Neuromuscular Blockers

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Neuromuscular Blockers

• Competitive Antagonists of the Nicotinic Receptor
• e.g. curare (d-tubocurarine), vecuronium,
  pancuronium, atracurium, etc
• Depolarizing Blockers
• e.g. succinylcholine, decamethonium

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Decamethonium
Depolarizing Blockers
Succinylcholine
Vecuronium
Competitive Blockers
D-tubocurarine
pancuronium
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Neuromuscular blockers differ from each other in

• Mechanism of action
• Duration of action
• Speed of onset and offset of action
• Selectivity of action and safety margin
• Adverse effects

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Classification of Blockers
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Site of Action of d-Tubocurarine
Nerve AP
Muscle AP
Left Leg Muscle Stimulation
Right Leg Nerve Stimulation
Right Leg Muscle Stimulation
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Non-depolarizing Block
G gallamine TC tubocurarine NEO neostigmine
S succinylcholine.
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Depolarizing Block
C10 decamethonium TC tubocurarine NEO neostigmi
ne S succinylcholine
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Comparison of Competitive and Depolarizing
Blocking Agents
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Dual Block by Depolarizing Agents
NEO reversed the blockade by C10.
C10 decamethonium NEO neostigmine TC
tubocurarine
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Changing Nature of Neuromuscular Blockade
Depolarizing Blocker
Competitive Blocker
Competitive Blockade
Noncompetitive Blockade
(desensitization) (electrogenic Na pump)
(direct channel block)
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Sequence of Paralysis
Fingers, orbit (small muscles)
limbs
neck
Trunk
Intercostals
Diaphragm
Recovery in Reverse
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Other Effects of Neuromuscular Blockers

• Action at Autonomic Ganglia
• e.g. d-tubocurarine blocks,
• succinylcholine may stimulate
• newer agents have less ganglionic effects
• Histamine Release
• e.g. d-tubocurarine
• bronchospasm, bronchial and salivary secretions

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Adverse Effects/Toxicity

• Hypotension
• Decreased tone and motility in GI tract
• Depolarizing agents can cause increased K efflux
  in patients with burns, trauma, or denervation
  and lead to hyperkalemia
• Prolonged apnea (many reasons, check for
  pseudochlinesterase genetic polymorphism)
• Malignant hyperthermia (succinylcholine
  halothane especially)
• Sinus bradycardia/junctional rhythm (with
  succinylcholine)

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Change in Systolic BP with d-Tubocurarine as a
Function of Dose and Depth of Anesthesia
Increasing Dose of d-tubocurarine
Increasing Depth ( Halothane)
0.25
6 mg/m2
12 mg/m2
0.5
0.75
18 mg/m2
Systolic BP
Systolic BP
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Influence of Type of Anesthetic on Enhancement
of Neuromuscular Blockade By d-Tubocurarine
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Hemodynamic Effects of d-Tubocurarine and
Pancuronium
CO
HR
SVR
MAP
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Drug Interactions

• Cholinesterase Inhibitors (antagonize competitive
  and enhance depolarizing)
• Inhalational Anesthetics (synergistic)
• Aminoglycoside Antibiotics (synergistic)
• Calcium Channel Blockers (synergistic)

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Therapeutic Uses

• Adjuvant in surgical anesthesia
• Orthopedic procedures for alignment of fractures
• To facilitate intubations use one with a short
  duration of action
• In electroshock treatment of psychiatric disorders