Download File - Wk 1-2

Autonomic Nervous System Pharmacology
1. Describe the anatomical differences in the sympathetic and
parasympathetic nervous system.
CNS


Brain & spinal cord
Integrative and control centre
PNS


Cranial and spinal nerves
Communication between CNS and the rest of
the body
Motor (efferent) division
Sensory (afferent) division




Somatic & visceral sensory nerve fibres
Conducts impulses from receptors to
the CNS
Motor nerve fibres
Conducts impulses from CNS to
effectors (muscles & glands)
Autonomic Nervous System


Somatic Nervous System
Involuntary (visceral motor)
Conducts impulses from CNS to
cardiac mm, smooth mm & glands
Sympathetic division


Mobilises body systems during
emergency situations
Flight or fight


Voluntary (somatic motor)
Conducts impulses from CNS to
skeletal mm
Parasympathetic division


Conserves energy
Promotes non-emergency functions
Anatomical and Physiological Differences between the Sympathetic and Parasympathetic Systems
Reference: Marieb & Hoehn (2004)
Characteristic
Origin
Location of ganglia
Parasympathetic
Craniosacral outflow: brain
stem nuclei of cranial nerves III,
VII, IX and X; spinal cord
segments S2 – S4
Ganglia in (intramural) or close
to visceral organ served
Relative length of pre and
postganglionic fibres
Rami communicantes
Long preganglionic; short
postganglionic
None
Degree of branching of
preganglionic fibres
Functional role
Minimal
Neurotransmitters
All fibres release ACh
(cholinergic fibres)
Maintenance of functions;
conserves and stores energy
Sympathetic
Thoracolumbar outflow: lateral
horn of grey matter of spinal
cord segments T1-L2
Ganglia within a few cm of CNS:
alongside vertebral column
(chain or paravertebral ganglia)
and anterior to vertebral
column (collateral or
prevertebral ganglia)
Short preganglionic; long
postganglionic
Grey and white rami
communicantes. White rami
contain myelinated
preganglionic fibres; grey
contain unmyelinated
postganglionic fibres
Extensive
Prepares body to cope with
emergencies and intense
muscular activity
All preganglionic fibres release
Ach; most postganglionic fibres
release norepinephrine
(adrenergic fibres);
postganglionic fibres serving
sweat glands and some blood
vessels of skeletal mm release
Ach; neurotransmitter activity
augmented by release of
adrenal medullary hormones
(norepinephrine and
epinephrine).
2. Describe autonomic tone
Autonomic tone describes the state of the body that the sympathetic and parasympathetic systems
keep. There is sympathetic tone and parasympathetic tone.
The sympathetic nervous system controls most of the vascular system. The sympathetic fibres keep
the blood vessels in a continual state of partial constriction called sympathetic tone or vasomotor
tone. When faster blood delivery is needed, these sympathetic fibres deliver rapid impulses causing
blood vessels to constrict and BP to rise. BP can also be decreased to allow vasodilatation when
required. α blocker drugs that interfere with these vasomotor fibres are used to treat hypertension.
The parasympathetic nervous system dominates the heart and the smooth mm of the digestive and
urinary tract organs. This is referred to as parasympathetic tone.
The parasympathetic tone ensures that the heart beats at a low, normal rate and dictates the
normal activity levels of the digestive and urinary organs. Drugs that block parasympathetic nerve
fibres increase HR and causes faecal and urinary retention.
Except for the adrenal gland, most glands and sweat glands of the skin are also under
parasympathetic control.
3. Describe autonomic neurotransmitter control of the heart, gut and
bladder, including thermoregulation and food intake.
Neurotransmitter – along with electrical signals, are the language of the nervous system. Allows
communication between neurons.
In the ANS there are 2 types of neurotransmitters: Acetylcholine (ACh) and Norepinephrine (NE)
ACh is released by: 1) all ANS preganglionic axons and 2) all parasympathetic postganglionic axons
Fibres that release ACh are called cholinergic fibres.
NE: Most sympathetic postganglionic axons release NE and are called adrenergic fibres. Exceptions
are sympathetic postganglionic fibres innervating sweat glands, some blood vessels in skeletal mm
and external genitalia. These fibres secrete ACh.
Cholinergic: 2 types of receptors that bind ACh.

Nicotinic receptors – always stimulatory

Muscurinic receptors – can be either stimulatory or inhibitory
Adrenergic: 2 major classes α and β receptors

α (2 subclasses) – mostly stimulatory

β (3 subclasses) – mostly inhibitory. Exception is heart mm where it stimulates the heart into
more vigorous activity.
Cholinergic and Adrenergic Receptors
Reference: Marieb & Hoehn (2004) p. 543
Neurotransmitter Receptor Type Major Locations
Acetylcholine
Effect of Binding
Cholinergic
Nicotinic
All ganglionic neurons; adrenal
medullary cells (also
neuromuscular junctions of
skeletal mm)
Excitation
Muscurinic
All parasympathetic target
organs
Excitation in most cases;
inhibition of cardiac mm
Selected sympathetic targets:
Norepinephrine
(and epinephrine
released by
adrenal medulla)

eccrine sweat glands

blood vessels in skeletal
mm
Activation
Inhibition (causes
vasodilation
Adrenergic
β₁
Heart and coronary blood
vessels predominantly, but also
kidneys, liver, and adipose
tissue
Increases heart rate and
strength; dilates coronary
arterioles; stimulates rennin
release by kidneys
β₂
Lungs and most other
sympathetic target organs;
abundant on blood vessels
serving the heart
Stimulates secretion of
insulin by pancreas; other
effects mostly inhibitory:
dilation of blood vessels and
bronchioles; relaxes smooth
muscle walls of digestive
and urinary visceral organs;
relaxes pregnant uterus.
β₃
Adipose tissue
Stimulates lipolysis by fat
cells
α₁
Most importantly blood vessels
serving the skin, mucosae,
abdominal viscera, kidneys and
salivary glands; but virtually all
sympathetic target organs
Constricts blood vessels and
visceral organ sphincters;
dilates pupils of the eyes
except heart
α₂
Membrane of adrenergic axon
terminals; blood platelets
Mediates inhibition of NE
release from adrenergic
terminals; promotes blood
clotting
Thermoregulation
Under control of sympathetic NS
Heat
blood
reflexive dilation of blood vessels
activation of sweat glands to cool the body
skin becomes flushed with warm
Cold
vital organs
reflexive constriction of blood vessels
blood restricted to deeper, more
4. Describe cholinergic and noradrenergic recept or transmission and
second messenger systems
See Q.3 above.
Second Messenger Systems
Adrenergic receptors are associated with specific second messenger systems. They are coupled with
various substances that help to produce an effect.
Second
messengers
and effectors
α₁
α₂
β₁
β₂
β₃
Phospholipase C
activation
↓cAMP
↑cAMP
↑cAMP
↑cAMP
Increased
cardiac rate
and force
Bronchodilatation, lipolysis
vasodilation,
relaxation of
visceral smooth
mm, hepatic
glycogenolysis
↑inositol
triphosphate
↑diacylglycerol
↓Calcium
channels
↑Potassium
channels
↑Ca²⁺
Effects
Vasoconstriction,
relaxation of GI
smooth mm,
salivary
secretion,
hepatic
Inhibition of
transmitter
release
(including
noradrenalin
and
acetylcholine
glycogenolysis
release from
autonomic
nerves),
platelet
aggregation,
contraction of
vascular
smooth mm,
inhibition of
insulin
release
and mm tremor
5. Describe ganglia and co-transmitters
Ganglia

Clusters of neuronal cell bodies

Ganglia associated with afferent nerve fibres contain cell bodies of sensory neurons (dorsal
root ganglia)

Ganglia associated with efferent nerve fibres mostly contain cell bodies of autonomic motor
neurons.
Co-transmitters

There are other transmitters apart from ACh and NE (NAd). This means that autonomic
transmission is not completely blocked by ACh and NE antagonists.

The main co-transmitters are: NO (nitric oxide), VIP (vasoactive intestinal peptide,
parasympathetic), ATP and neuropeptide Y (NPY, sympathetic).

The presence of these co-transmitters means that the autonomic nervous system cannot be
completely blocked; there may still be autonomic effects if an autonomic antagonist drug is
administered.