Parasympathetic Nervous

System
dr. Bayu Lestari, M. Biomed

Laboratory of Pharmacology
Faculty of Medicine Universitas Brawijaya
2017
Why Study the Autonomic Nervous System?

Pathophysiology Medicinal
Chemistry

Therapeutics ANS Pharmacology

Disease State
Management
 Peripheral Nervous System

Somatic Nervous Autonomic Nervous

System System

Parasympathetic Sympathetic
Nervous System Nervous System

Selective Diffuse
Activation Activation
Skeletal
Glands, Smooth Muscle
Muscle
& Cardiac Muscle
 Peripheral Nervous System
Controls
Controls smooth &
skeletal cardiac
muscle muscle &
glands
Somatic
Nervous Autonomic
System Nervous
System

One Two
Neuron Neuron
Efferent Efferent
Limb Limb
 Somatic
Motor Fiber Skeletal
Ach Muscle
Sympathetic Ganglion Postganglionic Fiber; Smooth Muscle
Adrenergic Cardiac Cells
Ach NE
Gland Cells
Sympathetic Ganglion
Sweat
Ach Ach
Glands
Sympathetic
EPI/NE
Ach
Adrenal Gland
Para-
sympathetic Ganglion Smooth Muscle
Ach Ach Cardiac Cells
Gland Cells
 Radial Muscle of Iris
Sympathetic Nervous System Ciliary Muscle
(Thoracolumbar Outflow) Sublingual/Submaxillary
& Parotid Gland
SA & AV Nodes
Pilomotor Muscles His-Purkinje System
Sweat Glands Myocardium
Bronchi/Bronchial
Glands
Stomach

Blood Vessels Kidneys

Intestines
Paravertebral Ganglia
Bladder//Genitalia
Prevertebral Ganglia
 ADRENAL MEDULLA

Chromaffin Cells

Epinephrine
(+) Dilates Airways (+) Mental Alertness

(+) ACTH & TSH

(+) Cardiac Output

(+) Muscle Contraction & Efficiency (+) Glycogenolysis

(+) Fatty Acid Release (-) Intestinal Motility

 Parasympathetic Nervous System (Craniosacral Outflow)

SA & AV Node Bronchi/Bronchial

Sphincter Muscle of Iris Glands
Ciliary Muscle Stomach

Small Intestines
Lacrimal Gland
Bile Ducts
Gallbladder

Submaxillary & Kidney

Sublingual
Glands Large Intestines

Bladder
Parotid Gland
Genitalia
Most organs receive dual sympathetic
and parasympathetic innervation.

However, some organs only receive

sympathetic innervation:
Spleen
Sweat Glands
Piloerector Muscles
Most Blood Vessels
Parasympathetic Ganglionic Synapse

Acetylcholinesterase

Na+

ACH

aba
Action Potential
Nicotinic
Receptor
Na+

Preganglionic neuron Postganglionic neuron

 Parasympathetic Organ Synapse
Acetylcholinesterase

Effector
Organ
Na+
K+
G
Action Potential
ACH
Muscarinic
Receptor

Postganglionic neuron
Summary of parasympathetic neurons and synapses
Preganglionic neurons
• Long
• Synapse with postganglionic neurons at or near organ
• Release acetylcholine (ACH) to activate nicotinic receptors on
postganglionic neurons

Postganglionic neurons
• Short
• Synapse on the target organ
• Release acetylcholine (ACH) to activate muscarinic receptors on
the target organ
How do drugs influence the ANS?

• Mimic or block the effects of the primary neurotransmitters,

Acetylcholine

• Drugs that mimic neurotransmitters are referred to as “receptor

agonists”
 These drugs activate receptors

• Drugs that block neurotransmitters are referred to as “receptor

antagonists”
 These drugs block the endogenous neurotransmitters from
activating receptors
Classification of drugs affecting the parasympathetic

Mimic acetylcholine = cholinergic = muscarinic agonists =

parasympathomimetic

Block acetylcholine = anticholinergic = muscarinic antagonist

= parasympatholytic
Parasympathetic Effects
• Normally not activated as a whole
Stimulation of separate parasympathetic nerves.
• Release ACh as NT
• Relaxing effects-
Decreases HR (Heart Rate).
Dilates visceral blood vessels.
Increases digestive activity.
Parasympathetic Effects

• Bronchonstriction
• GI motility increases
• Relaxation of sphincters
• Contraction of
Detrusor muscle
Ciliary muscle
• Miosis
Responses to Cholinergic Stimulation

• Cholinergic fibers-.
Release ACh as NT
All somatic motor neurons,
 All preganglionic neurons
 Most postganglionic parasympathetic neurons
 Some postganglionic sympathetic neurons
Responses to Cholinergic Stimulation

•Somatic motor • Excitatory

neurons
•All preganglionic • Excitatory
autonomic
neurons
•Postganglionic • Excitatory or Inhibitory
axons
Responses to Cholinergic Stimulation

.
• Muscarinic receptors
Ach binds to receptor
Requires the mediation of G-proteins
bg-complex affects-
 Opening a channel or
 Closing a channel or
Activating enzymes
Responses to Cholinergic Stimulation

• Nicotinic receptors (ligand -gated)

ACh binds to 2 nicotinic receptor binding sites.
Causes ion channel to open within the receptor protein.
Opens a Na+ channel.
• Always excitatory
Responses to Cholinergic Stimulation
Organs With Dual Innervations

• Antagonistic :
• Sympathetic and parasympathetic fibers innervate the same cells.
• Actions counteract each other.
• Heart rate.
• Complementary:
• Sympathetic and parasympathetic stimulation produces similar effects.
• Salivary gland secretion.
• Cooperative:
• Sympathetic and parasympathetic stimulation produce different effects that
work together to produce desired effect.
• Micturition.
Acetylcholine (Cholinergic)
Receptor Subtypes
Description

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Acetylcholine (Cholinergic) Receptor Subtypes
Description

• Acetylcholinergic receptors subtypes include

• Nicotinic N receptors in the ganglion between the preganglionic neuron and
the postganglionic neuron in the autonomic nervous system
• Muscarinic receptors at the effector organ in the parasympathetic nervous
system and the sweat glands of the sympathetic nervous system
• Nicotinic M receptors at the muscle in the somatic motor system

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Acetylcholine (Cholinergic)
Receptor Subtypes
Chart

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 Acetylcholine (Cholinergic) Receptor Subtypes Chart
Location Response to agonist

Nicotinic (neuronal) NN

On the postganglionic neurons of the Stimulation of post-ganglionic sympathetic or

autonomic system parasympathetic transmission. Stimulation of
epinephrine & norepinephrine release from adrenal
medulla.
Nicotinic (skeletal muscle) NM
On the skeletal muscle cells in the Skeletal muscle contraction
neuromuscular junction
Muscarinic – in parasympathetic nervous
system
Heart, SA node Decreased heart rate (negative chronotropic)

Heart, AV node Decreased speed of conduction (negative dromotropic)

Bronchioles Bronchiolar constriction and increased secretion

Bladder Constriction (micturition)

GI tract Increased motility and increased secretions 30

Adapted from Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 114.
Muscarinic Agonists

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Muscarinic Agonists

•These drugs are not used systemically very often since they have
multiple unpleasant effects.
•Ex. micturition, increased secretions and motility, bronchiolar
constriction

•Pilocarpine
•A muscarinic agonist that is used as an eye drop for glaucoma.

•Bethanecol
•A muscarinic agonist that is used for urinary retention but not
very often
•Can be used orally for dry mouth.
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Muscarinic Antagonists

33
Muscarinic Antagonists
• These drugs are frequently referred to as “anticholinergic” – a misnomer.
• This is a misnomer because it only blocks muscarinic receptors, in the effector
organs in the parasympathetic nervous system and sweat glands of the
sympathetic nervous system, not all cholinergic receptors
• Peripheral side effects
– Can’t see: Relaxation dilates pupil, Dry eyes
– Can’t pee: Constricts bladder sphincter
– Can’t spit: Dries up mouth
– Can’t shit (defecate): Stop GI secretions and motility
• In the brain
• Also can cause confusion and/or delirium.
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Uses of Muscarinic
Antagonists

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Uses of Muscarinic Antagonists
• Used to dry up secretions preoperatively
• Dilate pupils (eye drops)
• Speed up the heart or ameliorate a heart block
• They were previously used as anti-diarrheas.
• (Relate these uses to activity of the parasympathetic nervous system
at muscarinic receptors)

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Types of Muscarinic
Antagonists

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Clinical Use of Muscarinic Antagonists
• Atropine  organophosphate poisoning, bradycardia
• Scopolamine, hyoscine  used for motion sickness, spasmolytic of
smooth muscle
• Glycopyrolate  used for anti-secretory preoperatively
• Ipatropium, Tiotropium  fos asthma and COPD as bronchodilator
• Trihexyphenidil  reverse Parkinsonism
• Tropicamide  midriaticum for eye examination
• Oxybutinin  treat urinary retention

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Cholinergic Crisis (Organophosphate Intoxication)
• Cholinergic crisis occurs when the muscarinic receptors are activated too much
• Ex. Organophosphate intoxication (decrease of Ach-esterase activity)
• Respond by giving muscarinic antagonist like atropine
• Leads to SLUDGE symptoms (Salivation, Lacrimation, Urination, Defecation, GI stress, Emesis)
caused by activity of acetylcholine on muscarinic receptors of the parasympathetic nervous
system.
• CNS depression – coma, stupor, confusion – caused by activity of acetylcholine on muscarinic or
nicotinic receptors in the brain.
• Muscle symptoms – fasciculations, fatigue, spasm – caused by activity of acetylcholine on the
nicotinic skeletal muscle receptors.
• Due to nicotinic receptors on muscles

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 Atropine for Bradycardia or Heart Block
•Cause of Bradycardia and Heart Block
•Acetylcholine from parasympathetic nerve terminals binds to muscarinic receptors in the SA
node and AV node and blocks them
•In the SA node, this slows the heart rate (negative chronotropic effect)
•In the AV node, this slows the speed of conduction (negative dromotropic effect).
•Role of Atropine
•Atropine blocks the effects of acetylcholine at muscarinic receptors, speeding the HR and
speeding conduction through the AV node.
•Atropine may reverse bradycardia by removing the parasympathetic influence.
•May speed conduction in the AV node in heart block.
•This only works if parasympathetic stimulation is important in causing the bradycardia or heart
block.

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Muscarinic Antagonists for Urinary Incontinence

•Sometimes due to irritable bladder

•Irritable bladder occurs when the parasympathetic centers in the sacral cord
respond too vigorously to a small amount of bladder stretch by initiating
micturition.
•The motor portion of this reflex is mediated by muscarinic receptors.
•Several antimuscarinic drugs (oxybutynin [Ditropan®] and tolterodine [Detrol®]) are
marketed to ameliorate this problem.
•Multiple side effects common to muscarinic antagonists

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