertensive emergencies.
• Has been given to cardiac patients postoperatively
• May be used to treat hypertension in pregnancy both on a
long-term basis and in more acute situations.

Beta-Receptor Antagonists
References
• Bankenahally R, Krovvidi H. Autonomic nervous system:
anatomy, physiology, and relevance in anesthesia. BJA
Education.
• Butterworth JF, Mackey DC, Wasnick JD. Morgan &
Mikhail’s Clinical Anesthesiology. 6e. McGraw Hill
Education; 2018
• Hall JA. Guyton and Hall Textbook of Medical Physiology.
13e. Elsevier; 2016
• Pardo MC, Miller RD. Basics of Anesthesia. 7e. Elsevier;
2018
THANK YOU.