The Autonomic Nervous System (Ans) : 2022-12-19 BSC Nursing Science Ii - by Patrick R Matowa 1

The Autonomic Nervous
System (ANS)
BSc Nursing Science II -----------by Patrick R

2022-12-19 1
Matowa
Learning Objectives
• Demonstrate an understanding of the
peripheral nervous system, its functions and
relationship to drugs.
• Describe the divisions of the autonomic
nervous system and how they differ from each
other.
• Describe and explain how adrenergic and
cholinergic drugs affect body systems and
where they work in the body.
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Autonomic nervous system
The ANS is a subdivision of the peripheral nervous

system (PNS) that regulates body activities that are
generally not under conscious control
Visceral motor innervates non-skeletal (non-somatic)
muscles
 Composed of a special group of neurons serving:
◦ Cardiac muscle (the heart)
◦ Smooth muscle (walls of viscera and blood vessels)
◦ Internal organs
◦ Skin

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• Axon of 1st (preganglionic) neuron leaves CNS
to synapse with the 2nd (ganglionic) neuron
• Axon of 2nd (ganglionic) neuron extends to the
organ it serves
Diagram contrasts somatic (lower) and autonomic:
autonomic
this dorsal
root ganglion
is sensory
somatic

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Note: the autonomic ganglion is motor
Divisions of the ANS
• Parasympathetic division
• Sympathetic division

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Divisions of the autonomic nervous system
• Parasympathetic division
• Sympathetic division
Serve most of the same organs but cause

opposing or antagonistic effects
Parasysmpathetic: routine maintenance

“rest &digest”
Sympathetic: mobilization & increased metabolism
“fight, flight or fright” or “fight, flight or freeze”
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Origins
Parasympathetic: Sympathetic:
craniosacral thoracolumbar

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Parasympathetic Effects
• Release of Acetylcholine
• Relaxing effects:
– Decreases heart rate
– Dilates visceral blood vessels
– Increases digestive activity
• Bronchoconstriction
• Tears, nasal mucus, salivation
• GI motility increases
• Relaxation of sphincters
• Contraction of:
– Detrusor muscle
– Ciliary muscle
• Miosis
BSc Nursing Science II -----------by

2022-12-19 8
Patrick R Matowa
Sympathetic nervous system
“fight, flight or fright”
• Lead to every part of the body (unlike parasymp.)
– when nervous, you sweat;
– when afraid, hair stands on end
– when excited blood pressure rises (vasoconstriction)
– Also causes: dry mouth, pupils to dilate, increased heart &
respiratory rates to increase O2 to skeletal muscles, and liver to
release glucose
• Norepinephrine (noradrenaline) is neurotransmitter
released by most postganglionic fibers (acetylcholine in
preganglionic):
→ “adrenergic”

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Adrenal gland is exception
On top of kidneys
Adrenal medulla
(inside part) is a
major organ of the
sympathetic
nervous system

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Adrenal gland (cont)
• Synapse in gland
• Can cause body-wide
release of
epinephrine/adrenaline
and norepinephrine in
an extreme emergency
(adrenaline “rush” or
surge)

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Sympathetic Effects
• Fight, fright or flight response
• Release of neurotransmitters
– Norepinephrine from postganglionic fibers
– Epinephrine from adrenal medulla
• Mass activation prepares for intense activity
– Heart rate increases, Bronchioles dilate and
– Blood glucose increases
• GI motility decreases
• Contraction of sphincters
• Relaxation of
– Detrusor muscle and Ciliary muscle
• Mydriasis
BSc Nursing Science II -----------by
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Patrick R Matowa
Summary

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CHOLINERGICS AND
ANTICHOLINERGICS
Background (cont)
• Transmission is named for the specific
neurotransmitter involved
• Thus, cholinergic transmission involves the release
of the neurotransmitter Acetylcholine (ACh), and
its activation of the postsynaptic receptor
• The cholinergic system is also activated by
exogenously added nicotine and muscarine
→ nicotinic cholinergic receptors and muscarinic
receptors.
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Muscarinic receptors
• 3 well characterised subtypes:
– M1; brain and gastric parietal cells
– M2; heart
– M3; smooth muscle and glands
• Effects of Ach on the receptors are selectively
blocked by Atropine

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Nicotinic receptors
• Occur in autonomic ganglia and adrenal
medulla
• Effects are selectively blocked by
hexamethonium

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Actions of Acetylcholine
• Muscarinic effects:
– Tear secretion
– Constriction of pupil
– Profuse watery salivation
– Broncho-secretion, bronchoconstriction
– Bradycardia, vasodilation
– Hypotension
– Increase in motility and tone
– Micturition
– Erection
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Parasympathetic Responses

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Cholinomimetics
• Are divided into two groups:
– Directly acting
• nicotinic and
• muscarinic agonists
– Indirectly acting
• anticholinesterases

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Directly acting
• Muscarinic agonists:
– Pilocarpine (as eye drops)
• reduce intraocular pressure in glaucoma patients
– Carbachol & bethanechol

• used to stimulate the bladder in urinary retention
where there is no obstruction to the bladder outlet.

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Indirectly acting
• Anticholinesterases
– Quartenary compounds
• Edrophonium
• Neostigmine
• Pyridostigmine
- do not cross the blood brain barrier (BBB) and
- are poorly absorbed orally

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• Tertiary amines
• Physostigmine
• more lipid soluble
• Passes the BBB and
• well absorbed orally.
- Uses
- in the treatment of myasthenia gravis and
- to reverse the effects of competitive muscle
relaxants used during surgery
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• Indirectly acting agents used to treat AD
– Donepezil
– Galantamine
– Rivastigmine
– Tacrine

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Toxicity of muscarinic agonists
• Resemble signs of extreme muscarinic
stimulation:
– miosis, salivation, sweating, bronchoconstriction,
bronchosecretion, vomiting and diarrhoea
• If the drug is lipid soluble, eg physostigmine,

– convulsions, coma & respiratory arrest may occur.

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Muscarinic antagonists
• Atropine, scopolamine, hyoscine, ipratropium, tiotropium,
dicyclomine, tropicamide, homatropine
– Block the effects of Ach released from postganglionic
parasympathetic nerve terminals
– Atropine dilates the pupil and paralyzes the ciliary muscle
accommodation, blurring vision
• Uses:
– anaesthesia;
• to block vagal slowing of the heart and to inhibit bronchial secretions
– To reduce intestinal spasms
– In Parkinson’s disease and dystonic reactions caused by
antipsychotics - Benztropine
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Uses (cont)
• to prevent motion sickness (hyoscine)
• As a mydriatic,
• to dilate the pupil for ophthalmological exam by
blocking contraction of the circular pupillary
sphincter muscle.
• As a cycloplegic,
• to temporarily paralyse the accommodation reflex
by paralysing the ciliary muscle
• Tx of EPS by antipychotics (Trihexyphenidyl)
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Uses (cont.)
• Urinary incontinence
– Oxybutynin
• Organophosphate poisoning treatment
– Atropine
• Preoperative
– To prevent vagal stimulation and potential bradycardia
– Reduce respiratory secretions
• Treatment of bradycardia
• In bronchospasm
– Asthma
– COPD

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Atropine adverse effects
• Constipation
• Vasodilation (atropine flush)
• Histamine release
Toxic doses of atropine cause excitement, agitation,

hallucination and coma.

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Ganglion blockers
• Hexamethonium
• Trimetaphan
• Mecamylamine
– Used in BP emergencies to lower BP
– Side effects include:
• hypotension, mydriasis, dry mouth, constipation,
urinary retention & impotence

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DRUGS ACTING AT ADRENERGIC
NERVE TERMINALS
• AGONISTS
• ANTAGONISTS

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SYMPATHOMIMETIC DRUGS

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Classification
• Directly acting
- Norepinephrine - salbutamol
- Epinephrine - phenylephrine
- Dopamine - isoproterenol
- dobutamine
• Indirectly acting
(a) Displacement of stored catecholamines (tyramine, ephedrine,
amphetamine [TEA])
(b) Inhibition of reuptake of catecholamines (cocaine, TCAs)
→ both result in activation of adrenoceptors
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Adrenoceptors
• Alpha receptors
– α₁
– α₂
• Beta receptors
– β₁
– β₂

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• Beta-1 agonists
– Dobutamine
– Isoproterenol (β₁ and β₂)
– Xamoterol
– Epinephrine

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• Beta-2 agonists
– Salbutamol
– Formoterol
– Isoproterenol (β₁ and β₂)
– Salmeterol
– Terbutaline
– Epinephrine

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• Alpha-1 agonists
– Methoxamine
– Oxymetazoline
– Phenylephrine
 Alpha-2 agonists
Clonidine
Guanethidine
Tizanidine
Methyldopa
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ADRENOCEPTOR BLOCKING DRUGS

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Alpha blockers
• Reversible
– Phentolamine
– Tolazoline
– Prazocin, labetolol (mixed α and β)
• Duration of action dependent on drug half life
• Irreversible
– Phenoxybenzamine
– Binds covalently to α receptors
• Duration not dependent on half life

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• Non-selective
– Phenoxybenzamine
– Phentolamine
– Tolazoline
– Trazodone
• Selective α₁
– Prazosin
– Doxazosin
– Tamsulosin
– Terazosin
• Selective α₂
– Yohimbine
– Mirtazapine
– Atipamezole

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• Pharmacologic effects
CVS
- Lowering of TPR & BP
- Postural hypotension
- Reflex tachycardia
Other effects
- Miosis
- Decreased adrenergic sweating
- Nasal stuffiness
- Decreased resistance to the flow of urine
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• Prazosin
– Hypertension
– Highly selective for α₁ and low affinity for α₂
– Relax both arterial & venous smooth muscle
– Extremely metabolised in the liver;
– about 50% bioavailability.

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• Uses:
– pheochromocytoma:
• phentolamine, phenoxybenzamine
– Hypertensive emergencies:
• labetolol, phentolamine
– Chronic Hypertension:
• prazosin

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Beta receptor blockers
• Reduce receptor occupancy by catecholamines
and β-agonists
• Non-selective
– Propranolol, carvedilol, labetalol, nadolol, oxprenolol
• β₁ selective (cardioselective)
– Atenolol, metoprolol, esmolol, bisoprolol, betaxolol,
acebutolol, nebivolol
• β₂ selective
– butoxamine
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• Pharmacodynamics
CVS
- Lower BP and hypertension
- Negative inotropic & chronotropic effects
- Block β₂ mediated vasodilation
- Antagonise release of renin
Other:
- Increase in airway resistance
- Decrease in intraocular pressure
- Inhibits lipolysis
- Inhibits glycogenolysis
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• Uses:
– Hypertension:
• with a diuretic or vasodilator
– Ischaemic heart disease
– Cardiac arrhythmias
– Glaucoma
– Migraine headaches
– hyperthyroidism

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Summary

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Overview of Nervous System

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Summary
• CNS consists of the brain and spinal cord
• Efferent nerves relay information from the CNS to
all parts of the body (periphery)
• Afferent nerves relay information from the
periphery to the CNS
• 2 types of efferent nerves
1. Somatic – which innervates the skeletal muscles
2. Autonomic/Visceral – which innervates smooth
muscle, glands and heart
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Summary (cont)
• When a conducted electrical impulse reaches
the nerve terminus, it provokes the release of
chemicals called neurotransmitters
• Neurotransmitters diffuse across the synaptic
cleft and react with a receptor on the
postjunctional membrane
• Receptor activation triggers a series of chemical
events resulting in a biological response; such
as muscle contraction
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Summary (cont)
• Transmission is named for the specific
neurotransmitter involved
• Thus, cholinergic transmission involves the release
of the neurotransmitter Acetylcholine (ACh), and
its activation of the postsynaptic receptor
• The cholinergic system is also activated by
exogenously added nicotine and muscarine
– → nicotinic cholinergic receptors and muscarinic
receptors.

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NEUROMUSCULAR
BLOCKING DRUGS
Introduction
 Skeletal muscle contraction is evoked by a

nicotinic-cholinergic transmission process.
 Muscle relaxation is a requirement for surgery
 Blockade at the endplate (the postsynaptic

structure bearing the nicotinic receptors) is
clinically useful in producing muscle relaxation
BSc Nursing Science II

-----------by Patrick R Matowa 2022-12-19 54
 The neuromuscular junction:
◦ The body contains several different skeletal
muscles & each consists of thousands of muscle
fibres & are innervated by nerve fibres arising from
the spinal cord.
◦ The particular type of synapse, area between the
terminal tip of each nerve fibre and the endplate of
each muscle, is called the neuromuscular junction.
◦ The neuromuscular transmission responsible for
the complex & finely controlled movements depend
on the release from the motor nerve terminals of
the chemical acetylcholine (Ach).

Neuromuscular blocking drugs
 Are quartenary amines structurally related to Ach
 Interfere with the transmission at the
neuromuscular endplate.
 Are not CNS-active drugs
 Are highly polar & inactive when given orally
 Do not cross membranes well & have limited Vd
(80-140ml/kg).
 Most are antagonists
◦ non-depolarising
 One is an agonist at the nicotinic end-plate receptor
◦ depolarising

Non-depolarising neuromuscular
blockers
 Tubocurarine is the prototype
 Mivacurium, atracurium, vecuronium,
pancuronium, gallamine, doxacurium,

rocuronium, pipecuronium
 MOA:
◦ Bind to the nicotinic Ach receptor & prevent the

action of Ach at the skeletal muscle end plate
 → act as surmountable blockers.
◦ Their effect is reversed by cholinesterase inhibitors.

 Pharmacokinetics:
◦ All are given parenterally
◦ Agents that are metabolised (e.g mivacurium, by
plasma cholinesterase) or eliminated in the bile (e.g
vecuronium) usually have shorter durations of
action than those eliminated by the kidney (e.g
pancuronium, tubocurarine)
 Side effects:
◦ hypotension, flushing & tachycardia from histamine
release
◦ Muscle pain
◦ Increase in intra-gastric pressure.

Depolarising neuromuscular blocking
drugs
 Succinylcholine
 M.O.A:
◦ Acts like nicotinic agonists; bind to & activate the
receptor, causing contraction & eventually
paralysation.
◦ The initial depolarisation is often accompanied by
twitching & fasciculations
◦ Continuous depolarisation results in muscle
relaxation & paralysis.
◦ There are 2 phases to the depolarising block

Phases of depolarising block
 Phase 1: depolarising phase
◦ Reacts with nicotinic receptor to open the channel &
cause depolarisation of the endplate
◦ The depolarised membranes remain depolarised &
unresponsive to additional impulses because
succinylcholine is not effectively metabolised at the
cleft.
◦ They cause muscular fasciculations (muscle
twitches) while depolarising the muscle fibres.

Cont.
 Phase 2: desensitising phase
◦ The muscle is no longer responsive to Ach released
by motor neurons as long as succinylcholine is
present
 → full neuromuscular block has been achieved.
◦ Suxamethonium is the only such drug used
clinically

 Pharmacokinetics
◦ Succinylcholine is composed of 2ACh molecules
linked end to end
◦ Metabolised by plasma cholinesterase
(butyrylcholinesterase/pseudocholinesterase) which
determines the amount of drug reaching the end-
plate.
◦ Has rapid onset of action (30 seconds).
◦ Duration of action ≈ a few minutes (5-10mins)
◦ Prolonged blockade in patients with genetic
variants of plasma cholinesterase that metabolises
succinylcholine very slowly.
◦ Not rapidly hydrolysed by acetylcholinesterase

Succinylcholine
 Continuous infusion of succinylcholine will
result in the effect changing from continuous
depolarisation (phase 1) to gradual
repolarisation with resistance to depolarisation
(phase 11)
◦ → a curare-like block.
 In depolarising the musculature,
suxamethonium may trigger a transient release
of large amounts of K⁺ from muscle fibres.
 Side effects
◦ hyperkalemia, cardiac arrhythmias

Reversal of blockade
 The effects of non-depolarising blockers is
reversed by increasing the concentration of
normal transmitter at the receptors.
◦ → by admin of cholinesterase inhibitors
 neostigmine, pyridostigmine
 In contrast, the paralysis produced by
depolarising blockers is increased by
cholinesterase inhibitors during phase 1.
 The block produced by succinylcholine during
phase 11 is usually reversible by cholinesterase
inhibitors.

Toxicity
 Respiratory paralysis
 Autonomic effects and histamine release
◦ Succinylcholine stimulate autonomic ganglia
◦ Succinylcholine stimulates cardiac muscarinic
receptors
◦ Tubocurarine blocks the autonomic ganglia
◦ Tubocurarine cause histamine release
◦ Vecuronium has a moderate blocking effect on
cardiac muscarinic receptors.

 Specific effects of succinylcholine:
◦ Muscle pain & damage, hyperkalaemia (esp in
patients with burns or spinal cord injury, peripheral
nerve dysfunction, muscular dystrophy), increased
intra-gastric pressure → emesis
 Interactions:
◦ Inhaled anaesthetics (isoflurane) potentiate &
prolong neuromuscular blockade.
◦ Aminoglycosides & anti-arrhythmics potentiate &
prolong the relaxant action of neuromuscular
blockers to a lesser degree.


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The Autonomic Nervous

BSc Nursing Science II -----------by Patrick R

The ANS is a subdivision of the peripheral nervous

BSc Nursing Science II -----------by Patrick R

Diagram contrasts somatic (lower) and autonomic:

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

Serve most of the same organs but cause

Parasysmpathetic: routine maintenance

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

– Carbachol & bethanechol

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

• If the drug is lipid soluble, eg physostigmine,

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

Toxic doses of atropine cause excitement, agitation,

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

• Duration of action dependent on drug half life

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

BSc Nursing Science II -----------by Patrick R

 Skeletal muscle contraction is evoked by a

 Muscle relaxation is a requirement for surgery

 Blockade at the endplate (the postsynaptic

BSc Nursing Science II

BSc Nursing Science II

BSc Nursing Science II

pancuronium, gallamine, doxacurium,

◦ Bind to the nicotinic Ach receptor & prevent the

BSc Nursing Science II

BSc Nursing Science II

BSc Nursing Science II

BSc Nursing Science II

BSc Nursing Science II

BSc Nursing Science II

◦ hyperkalemia, cardiac arrhythmias

BSc Nursing Science II

BSc Nursing Science II

BSc Nursing Science II