THE AUTONOMIC NERVOUS

SYSTEM
 NS
CNS PNS

SC BRAIN ANS SNS

 ANS

• The ANS is predominantly an efferent

system transmitting impulses from the
Central Nervous System (CNS) to
peripheral organ systems
 FUNCTIONS OF THE ANS
• Regulation of heart rate and force of
contraction

• Constriction and dilatation of blood vessels

• Contraction and relaxation of smooth

muscle in various organs*

• Visual accommodation, pupillary size and

secretions from exocrine and endocrine
glands
 BASIC ANATOMY OF THE ANS

AUTONOMIC
NERVOUS SYSTEM

Parasympathetic Sympathetic Enteric

NS NS NS
 BASIC ANATOMY OF THE ANS

• Enteric NS: consists of intrinsic nerve

plexuses in the GIT mainly regulating
GIT function
 BASIC ANATOMY OF THE ANS
SYMPATHETIC NS PARASYMPATHETIC NS
Preganglionic neuron Preganglionic neuron
Short Long
Postganglionic neuron Postganglionic neuron
Long Short
Preganglionic neuron Preganglionic neuron
originates in the thoracic leaves the brain and
and lumbar segments of the spinal cord at the
the spinal cord (T1-L3)- cranial (3rd, 7th ,9th
THORACOLUMBAR 10th nerves) and sacral
OUTFLOW levels –
CRANIO-SACRAL
OUTFLOW
 BASIC ANATOMY OF THE ANS
SYMPATHETIC NS PARASYMPATHETIC NS
Preganglionic neuron Preganglionic neuron
branches and makes makes synaptic contact
synaptic contact at with only 1
ganglia outside of the SC postganglionic neuron.
with ≈ 20 post The only exception
postganglionic fibers. being the GIT with 1:
8000 ratio
Neurotransmitter Neurotransmitter
released at ganglia is released at ganglia is
(Acetylcholine) Ach Ach
Neurotransmitter Neurotransmitter
released at end organ is released at end organ is
Noradrenaline (NA) and Ach
at the adrenal medulla
(adrenaline)
 BASIC ANATOMY OF THE ANS
SYMPATHETIC NS PARASYMPATHETIC NS

End organ response End organ response

achieved via achieved via
ADRENERGIC CHOLINERGIC
RECEPTORS RECEPTORS
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION

• Transfer of information from the

preganglionic to the postganglionic neuron or
from the postganglionic neuron to the
effector organ involves the chemical
transmission of nerve impulses.

End organ

Preganglionic neuron Postganglionic neuron

synapse Neuroeffector
junction
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION
• Information is conveyed via the release of a
chemical mediator called a “neurotransmitter”.
The neurotransmitter is either released by: (a)
the preganglionic neuron and diffuses across
the synaptic cleft to interact with receptors on
the postganglionic neuron or (b) The
postganglionic neuron and diffuses across the
neuroeffector junction to interact with
receptors on the effector organ. End organ

Preganglionic neuron Postganglionic neuron …

…
…
Neuroeffector
synapse junction
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION
This transmission process involves several
steps:
1. Arrival of nerve impulse in the form of an
Action potential (AP) at the nerve terminal of
the preganglionic neuron

Presynaptic Postsynaptic neuron

neuron

AP
Nicotinic
cholinergic
receptor
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION
2. Synthesis of neurotransmitter in the
terminal
3. Storage of the neurotransmitter in the
storage vesicles
Presynaptic
neuron Postsynaptic neuron

oooo
oooo
oooo
AP
 Fig. 2 BIOSYNTHESIS AND METABOLISM OF ACH

Choline acetyl
Nerve terminal
transferase
Choline + Acetyl Coenzyme A ----------------------------------→ Ach + Coenzyme A
←

--------→
←
←
← Acetylcholinesterase
←
←
← Synapse
←
←
←
←
←
←
←
←
Choline Acetic acid
 Fig. 1 BIOSYNTHESIS AND METABOLISM OF
NORADRENALINE
Tyrosine
Tyrosine hydroxylase

3,4 –Dihydroxy-phenylalanine (DOPA)

Metabolism
 Dopa decarboxylase

Dopamine
MAO
 Dopamine-β-hydroxylase
Noradrenaline sympathetic nerve terminal)
►


COMT Phenethanolamine-N-methyl transferase

Adrenaline (adrenal medulla)

MAO - Mono Amine Oxidase

COMT- Cathecol-O-Methyltransferase
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION
4. Release of neurotransmitter into the synapse.
[mobilization and fusion of vesicles involve
specific proteins. These are vesicular proteins
(synaptobrevin & synaptotagmin) found in the
membrane of the vesicle and plasma proteins
(neurexin & synaxin) found in the terminal
membrane]
Ca2+ dependent
Presynaptic Postsynaptic
exocytosis
neuron neuron

oooo oooooo

Ca 2+ Synapse
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION
5. Binding of the neurotransmitter (Ach) to the
nicotinic cholinergic receptor at synapse of
autonomic ganglia
exocytosis
Postsynaptic
Presynaptic
neuron
neuron
SYNAPSE
Na+ K+
oooo ooooooooooooo

Nicotinic
cholinergic
receptor

Fast EPSP
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION
6. Termination of neurotransmitter action via
Acetylcholinetserase (ACHE).

Presynaptic Postsynaptic
neuron neuron

oooo ooooooooooooo

ACHE

choline acetate
AUTONOMIC NEUROCHEMICAL TRANSMISSION:

7.PARASYMPATHETIC/CHOLINERGIC TRANSMISSION:
from the synapse, AP is propagated to the dendrites
of the postsynaptic neuron at the neuroeffector junctio
release of Ach which binds to
muscarinic cholinergic receptors on the effector
organ producing an effect.

Postganglionic
neuron
M EFFECTOR
Ach oo ooo ORGAN
oo
oo ooo
oo
oo ooo
o o
oo

Neuroeffector junction
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION:
7.PARASYMPATHETIC/CHOLINERGIC TRANSMISSION:

CHOLINERGIC RECEPTORS

NICOTINIC MUSCARINIC
(skeletal muscles*and at
Autonomic ganglia)
M3
M1 M2 Gastric gland
Heart
CNS GIT Salivary gland
Gastric gland CNS Eye
Salivary gland GIT
Blood vessels
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION:
7.PARASYMPATHETIC/CHOLINERGIC TRANSMISSION:

Termination of ACH action at the neuroeffector

junction
Postganglionic
neuron

M EFFECTOR
oo
oo ooooo ORGAN
o o o o oooo
o o
oooo o

Neuroeffector junction
AUTONOMIC NEUROCHEMICAL TRANSMISSION:

8. SYMPATHETIC/ADRENERGIC TRANSMISSION:
from the synapse, AP is propagated to the dendrites
of the postsynaptic neuron at the neuroeffector junctio
release of Noradrenaline (NA) which binds to
adrenergic receptors on the effector organ producing
an effect.
Postganglionic
neuron
i ne A EFFECTOR
na l ooo
ra dre o o o o o ORGAN
No o o o
o
oo
oo ooo
o o
oo

Neuroeffector junction
 AUTONOMIC NEUROCHEMICAL
TRANSMISSION:
8.SYMPATHETIC/ADRENERGIC TRANSMISSION:

ADRENERGIC RECEPTORS

BETA-ADRENERGIC ALPHA-ADRENERGIC

β1 β2 α1 α2
Heart Blood vessels Blood vessels Blood vessels
Salivary gland Bronchi Bronchi GIT
GIT GIT Pancreas
Uterus Uterus
Bladder Bladder
Iris Iris
Ciliary muscle
CLASSIFICATION OF DRUGS THAT AFFECT
CARDIAC FUNCTION
1. DRUGS THAT DIRECTLY AFFECT MYOCARDIAL CELLS:
• Autonomic neurotransmitters and related drugs
• Antiarrythmic drugs
• Cardiac glycosides and other ionotropic drugs
• Miscellaneous/endogenous agents

2. DRUGS THAT AFFECT CARDIAC FUNCTION INDIRECTLY:

Anti-anginal agents
Diuretics
ACE inhibitors

3. CALCIUM ANTAGONISTS: direct action on myocardial

cells and indirectly by relaxing arterioles
EFFECTS OF AUTONOMIC
DRUGS ON
THE HEART
 EFFECTS OF SYMPATHETIC ACTIVITY
ON THE HEART

 Positive ionotropic effect

 Positive chronotropic effect

 ↑ automaticity

 Repolarisation

 Reduced cardiac efficiency

 ß1 AGONISTS/ANTAGONISTS

• Sympathetic effects on the heart result

from activation of ß1 receptors by
noradrenaline

• Selective ß1 agonist drugs: Dobutamine:

used for cardiac resuscitation
 ATP
↑ Ca influx
2+

+ Phosphorylation into cell

ß1 AC of Ca 2+ channels
→ opening

Camp PKA

Increased contractile sensitivity via

phosphorylation of troponin C
 CLINICAL USES OF BETA BLOCKERS

• ß1 antagonist: atenolol for hypertension, angina

pectoris. SE=cardiac depression

• NON-selective: propanolol for all the above +

cardiac arrythmias
 PROPANOLOL
• Non selective β-antagonist

• Used for angina*, hypertension, arrhythmias,

glaucoma

• Side effects: bronchiconstriction, cardiac failure,

fatigue and depression

• ROA: op

• Half life= 4 hours, high first pass metabolism

EFFECTS OF PARASYMPATHETIC ACTIVITY
ON THE HEART

 negative ionotropic effect

 negative chronotropic effect

  automaticity

 ↑ AV conduction time → AV block

 AC inhibited→  cAMP

M2  Ca2+
conductance

↑ K+
conductance
 EFFECT OF THE SYMPATHETIC NERVOUS
SYSTEM ON BV/BP

• Receptors on blood vessels: α1 α2 ß2

• α1: vasoconstriction→ PLC →IP3 →↑Ca2+→activates

MLCK

• α2: very few on BV so no effect on BP

• ß2: vasodilation→ AC → ↑cAMP→ inactivates MLCK

Net effect is an increase in blood pressure
 EFFECTS OF SYMPATHETIC DRUGS ON
BP

• Selective α1 agonist: phenylephrine

• Selective α2 agonist: clonidine cause fall in BP

• Selective α2 antagonist: yohimbine

• Selective α1 antagonist: prazosin for hypertension

• Selective ß2 agonist: salbutamol

• B antagonist: propanolol for

hypertension
 EFFECT OF THE PARASYMPATHETIC
NERVOUS SYSTEM ON BV/BP

• M3 receptors on the vasculature

respond to cholinergic drugs and
circulating Ach

• VASODILATION and reduction in BP

OTHER DRUGS AFFECTING
CARDIAC FUNCTION
 CARDIAC GLYCOSIDES

• Extracted from the foxglove plant (Digitalis spp.)

• Main drug in this class is digoxin

• Digoxin acts mainly on the heart and is used in the

treatment of congestive cardiac failure (CCF).

• CCF: failure of the heart to provide sufficient

cardiac output to meet the physiological needs of
the body
 CARDIAC GLYCOSIDES

• CCF: pumping action of ventricles is impaired resulting

in back pressure of blood, with congestion of the lungs
and liver, and swelling of legs
 CARDIAC GLYCOSIDES
• IN CCF digoxin:

• ↑ force of contraction of the heart

MOA:
• binds to Na+/K+ ATPase pump and inhibits it
• Increases intracellular Na+ concentrations
resulting in increased intracellular Ca2+
concentrations
• Increased intracellular calcium concentration
results in increased storage in the sarcoplasmic
reticulum, which increases the FOC
 CARDIAC GLYCOSIDES
• Digoxin also slows AV conduction allowing for
improved ventricular filling in CCF. Also useful
in Supraventricular tachycardia
 CARDIAC GLYCOSIDES

• Digoxin given op or iv

• Half life=36 hrs

• Interactions with amiodarone, verapamil

• Side effects: hypokalemia*, abdominal

discomfort, nausea and vomiting