Post-synaptic

Inhibit binding, Inactivate channels

Non-depolarising
blockers
Competitive
antagonist at
nicotinic (N)
receptors
Overcome by
increasing ACh
(E.g. Introducing
antichoninesterase)
No initial stimulant
action
Antagonist
competes with ACh
on binding sites,
reducing probability
of reaching
threshold potential

Depolarising blockers
Stimulate N receptors
(Agonists)
Potentiated by increasing
ACh.
Initial muscle fasciculation
Agonists act at muscle end
plate, preventing cycles of
depolarization ad
repolarization, thus stopping
sustained muscle
contraction.
Na+ channel inactivated,
receptors become
unresponsive to ACh
Suxamethonium (3-7min)
Hydrolised rapidly by
plasma cholinesterase (NOT
AChE)
This enz may not be present
in some people, causing
paralysis
Problem: No drug reverses
depolarizing blockers

Tubocurarine (60120min)
Ganglion blockade,
histamine release
Vecuronium (3040min)
Atracurium
(<30min)
Mivacurium (1520min)
Effects
- Paralysis
- Unable to breathe

Uses
- Muscle relaxation
during anesthesia
- Facilitate tracheal
intubation
- Facilitate
mechanical
ventilation

Pre-synaptic
Inhibit ACh
synthesis/relea
se
Botox
Cleaves SNAP-25,
inhibiting release
of Ach (No
docking occurs
Reduce amount
of ACh released,
harder to reach
threshold
potential
Effect:
- Treat
muscle
spasms
- Prevent
frowning
Long lasting &
irreversible

Within
Synaptic Cleft
Anticholinesterase IMPORTANT
Prevents AChE from cleaving ACh.
Can be reversible and reversible

Affects NMJ, CNS (if BBB is crossed)

and autonomic cholinergic synapses.
Observed as an enhancement of ACh
activity
Symptoms
- Parasympathetic overactivity
- Sweating, salivation,
bradycardia
- Skeletal muscle fasciculation
and nneuromuscular blockade
- Respiratory failure
Treatment
- Atropine: Blocks muscarinic
actions of ACh (antagonist)
- Pralidoxime: Antidoe for
pesticides, reactivates
cholinesterase
Enzyme will age, thus reactivation
must be quick
+ Artificial ventilation due to
respiratory failure
Drugs Reversible: Useful in
overcoming effects of nondepolarising blocking drugs
(tubocurarine Increases ACh
and thus can overcome
- Physostigmine
- Neostigmine
- Edrophonium (shorter acting
Irreversible drugs
- Ecothiopate for glaucoma,
long lasting
- Agricultural insecticides
(malathion)
- Nerve gases (sarin)

Myasthenia gravis

Muscle weakness
Fewer AP produced due to
lower number of N receptors
Antibodies formed on N
receptors, which decrease the
availability of N receptors,
making failure more likely to
occur.
Autoimmune: Body itself
creates antibodies, prevents
ACh from finding receptor and
initiating contraction
Treatment
- Anticholinesterase, to
increase ACh concentration to
increase likelihood of
receptor/NT interaction
- Atropine to block unwanted
M effects?
- Corticosteroids or
immunosuppressants:
Suppress immune response
to reduce amount of
antibodies produced
Other treatments
- ACh: Not possible as it is
hard for ACh tor each
synaptic cleft
-