The document discusses the neuromuscular junction, which allows motor neurons to transmit signals to muscle fibers and cause contraction. It consists of a presynaptic motor neuron, synaptic cleft, and postsynaptic muscle fiber. Acetylcholine is released from the motor neuron, binds to nicotinic receptors on the muscle fiber, and triggers an action potential for contraction. Neuromuscular blocking agents used in surgery work by competitively blocking acetylcholine receptors. They can be depolarizing like succinylcholine or non-depolarizing like tubocurarine. Centrally-acting muscle relaxants reduce muscle tone by affecting the central nervous system. Disorders of the neuromuscular junction include myast

2. INTRODUCTION
It is also called as myoneural junction.
It is a chemical synapse formed by the contact
between a motor neuron and a muscle fiber.
It is the neuromuscular junction that a motor
neuron is able to transmit a signal to the
muscle fibre, causing muscle contraction.

3. NEUROMUSCULAR JUNCTION CONSISTS OF
A. Terminal button
B. Presynaptic membrane
C. Vesicles
D. Synaptic cleft
E. Neurotransmitters
F. Post synaptic membrane
G. Receptors

4. NEUROMUSCULAR TRANSMISSION
In neuromuscular system both Central N.S and
Peripheral N.S are linked and work together with
muscles.
This mechanism consists of 3 parts,
 Pre-synaptic events
 Synaptic events
 Post-synaptic events

5. NEUROMUSCULAR TRANSMISSION
 Pre-synaptic events:
Action potential arrives at the axon terminal and
depolarize the membrane of terminal button.
This activate and open the calcium gated channels.
The calcium influx leads to the release of
acetylcholine into the synaptic cleft.

6. NEUROMUSCULAR TRANSMISSION
Synaptic cleft events:
 The binding of neurotransmitter to the receptors present
on the post-synaptic membrane
 There are acetylcholine esterase’s (AchE) present in the
synaptic cleft to neutralise the released neurotransmitters
(Ach).

7. NEUROMUSCULAR TRANSMISSION
Post-synaptic events:
 The released acetylcholine bind to the specific receptors.
 These receptors consists of 5 subunits, the Ach binds to
the α-subunits.
 The action potential is generated in the post synaptic
muscle fibre by sodium influx.

8. REMOVAL OF ACETYLCHOLINE
The acetylcholine is
degraded by
Acetylcholinesterase's
in synaptic cleft.
Remaining are
diffused out of the
cleft and no longer
available for use.

9. MINIATURE END PLATE POTENTIAL
At rest, small quantity
of ach is released from
the nerve terminal.
This causes the
Production of end-plate
Potential of about 0.5mV
Which is Miniature End-
Plate Potential

10. DRUGS AFFECTING NEUROMUSCULAR JUNCTION
Skeletal muscle relaxants are drugs that act peripherally at
neuromuscular junction/muscle fibre itself or centrally in
the cerebrospinal axis to reduce muscle tone and/or
cause paralysis.
The neuromuscular blocking agents are used primarily in
conjunction with general anaesthetics to provide muscle
relaxation for surgery, while centrally acting muscle
relaxants are used mainly for painful muscle spasms and
spastic neurological conditions.

12. NEUROMUSCULAR BLOCKING AGENTS
Depolarizing blockers: mechanism of action
o These closely resemble the acetylcholine and readily
bind to ach receptors.
o These are not metabolised by ach esterase, resulting into
the prolonged depolarization of the muscle end plate.
o Causes muscle relaxation.

13. PHASES OF DEPOLARISING BLOCKERS
Phase 1 block :
 Rapid onset.
 The pre-junctional sodium channels cannot re-open until the end
plate repolarises.
 As long as the blocker binds to the Ach receptor, end-plate cannot
repolarise.
Phase 2 block :
 Onset is slow.
 This block is the result of desensitization of the receptor to
acetylcholine.

14. SUCCINYLCHOLINE:
 Quaternary ammonium compound.
 Also known as Diacetyl choline or Suxamethonium.
 2 acetylcholine molecules are joined to form
succinylcholine.
 This uses the same phase 1 and phase 2 blocking
mechanism.
 It induces rapid, complete and predictable paralysis
with spontaneous recovery within 5 mins.
 Common muscle relaxant for tracheal tube.

15. MECHANISM OF ACTION

16. MECHANISM OF ACTION
It stimulates Nm nicotinic receptors and depolarises the skeletal
muscle membrane .
It causes flaccid paralysis because of the continuous presence of
the drug.
This is the phase 1 block.
In high dose it produce dual block.
Initially depolarization block followed by non-depolarising
block.
Succinylcholine is destroyed very slowly by
pseudocholinesterase

17. NON-DEPOLARISING BLOCKERS
They have more affinity towards the
nicotinic(Nm) cholinergic receptors at
muscle end plate.
They don’t have intrinsic activity.

18. NON-DEPOLARISING BLOCKERS
 d-Tubocurarine:
Curare was used by the South Amarican
Indians for hunting Wild animals, because
curare paralysed the animals.
This alkaloid is obtained from the plant
Chondrodendron tomentosum and plants of the
Strychnos species.

19. MECHANISM OF ACTION

20. MECHANISM OF ACTION
Non-depolarising blockers (d-Tc) bind to Nm
nicotinic receptors on the motor end plate and
block the actions of acetylcholine by competitive
blockade.
These compounds slowly dissociate from the
receptors and transmission is gradually restored.
The action of d-Tc is reversible.

21. PHARMACOLOGICAL ACTIONS
Skeletal muscle: On parenteral administration, tubocurarine initially
causes muscular weakness followed by flaccid paralysis.
the occurance of paralysis,
Eyes, Fingers
Limbs, Neck, Trunk
Intercostal Muscle
Diaphragm
Respiration stops
Consciousness is not affected throughout.
The recovery occurs in the reverse order.

22. Autonomic ganglia: In high doses tubocurarine
can block autonomic ganglia and adrenal
medulla resulting in hypotension.
Histamine release: Tubocurarine can cause
histamine release from the mast cells leading
to bronchospasm, increased tracheobronchial
and gastric secretions. Histamine release also
contributes to hypotension.

23. PHARMACOKINETICS
Tubocurarine and other NMBs are quaternary
ammonium compounds, hence not
absorbed orally, and do not cross BBB.
They are given either IM or IV.
They get excreted very quickly.

24. ADVERSE REACTIONS
Respiratory paralysis and prolonged apnoea
Hypotension
Flushing and bronchospasm

25. DIFFERENCE

26. DIRCTLY ACTING ON SKELETAL MUSCLE
Directly act on skeletal muscles.
Inhibits the depolarisation induced calcium
release from sarcoplasmic reticulum.
Used in multiple sclerosis, cerebral palsy, spinal
injuries, etc.
Side effects are headache, dizziness, fatigue,
diarrhoea, rarely hepatotoxicity.

27. DANTROLENE
It is the phenytoin analogue that act directly on skeletal muscle.
Mechanism of action:
Since other subtypes of ryanodine receptor is involved in cardiac and
smooth muscles, they are not affected much.

28. CENTRALLY ACTING MUSCLE RELAXANTS
These are drugs which reduce skeletal muscle tone by a
selective action in the cerebrospinal axis.
They usually don’t alter the consciousness.
They selectively depress spinal and supraspinal
polysynaptic reflexes.
They do have sedative property.

29. CLASSIFICATION
Mephenesin congeners: Mephenesin,
Chlorzoxasone, Chlormezanone.
Benzodiazepines: Diazepam and others
GABA mimetic: Baclofen, thiocolchicoside
Central α2 agonist: Tizanidine

30. Baclofen:
It is the analogue of inhibitory transmitter GABA.
It acts on both GABAA and GABAB receptors
Primarily it act on spinal cord, depress synaptic and
monosynaptic reflexes.
Produce muscle weakness.
It is well absorbed orally, excreted within 3-4 hours

31. USES OF CENTRALLY ACTING MUSCLE
RELAXANTS
Acute muscle spasms.
Anxiety and tension.
Spastic neurological diseases.
Electroconvulsive therapy.
Orthopedic manipulations.

32. COMPARATIVE DIFFERNCE

33. DISORDERS RELATED TO THE
NEUROMUSCULAR JUNCTION ARE
• Myasthenia gravis
• Lambort-Eaton syndrome

34. THANK YOU