Neuromuscular Blocking Agents block neuromuscular transmission at the neuromuscular junction. Classification of Neuro-muscular blocker : 1. Non-depolarizing blocking agents: 2. Depolarizing blocking agents:

1. Neuro-muscular
Blocking Agents
Presented By :
Mr. Sanket Rajiv Shinde
M. Pharmacy (QAT)
Savitribai Phule Pune University

2. Contents
• Introduction
• Autonomic Nervous System
• Para-sympathomimetics and
Parasympatholytics,
• Sympathomimetics and Sympatholytics.
• Neuromuscular blocking agents
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3. 3

4. 4

5. Enteric Nervous System
• GI motility
• Exocrine and Endocrine Secretion (GIT pancrease)
• Brain of gut.
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6. Neurohumoral Transmission
Methods:
• Hormone
• Local mediators like histamine, prostaglandin
• Neurohumoral Transmission
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7. • Impulse Conduction:
• Sudden entry of Na+ (conductance)
• Depolarization
• Refractory period
• Transmission Release:
• Transmitter store in prejunctional nerve
• Nerve impulse promotes fusion of vesicular and axonal
membrane through Ca+ entry.
• Noradrenaline, dopamine
Steps in Neurohumoral Transmission
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8. • Transmitter action on postjunctional membrane:
• EPSP : increase permeability of cations (ca+ and Na+
influx) , Efflux of K+ (depolarization), excitation
• IPSP: increase permeability of anions, cl- moves,
hyperpolarize, Inhibition
• Postjunctional Activity:
• Contraction of muscle, secretion of glands
• Terminate of transmitter action:
• Locally Degrade (Ach)
• Taken by presynaptic neuron (NA)
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9. • Neuromuscular-blocking drugs block neuromuscular transmission at
the neuromuscular junction.
• Causing paralysis of the affected skeletal muscles.
• This is accomplished either by acting pre-synaptically via the
inhibition of acetylcholine (ACh) synthesis or release, or by acting
post-synaptically at the acetylcholine receptors of the motor nerve
end-plate.
• While some drugs act presynaptically (such as botulinum toxin and
tetanus toxin), those of current clinical importance work
postsynaptically.
Neuro-muscular blocking agents
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11. Site of Release: Ach. and NA
• NM receptor: Location & Function
• Neuromuscular junction: depolarization of muscle end plate –
contraction of skeletal muscle
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12. • Non-depolarizing blocking agents:
Example - tubocurarine, pancuronium, vecuronium and
atracurium, Gallamine
• Depolarizing blocking agents:
Example - succinylcholine (suxamethonium), decamethonium
rarely used clinically.
Classification of Neuro-muscular blocker
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13. • They inhibit neuron transmission to muscle by competitively blocking
the binding of ACh to its nicotinic receptors, and block the ionotropic
activity of the ACh receptors.
• Each ACh-receptor has two receptive sites and activation of the
receptor requires binding to both of them. Each receptor site is located
at one of the two α- subunits of the receptor.
Non-depolarizing blocking agents
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14. Mechanism of action
• Quaternary muscle relaxants bind to the nicotinic acetylcholine
receptor and inhibit or interfere with the binding and effect of ACh to
the receptor.
• They are reversible competitive antagonists combine with the nicotinic
ACh receptor at the end plate and thereby competitively block the
binding of ACh.
BlockerBlocker
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15. • A decrease in binding of acetylcholine leads to a decrease in its effect
and neuron transmission to the muscle is less likely to occur.
• Non-depolarising blocking agents also block facilitatory presynaptic
autoreceptors, and thus inhibit the release of ACh during repetitive
stimulation of the motor nerve resulting in the phenomenon of tetanic
fade.
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16. • Action: Tubocurarine occupies muscular cholinergic receptor
site thus preventing Ach from reacting with receptor; no
activation of muscle cells, results in muscle paralysis.
• IV route: Onset 6 min. Duration 25-90 min
• Metabolized in the tissues but excreted unchaged in the urine
• Indication: General anesthesia, Skeletal muscle relaxant
Tubocurarine
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17. • Long Acting : Pancuronium
• Intermediate acting :
• Atracurium
• Vecuronium
• Rocuronium
• Cisatracurium
• Short acting : Mivacurium
Postsynaptic neuromuscular blockers
Competitive (non depolarizing blockers)
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18. Drug
Clinical
Use
Onset of
Time
Duration
of Action
Side Effect
Tubocurarine Rarely 300 Sec.
60-120
Min.
Hypotension(Ganglionic
block),
Bronchoconstriction
Mivacurium Rarely 90 Sec.
12-18
Min.
Transient hypotension
Atracurium Widely 90 Sec. 30 Min or less
Transient hypotension,
renal failure
Vecuronium Widely 60 Sec.
30-40
Min.
Few, prolong paralysis
Pancuronium Widely 90 Sec. 90 Min Tachycardia
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19. Depolarizing blocking agents
• A depolarizing neuromuscular blocking agent is a form of
neuromuscular blocker depolarizes the motor end plate.
• An example is Succinylcholine.
• Depolarizing blocking agents work by depolarizing the plasma
membrane of the muscle fiber, similar to acetylcholine.
• These agents are more resistant to degradation by acetylcholinesterase,
the enzyme responsible for degrading acetylcholine, and can thus more
persistently depolarize the muscle fibers. This differs from
acetylcholine, which is rapidly degraded and only transiently
depolarizes the muscle.
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20. Drug bind with nicotinic receptor
↓
Opening of Na+ and Ca++
channels
↓
Excitation
↓
Depolarization
↓
Paralysis of muscles results in stop
the induction
⟹
⟹
Phase I
(depolarizing phase),
Phase II
(desensitizing phase)
Mechanism of action
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22. • There are two phases to the depolarizing block.
• During Phase I (depolarizing phase), they cause muscular
fasciculation (muscle twitches) while they are depolarizing the
muscle fibers.
• Eventually, after sufficient depolarization has occurred, Phase
II (desensitizing phase) sets in and the muscle is no longer
responsive to acetylcholine released by the motor neurons, and
full neuromuscular block has been achieved.
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23. Adverse Events
• Respiratory depression, hypotension, bronchospasm,
• GI slowdown, Skin breakdown
• Respiratory paralysis
Drug Interaction
• Cholinergic inhibitors
• Antibiotics
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