Parasympathetic Nervous System

Dr. Roland van Rensburg

 ANS: Overview

Alpha (α)
Noradrenaline
Sympathetic
(NA)
Beta (β)

ANS

Nicotinic (Nic)
Acetylcholine
Parasympathetic
(Ach)
Muscarinic
(Mus)
 ANS: Functions
1. Contraction & relaxation of vascular and
visceral smooth muscle
2. All exocrine & certain endocrine secretions
3. Heartbeat
4. Energy metabolism, esp. liver & skeletal
muscle
ANS: Receptors - Sympathetic
• Parasympathetic system = nicotinic &
muscarinic receptors

• Main transmitter
– Acetylcholine (ACh)
ACh synthesis
 Parasympathetic receptors
• Nicotinic
• Muscarinic
 Muscarinic receptors
• 5 subtypes
– M1 (neural)
– M2 (cardiac)
– M3 (glandular/smooth muscle)
– M4/M5 (CNS)

• G-protein coupled
Muscarinic receptors

M1: Neural M2: Cardiac

Autonomic ganglia
Atria (↓ rate & force
(but mostly
of contraction)
nicotinic)

Intramural ganglia
in stomach (↑
secretions)
 Muscarinic receptors
M3:
Glandular/s M4/5: CNS
mooth
muscle

Exocrine Smooth
Blood vessels
glands muscle

Endothelium, causes
Parietal cells GIT (↑ motility & relaxation = nitic oxide
dilates [co-transmitter]
sphincters) (viscera, skin, brain,
Salivary erectile tissue)
glands
Airways (bronchial
constriction)
Lacrimal
glands
Eye (pupil constriction, ciliary
muscle contraction)

Bladder (detrusor contraction,

sphincter relaxation)
 Muscarinic agonists
• Parasympathomimetics
• Agonists at nAChRs & mAChRs
– More potent at mAChRs
• Classical parasympathetic effects
• Acetylcholine (Nic +++, Musc +++)
• Muscarine (Musc +++, Nic -)
• Pilocarpine
– Glaucoma  M3 receptors
 Miosis & ciliary muscle contraction
 S/E: Myopia, ocular irritation
 Muscarinic antagonists

• Parasympatholytics
– b. Hyoscine
• Non-selective
• 1. Alkaloids • Torn apple
• Tertiary ammonium • Penetrates well
compounds • CNS depressant
– a. Atropine
• Non-selective – Side effects
• Deadly nightshade
• Dry mouth
• Penetrates well
• Urinary retention
• CNS stimulant
• Blurry vision (can use atropine
• Used to treat sinus eye drops for uveitis)
bradycardia (via M2-
antagonism) • Sedation (hyoscine)
• 2. Quaternary ammonium compounds
• Does not cross BBB
• Poorly absorbed
– a. Hyoscine butylbromide
• Antispasmodic/motion sickness
• M3
• Scopolamine
– b. Ipratropium
• Bronchodilator
• M3
• Tiotropium similar – long acting
– c. Cyclopentolate/Tropicamide
• Dilates pupil (mydriasis)
• Relaxes ciliary muscle (cycloplegia)
• Eye drops
• M3

Mydriasis Cycloplegia
Cyclopentolate ++ ++
Tropicamide ++ +
Atropine +++ +++
• d. Oxybutynin
– Others: flavoxate, solifenacin, tolterodine
– Urge incontinence/OAB
– Many S/E due to non-specific
– Darifenacin  M3 specific
• Many other CNS anticholinergics as well
– Biperiden
Parkinsonism
– Benzhexol

• Mamba toxin
– M1 & M4
 Nicotinic receptors
• 3 types
– Muscle
– Ganglionic
– CNS (Brain)

• 5 subunits form pentameric structure

– α, β, γ, δ, ε
– Ligand-gated ion channel
 Nicotinic receptors

Muscle Ganglionic CNS

Autonomic
Skeletal NMJ Widespread
ganglia

Mostly Pre- &

postsynaptic postsynaptic
• No clinical use of Ganglion or CNS-type
agonists/antagonists
• Only exception is:
– Varenicline (Champix®)
– Smoking cessation
– Partial agonist on some CNS receptors, full agonist
on others
 Neuromuscular blockade
• During abdominal/eye/thoracic surgery, muscles
need to be relaxed
• Muscle relaxants relax skeletal muscle
• Act on Muscle-type receptors
• Quaternary ammonium compounds, therefore no
CNS stimulation

• Depolarising
• Non-depolarising
 Depolarising
• Non-competitive agonist
• 2x ACh molecules
• Causes depolarising block by binding to ACh receptor
– Activates receptor  Muscle fibres contract (fasciculation) 
Electrical excitability at endplate lost (loss of repolarisation) 
Cessation of fasciculations  Paralysis
– Diffuses away from receptor  hydrolysed by
pseudocholinesterase (plasma cholinesterase)
– Onset ±30 sec / Duration ±5 min
– Used as muscle relaxant in intubation
– ACh binds shorter (rapidly metabolised by cholinesterase), so no
depolarising block
– Acetylcholinesterase drugs actually increase block
• Side effects
1. Postoperative muscle pains
2. Bradycardia
3. Prolonged paralysis
– Genetic plasma cholinesterase deficiency
– Anticholinesterase drugs
– Neonates
4. ↑ K+ release
– Caution in burns (24 hrs – 6 months), immobility
5. Malignant hyperthermia
– Severe muscle contraction & ↑ temperature
– Mutation of Ca2+ channel
– Treated with dantrolene
 Non-depolarising
• Competitive antagonist (= reversible)
• Causes transmission block by displacing ACh from
postsynaptic receptors (concentration-dependant), but
does not depolarise
– Small  large muscle groups
– Extrinsic eye muscles  small muscles of face, pharynx,
limbs  trunk muscles  respiratory muscles
– Resp. muscles last to go & first to return
– Also blocks presynaptic facilitatory autoreceptors to ↓
release of ACh during repetitive stimulation
• Tetanic fade
• Used to gauge postoperative recovery
 Reversal
• Acetylcholinesterase inhibitors
(anticholinesterase)
– Inhibits enzyme that metabolises ACh
= ↑ ACh concentration
– Excessive salivation, lacrimation, GIT motility
– Neostigmine, pyridostigmine
– Also used in myasthenia gravis
• Initially thought to displace drug from receptor
• Now thought to diffuse deeper into synaptic cleft
(than drug) to reach more receptors
– So that effective [ACh] > [drug]
• But then ↑↑ cholinergic/parasympathetic
effects from widespread ACh increase
– Counter effects with anticholinergic to muscarinic
receptors
• Glycopyrrolate
– Quaternary amine
– Does not cross BBB for CNS effects
• Atropine
– Tertiary amine
– Crosses BBB for CNS effects
 ACh release inhibition
• Botulinum toxin
– Botox®
– Clostridium botulinum
– Botulism
– 740 g
• β-bungarotoxin
– Cobra venom

• Causes progressive motor paralysis &

parasympatholytic effects
– Dry mouth, blurry vision, dysphagia
– Respiratory paralysis
 Organophosphate poisoning
• Insecticide
• Frequent mode of attempted suicide
• Accidental overdose
– Stored in empty drink bottles
• Acetylcholinesterase inhibitor
– Similar to neostigmine/pyridostigmine
Clinical features
• SLUDGE/BBB:
– Salivation
– Lacrimation
– Urination
– Defecation
– Gastric Emesis (Vomiting)

– Bronchorrhoea
– Bronchospasm
– Bradycardia
Suxamethonium!
 Management
• Atropine
– Antagonises widespread nicotinic & muscarinic
receptor activation
– Most sensitive sign of improvement  cessation
of bronchial secretions & spasm