As We Go Along…….

1. Introduction

2. Divisions Of ANS & Functions

GENERAL ORGANISATION AND
3. Organisation
NEUROTRANSMISSION OF THE ANS
4. Neurotransmission Process

5. Higher Levels Of Autonomic Control

Autonomic Nervous System (ANS)

NERVOUS SYSTEM 1. Sympathetic division (thoraco-lumbar, “fight
or flight”) – prepare body for stress and
PERIPHERAL CENTRAL NERVOUS activity
NERVOUS SYTEM SYETM
•Thoracic and lumbar segments
MOTOR SENSORY

DIVISION DIVISION
BRAIN SPINAL
CORD
AUTONOMIC SOMATIC 2. Parasympathetic division (cranio-sacral, “rest
SYSTEM SYSTEM and digest”) – Maintains homeostasis at rest
Sympathetic

Parasympathetic
Organization of 3. Enteric division
Enteric
Nervous System

Organization of the Sympathetic Division The Distribution of Sympathetic Innervation

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Sympathetic Pathways Sympathetic Pathways

Sympathetic Pathways III

PARASYMPATHETIC VII
DIVISION

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The cell bodies are within the
brainstem and sacral region
X

Cranio-sacral division

Parasympathetic Outflow Organization of the Parasympathetic Division

Parasympathetic outflow is through:

1.Cranial nerve (III, VII, IX, X), and
2.Plexuses (vagus and thoracic nerve
plexuses, abdominal nerve plexuses, and
pelvic nerve and pelvic nerve plexuses)

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Distribution of Parasympathetic Innervation

A. Sympathetic reflex

AUTONOMIC REFLEXES

B. Parasympathetic reflex

NEUROTRANSMISSION OF
ANS

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 Regulation Of The ANS
•Neurotransmitters are the chemicals which
1. To maintain homeostasis, the structures
allow the transmission of signals from one
innervated by ANS are regulated through
neuron to the next across synapses.
the autonomic reflexes

2. Input come from cerebrum, hypothalamus,

❖Not reabsorbed by the pre-synaptic neuron
and other area as conscious thoughts and
or broken down into a metabolite (e.g.:-DA,
actions, emotions, and other CNS activities
Serotonin)

Feature Sympathetic Parasympathetic

division division
Location of intermediolateral horns of Brainstem and lateral parts
preganglionic cell Bodies spinal cord gray matter (T1 – of spinal gray matter (S2 –
L2) S4)
Outflow from the CNS Spinal nerves Cranial nerves
Sympathetic nerves Pelvic nerves
Sympathetic vs. Parasympathetic Splanchnic nerves
Ganglia The chain along spinal cord Terminal ganglia near or on
for spinal and sympathetic effector organ
nerves; collateral ganglia for
splanchnic nerves

Number of Many (much divergence) Few (less divergence)

postganglionic neurons
for each preganglionic
neuron
Relative length of Short preganglionic Long preganglionic
neuron Long postganglionic Short postganglionic

The Anatomical Differences ENTERIC NERVOUS SYSTEM

1. Consist of nerve plexuses within the wall of the
digestive tract
2. The plexuses have contributions from three sources:
a. Sensory neurons that connect the digestive tract to
the CNS
b. ANS motor neurons that connect the CNS to the
digestive tract
c. Enteric neurons, which are confined to the enteric
plexus
3. The CNS is capable of monitoring the digestive tract
through sensory neurons and controlling its smooth
muscle and gland through ANS motor neurons

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Higher levels of autonomic control

•Activity in the ANS is controlled by centers

in the brainstem that deal with visceral
functioning

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 Parasympathetic Nervous System
• Works to save energy, aids in digestion,
Autonomic Nervous System and supports restorative, resting body
functions.
Cholinergic Drugs – Decrease in heart rate
– Increased gastro intestinal tract tone and
peristalsis
– Urinary sphincter relaxation
– Vasodilation – decrease in blood pressure

Cholinergic Receptors
Body Responses – “rest and digest” M1 Secretory glands salivation, stomach acid,
sweating, lacrimation

• Dilation of blood vessels in skin M2 Heart Decreases heart rate →

bradycardia
• Decrease heart rate (bradycardia) Contraction of smooth
M3 Smooth muscle
• Increase secretion of digestive enzymes (GI/GU/Resp) muscles (some) → diarrhea,
• Constriction of smooth muscle of bronchi bronchospasm, urination

• Increase in sweat glands - cooling

M3 Pupil and ciliary muscle Contracts → Miosis
• Contraction of smooth muscles of urinary Increased flow of aqueous
bladder humor
• Contraction of smooth muscle of skeletal Nm Skeletal muscle end Contraction of skeletal
system plate muscle

Nn Autonomic ganglia, Secretion of Epinephrine

Adrenal Medulla Controls ANS

Cholinergic Drugs
• Often called parasympathomimetic drugs, because
their action mimics the action of the PSNS.
• Also called as cholinomimetic.
• Stimulate parasympathetic nervous system in same
manner as does acetylcholine.
• May stimulate cholinergic receptors directly or slow
acetylcholine metabolism at synapses (affect the
enzyme acetylcholinesterase)
• Cholinergic agonists are two types :
1. Direct acting
2. Indirect acting

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 Direct acting cholinergic agonist
• They act by binding directly to cholinoceptors. Direct acting Drug Effects of Cholinergic Agents
cholinergics are lipid insoluble.
• Do not readily enter the CNS so effects are peripheral. • Cardiovascular effects
• Resistant to metabolism by acetylcholinesterase. – Decreased heart rate( Bradycardia)
• Effects are longer acting than with acetylcholine.
– Vasodilation (NO mediated)
• Acetylcholine
• Stimulate intestine and bladder
• Methacholine Muscarine
– Increased gastric secretions
• Carbachol Pilocarpine – Increased gastrointestinal motility
– Increased urinary frequency
• Bethanechol Arecoline

Drug Effects of Cholinergic Agents
• Stimulate pupil
– Constriction (miosis), Spasm of accomodation
– Reduced intraocular pressure (increased outflow)
• Respiratory effects
– Bronchial constriction, narrowed airways
• Increased salivation and sweating
Acetylcholine
• One of the main neurotransmitters of the ANS is
acetylcholine
• Acetylcholine is released at preganglionic fibers of
both the sympathetic and parasympathetic nervous
system
• Also released from postganglionic sympathetic
neurons that innervate the sweat glands and from
motor neurons that innervate the skeletal muscles
• It is a quaternary ammonium compound so cannot
penetrate the membrane.
• Does not have any therapeutic importance, because
rapid inactivation by acetylcholinesterases.
• It has both Muscarinic & Nicotinic actions .

Bethanechol Pilocarpine
• Not hydrolyzed by acetylcholinesterases
An alkaloid, lipid soluble & is stable to hydrolysis
• Actions by cholinsterases.
• Directly stimulates M receptors causing increased
intestinal motility & tone Actions:
• It stimulates detrusor muscle of the bladder while When applied locally to cornea Produces rapid
trigone & sphincters are relaxed causing expulsion of miosis & contraction of ciliary muscle produces
urine spasm of accommodation & vision is fixed at
• Therapeutic Uses: particular distance making it impossible to
• Paralytic ileus focus for far situated objects
• Urinary retentions Therapeutic Use : In Glaucoma it opens trabecular
• Helpful for postsurgical atony of the bladder and GI meshwork around schlemm’s canal
tract • causes drainage of aqueous humor
• IOP immediately decreases.

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 Indirect acting Cholinergic agonists
• Reversible: Irreversible:
• They act through inhibition of Acetyl cholinesterase • Neostigmine Organophosphates
enzyme, so increases Acetylcholine level in the • Physostigmine Dyflos,
synapse. Echothiopate
• Pyridostigmine Parathion,
• Accumulation of acetylcholine then occurs which
• Edrophonium
enhances the activation of the nicotinic and
• Tacrine Tabun, Sarin,
muscarinic receptors.
• Donepezil
• Anticholinesterase drugs are either reversible or Carbamates
irreversible inhibitors of acetylcholinesterase Carbaryl,
Propoxur(baygon)

• Physostigmine - only anticholinesterase • Neostigmine - prototype anticholinesterase agent.

capable of crossing the blood brain barrier. Is
more lipid soluble. Used as an antidote for
overdosage of anticholinergics such as:
atropine, antihistamines, TCA, phenothiazines.
May also be used in treatment of glaucoma.
• Pyridostigmine - is the maintenance drug of
choice for patients with Myasthenia gravis.
Used for long-term treatment of myasthenia gravis
and as an antidote for tubocurarine and other non-
depolarizing agents in surgery.
• Donepezil - Used in the treatment of mild to
moderate Alzheimer’s disease.
• Helps to increase or maintain memory and
learning capabilities.

Uses of Indirect Cholinergic agonists • Cobra bite – Edrophonium (prevent

• Glaucoma – Pilocarpine, Physostigmine
• Edrophonium - to test Myasthenia gravis
• Neostigmine and pyridostigmine –in
treatment of M.gravis.
• Postoperative paralytic ileus - Neostigmine
• Postoperative decurarization –
Neostigmine(reverses muscle paralysis)
respiratory paralysis.
• Atropine poisoning – Physostigmine
(antogonizes both central and peripheral
effects).
• Alzheimer’s Disease – Donepezil,
galantamine, tacrine, rivastigmine.
• TCA, Phenothiazines, overdose –
Physostigmine.

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 CholinergicAgents: Side Effects
Side effects are a result of overstimulation
of the PSNS.
• Cardiovascular:
– Bradycardia, hypotension, conduction
abnormalities (AV block and cardiac arrest)
• CNS:
– Headache, dizziness, convulsions
• Gastrointestinal:
– Abdominal cramps, increased secretions,
nausea, vomiting
Mechanism of action
• They bind irreversibly to the active centre of cholinesterase
so preventing the enzyme from hydrolyzing Ach.
• Because of irreversible binding, effects persist until new
molecules of cholinesterase are synthesized.
CholinergicAgents: Side Effects
• Respiratory:
–Increased bronchial secretions,
bronchospasms
• Other:
–Lacrimation, sweating, salivation, loss of
binocular accommodation, miosis
Irreversible cholinesterase inhibitors
• Highly toxic, employed primarily as insecticides.
• They are also developed, to be used in war called as nerve gases but
they are volatile liquids.
• They are organophosphate cholinesterase inhibitors because they
contain an atom of phosphorus.
• They are highly lipid soluble so are readily absorbed from all routes
of administration like skin, GIT & inhalation.
• Once they are absorbed, they have readily access to all tissues &
organs including CNS.
Typical features of acute poisoning
1.GIT-salivation, vomiting, abdominal cramps, diarrhoea,
and involuntary defecation
2.Respiratory system-broncoconstriction, increased
bronchial secretions, cough, wheezing & dyspnoea
3.CVS-bradycardia
4.Genito Urinary Tract-involuntary micturition
5.Skin- sweating
6.Skeletal system- muscle weakness & twitching
7.CNS- miosis, anxiety, headache, convulsions, respiratory
failure
*Death is due to respiratory failure (action in CNS causing respiratory
muscle paralysis) & due to excessive bronchial secretions &
bronchoconstriction.
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Treatment Anticholinergic drugs
1.Contaminated clothes should be removed & skin washed.
2.Atropine 2mg i.m. or i.v.& repeated every 15-60 min until dryness • They are divided into:
of mouth & heart rate exceeding 70 beats/min which indicates
adequate effect.
1. Antimuscarinic drugs(atropine related drugs) act
3.Mechanical ventilation
principally at postganglionic cholinergic (parasympathetic)
4.Diazepam for convulsions nerve endings.
5.Atropine eye drops to relieve headache caused by miosis
6.Enzyme reactivation- pralidoxime reverses poisoning by 2.Antinicotinic drugs:
dissociating organophosphate inhibitors from the active center of
cholinesterase. It is given by a slow i.v injection over 5-10 min. a)Ganglion-blocking drugs
b)Neuromuscular blocking drugs
*Its efficacy is greatest if administered within the first 12 hr of
poisoning, if significant reactivation occurs, muscle power improves
within 30 min. *It cannot cross BBB, so cannot reverse cholinesterase
inhibition in CNS.

I. Antimuscarinic drugs (parasympatholytic

drugs)
A. Atropine (belladonna alkaloid) Is the prototype of this
group, is an alkaloid from the deadly night shade Atropa
belladonna.

Mechanism of action:
• It competitively & selectively blocks muscarinic receptors
at therapeutic doses, but in sufficiently high doses, it
produces some blockade of nicotinic receptors as well.

Pharmacological effects
a. Exocrine glands-all secretions, except milk, are diminished.
• Dry mouth & dry eye are common.
• Gastric acid secretion is reduced as well as the volume of gastric
secretion, so PH is little altered.
• Sweating is inhibited, bronchial secretions are reduced & become
viscid as removal of secretions by cough & ciliary action is rendered
less effective.
b. Smooth muscles:
Relaxed, decreased tone & peristalsis in GIT, bronchodilatation,
decreased micturition & urinary retention may be induced especially in
preexisting prostatic enlargement.
c. Ocular effects :Mydriasis with increased IOP, accommodation for far
vision due to paralysis of ciliary muscle (cycloplegia).
d. CVS: Reduces vagal tone, so causes tachycardia & enhanced
conduction in bundle of His, has no significant effect on peripheral
blood vessels in therapeutic doses but in overdose causes marked
vasodilatation.
e. CNS: Causes mild CNS stimulation at therapeutic doses, in toxic
doses it causes hallucination & delirium, extremely high doses result in
coma, respiratory arrest & death.

*Atropine is readily absorbed from GIT, can be given orally, topically &
injection.

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 Adverse effects:
Clinical uses
• Dry mouth,
1.Preanesthetic medication
• Blurred vision & photophobia,
2.In ophthalmology
• Increased IOP,
3.Bradycardia following myocardial infarction
• Urinary hesitancy or urinary retention,
4.Cholinergic poisoning
• Constipation,

• Anhidrosis (deficiency or absence of sweat) & hyperthermia,

• Thickening & drying of bronchial secretions resulting in bronchial

plugging.

Atropine poisoning
Contraindications
• Is characterized by dry mouth, blurring of vision,
photophobia, hyperthermia, CNS effects(hallucination &
delirium), and hot dry & flushed skin.
1.Glaucoma .

2.Prostatic hypertrophy. *Death results from respiratory depression secondary to

blockade of cholinergic receptors in brain.
3.Patients with tachycardia .

4.Intestinal atony. Treatment

1.minimizing absorption- by syrup of ipecac to induce
vomiting, & activated charcoal to adsorb the poison within
intestine

2.Antidote- physostigmine, because it crosses BBB.

B. Hyoscine (scopolamine)

• Is structurally close relative to atropine.

C. Hyoscine butylbromide (Buscopan)
*The main difference:

a. is CNS depressant, causes confusion esp. in elderly ➢Also blocks autonomic ganglia.

b. mydriasis is briefer than atropine ➢If injected, it is effective relaxant of smooth muscles including
cardia, pyloric antral region & colon. So is useful in colic &
c. suppresses emesis& motion sickness endoscopy.

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D. Homatropine
Is used as eye drops , its action is shorter than atropine, so
less likely to cause serious increased IOP, the effect wears off
in a day or two.
E. Tropicamide (Mydriacyl) & Cyclopentolate (Mydrilate)
Used as eye drops for mydriasis & cycloplegia, are quicker &
shorter acting than homatropine, produce mydriasis within
10-20min & duration of action is 4-12h
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F. Ipratropium (Atrovent)
➢ Is used as an inhaled bronchodilator for acute bronchial
asthma & chronic obstructive pulmonary disease.
G. Flavoxate (Uripas) & Oxybutynin (Cystrin)
➢ Is used for urinary frequency, tenesmus, and urgency
incontinence because it increases bladder capacity &
reduces unstable detrusor contractions.
H. Propantheline (Pro-Banthine)
➢Is used as smooth muscle relaxant e.g. in irritable bowel
syndrome & diagnostic procedures.
I. Benzhexol & Orphenadrine used in parkinsonism.
J. Promethazine is used as an antiemetic.
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