Autonomic Nervous System (ANS) Pharmacology

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Nervous System (N.S)
Central Nervous System (C.N.S)
Brain Spinal Cord
Peripheral Nervous System (P.N.S)
Sensory Division
(Afferent Division)
Autonomic Sensory
Division
Somatic Sensory
Division
Motor Division
(Efferent Division)
Autonomic Motor
Division
Sympathetic Division
Parasympathetic Division
Enteric Division
Somatic Motor
Division

2. The Autonomic Nervous System (A.N.S)
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Parasympathetic
Symp.
Somatic
4 PN
A.Ch. A.Ch. M
NR
Preganglionic Post
A.Ch NE α 
NR 20 postganglionic neuron Ach
Except adrenal medulla (no ganglia)  modified postganglionic
A.Ch.
NM
Brain
Spinal
Cord
Sk.m.
Autonomic Nerves and Somatic System

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The autonomic nerves The Somatic nerve
❶. It controls involuntary function
(Viscera, glands, heart and blood vessels).
❶. It controls the voluntary functions.
❷. The autonomic nerves don’t travel
directly from CNS to the effector organ →
But, it relays in synapses (Autonomic
ganglia) outside the CNS.
❷. The somatic nerve travels directly from
the CNS to the skeletal muscles without the
mediation ganglia.
❸. The autonomic nerve is composed of
two neurons → Preganglionic neuron
(Myelinated) and Postganglionic neuron
(Non-myelinated).
❸. Somatic nerve is composed of Only one
myelinated neuron (No ganglia).

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Division of the ANS

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Division of the ANS
Parasympathetic nervous system Sympathetic nervous system
Origin:
Cranio-sacral
Originate from cranial nerves:
Thoracolumbar
These arises from thoracic (T1 –
T12) and lumbar (L1 – L3)
segments of the spinal cord.
❶. 3rd  Occulomotor nerve.
❷. 7th  Facial nerve.
❸. 9th  Glossopharyngeal nerve.
❹. 10th  Vagus nerve (80 – 90%).
❺. Sacral segment (S2 – S4) in spinal cord.
Functions:
REST & DIGEST FIGHT, FRIGHT &FLIGHT
❶. Conserving energy so ↓ metabolism. ❶. Utilizing energy
❷. Maintain essential body functions.
❷. Responsible for stress
condition.
❸. Essential for survival. ❸. Not essential for survival.

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Ganglia:
Usually terminal or embedded in
organ (Faraway from spinal
cord).
Near spinal cord.
Pre-ganglionic: Long. Short.
Post-ganglionic: Short. Long.
Chemical
Transmitter in
pre ganglionic
neurons:
Acetylcholine (A.Ch.)
(Cholinergic).
Acetylcholine (ACh)
(Cholinergic)
Branching of pre-
ganglionic fibers:
Minimal. Extensive.
Chemical Transmitter
in
Post- ganglionic
neurons:
A.Ch
Noradrenaline (NE) → Adrenergic
EXCEPT:
❶. Adrenal medulla → A.Ch.
❷. Blood vessels of some Skeletal muscles → A.Ch.
❸. Sweat glands in the most body regions (Eccrine) →
A.Ch.
❹. Blood vessels of kidney  dopamine and NE.

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Distribution: Limited. Wide.
Type of
response:
Discrete. Diffuse.

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Sites of Ach release
❶. All preganglionic autonomic ganglia
(For both Sympathetic & Parasympathetic).
❷. All postganglionic parasympathetic nerve endings.
❸. Somatic nerve of skeletal muscle (End Motor Plate)
(Neuromuscular junction) (NMJ).
❹. Exceptions: Sympathetic nerve to
Sweat glands,
Adrenal medulla and
B.V.’s of some Skeletal muscles.

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Effect of sympathetic and parasympathetic on major body
organs

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Dual innervations by the autonomic nervous system
Most organs in the body are innervated by both divisions (Sympathetic &
parasympathetic) but, one system usually predominates (Vagus nerve in
heart).
❷. Sympathetic and parasympathetic systems have opposing actions
(Physiological antagonist) in most situations e.g. (Control of heart, GIT).
N.B: But, in the salivary glands the effects of sympathetic and
parasympathetic are similar (↑ Salivary secretion).
Parasympathetic stimulation ↑ Watery saliva whereas
sympathetic stimulation ↑ Secretion of mucinous saliva.

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Single
innervated
organs
Organs/Tissues
receiving only
Sympathetic
innervation
Iris radial (Dilator) pupillae muscle
Pilomotor smooth (Erector pili) muscle
Blood vessels of peripheral circulation EXCEPT
Vessels in vicesra and brain.
Ventricles of heart
Kidney (Juxtaglomerular cells and arterioles)
Spleen
Adipose tissue
Seminal vescieles
Organs innervated only
by sympathetic neurons
which release Ach:
Arterioles of some
skeletal muscles
Adrenal
medulla
Sweat
glands
Organs/Tissues
receiving only
Parasympathetic
innervation
Iris sphincter
(Constrictor)
pupillae muscle
Ciliary muscle of the eye
Bronchular smooth muscle
Arterioles of the erectile
tissue of sex organ

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Autonomic drug receptors

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Sympathetic nervous system
Sympathetic acting drugs
Adrenergic receptors:
 Are classified into Alpha (α) and Beta (β) adrenergic receptors.
Alpha (α) adrenoceptors
Subtype Actions
α1 receptors
(Post synaptic membrane of
the effector organs)
All α1 receptors are excitatory
(leads to contraction) EXCEPT on
GIT (is inhibitory).
 Gq  phospholipase C
(PLC)  ↑ IP3 +
↑ DAG ↑ Ca2+
influx + ↑ Ca2+
released from
intracellular
stores 
Vascular smooth
muscle
contraction
 VC of blood vessels
 CONTRACT radial muscle
mydriasis
 Contraction of sphincter
(GIT)
 Relaxation of non-sphincter
parts (GIT)
 Glycogenolysis &

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Actions of α2
adrenoceptors
C.N.S Presynaptically Platelets G.I.T
Pancreatic
β cells
α2 receptors are coupled to Gi protein  ↓ Activity of Adenylate cyclase  ↓
Formation of cAMP ↓ Presynaptic NE synthesis and release  ↓ Sympathetic outflow.

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2) Beta receptors
All β receptors are coupled to Gs protein  ↑ A.C.  ↑ c AMP
Actions of β1 adrenoceptors
Heart
→
↑ Heart Rate (HR).
→
↑ Force of contraction.
→
↑ Atrioventricular conductivity (A.V).
↑ Excitability.
Kidney
↑ Renin
release
Presynaptically
↑ NE
release

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Actions of β2 adrenoceptors
Smooth muscle
Relaxation
B.V of coronary
and skeletal
muscles
Skeletal muscles
Muscular
Liver
Hepatic
G.I.T
of G.I.T wall

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Actions of β2 adrenoceptors (Con't)
Mast
cells
Bronchi
through action
of circulating E on β2 receptors of
bronchi (No sympathetic
innervation)
Urinary bladder
of detrusor
muscle
Uterus of non-pregnant
women (β2)

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β3 receptors
in the adipose tissue stimulate the lipolysis and thermogenesis processes.

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Neurotransmission at A.N.S
Cholinergic neurons

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1)Synthesis ………………….
2)Storage ………………..
3)Release ………………….
4)Binding ……………………………
5)Degradation of acetylcholine
 Two types of cholinesterase
1)Acetylcholinesterase (AChE) (True) RBCs
2)Butyrylcholinesterase (BChE) (Pseudocholinesterase)Liver,
skin ,brain &GIT
Closely related in molecular structure but differing in their
distribution substrate specificity and functions.
 AChE very efficiently splits Ach into choline and acetate
6) Recycling………………………………………….

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Adrenergic neurons

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The mechanisms of termination of the adrenergic action
❶. Types of the adrenergic uptake mechanisms:
Uptake 1 Uptake 2 Uptake 3
Neuronal uptake. Tissue (Extra-neuronal) uptake. Granular (Vesicular) uptake.
The most important terminating
mechanism of adrenergic
action:
Uptake of NE from the
extracellular fluid to the
Via
→
cytoplasm of neuron
dependent NE
-
/Cl
+
Na
.
transporter (NET)
Uptake of catecholamines from
the extracellular fluid to →
smooth
,
Cardiac muscle
blood
and
muscle of intestine
.
vessels
Uptake of NE from the
extracellular fluid to the
cytoplasm of neuron → To be
actively transported into its
.
presynaptic storage vesicles
TCAs, SNRIs, cocaine and
guanethidine → Blockade of
NET → ↑ NE conc. at the
receptor site.
Reserpine.

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❷. Types of the enzymatic degradation mechanisms
MAO COMT
Mono-Amine Oxidase enzyme. Catechol-O-Methyl Transferase enzyme.
captured
-
re
of
Oxidative amination
(NE,
nerve endings
in the
catecholamines
Dopamine and serotonin).
in
catecholamines
released
of
Methylation
methoxy
-
3
-
hydroxy
-
4
HMMA (
→
to
synapses
mandelic acid) (Vinylmandelic acid) (VMA) →
To be excreted into urine.
neuronal mitochondria in the
Present in
.
nerve terminals
.
synaptic cleft
Present in
is a very important
Urinary VMA level
diagnostic test for pheochromocytoma → Due
to severe ↑↑ NE and E → ↑↑ VMA levels.

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Baroreceptor reflex arch

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Renin angiotensin aldosterone system

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 Iris radial pupillae muscle (Dilator muscle):
❶. This muscle is primarily controlled by → Sympathetic nervous system. Activation of
α1 adrenoceptors → Cause contraction of the dilator muscle → ↑ Pupil Size
(Mydriasis).
❷. This action is very beneficial for the fundus examination → Upon the administration of
α agonist (Phenylephrine) in the conjunctival sac → Cause Active mydriasis.
 Iris constrictor pupillae muscle (Sphincter or circular muscle):
❶. This muscle is primarily controlled by → Parasympathetic nervous system from the
oculomotor nerve. Activation of M3 cholinoceptors → Cause contraction of the
constrictor muscle → ↓ Pupil Size (Miosis).
❷. when block M receptor (Atropine)  Paralysis of circular muscle 
relaxation  mydriasis (passive)

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 Note: The difference between
Active mydriasis Passive mydriasis
By Activation of α1 receptors on the
dilator pupillae muscle of the eye.
By Blocking M3 receptors on the
constrictor pupillae muscle of the eye.
By administration of α agonist →
Phenylephrine.
By administration of Muscarinic
antagonist → Atropine.
Ciliary muscle:
❶. This muscle is primarily controlled by → Parasympathetic
nervous system → By the activation of M3 cholinoceptors:

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Accommodation (controlled by ciliary muscle which is parasympathetic
predominate)
 Contraction of ciliary muscle and relaxation of suspensory ligament
lens become thick  Accommodation for near vision (as Ach )
 The ciliary muscle relax away from the lens pulls the ligament
pulls lens  thin lens  accommodation for far vision
 So when block M receptor (by atropine)  Paralysis of ciliary muscle
 Contraction of suspensory ligament  cycloplegia  loss of
accommodation.

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