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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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D-tubocurarine pancuronium
Vecuronium
Decamethonium
SuccinylcholineDepolarizing
Blockers
CompetitiveBlockers
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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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Agent Pharmacological
Properties
Onset time (min)
Duration
(min)
Elimination
Succinylcholine Ultrashort acting;
Depolarizing1-1.5 6-8
Plasma cholinesterase
D-tubocurarine Long duration;
Competitive4-6 80-120
Renal and liver
Atracurium Intermediate duration;
Competitive2-4 30-40
Plasma cholinesterase
Mivacurium Short duration;
Competitive2-4 12-18
Plasma cholinesterase
Pancuronium Long duration;
Competitive4-6 4-6
Renal and liver
Rocuronium Intermediate duration;
competitive1-2 1-2
Renal and liver
Classification of Blockers
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Muscle AP
Nerve AP
Left Leg Muscle Stimulation
Right Leg Nerve Stimulation
Right Leg Muscle Stimulation
Site of Action of d-Tubocurarine
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G: gallamine; TC: tubocurarine; NEO: neostigmine; S: succinylcholine.
Non-depolarizing Block
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Depolarizing Block
C10: decamethoniumTC: tubocurarineNEO: neostigmineS: succinylcholine
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Competitive Depolarizing
Effect of previous d-tubocurarine
Additive Antagonistic
Effect of previous decamethonium
None/antagonistic May be additive
Efect of cholinesterase inhibitors
Reverse No antagonism
Effect on motor end plate
Elevated threshold to Ach; no depolarization
Partial, persisting depolarization
Initial excitatory effect None Transient fasciculations
Effect of KCl or tetatnus on block
Transient reversal
No antagonism
Comparison of Competitive and Depolarizing Blocking Agents
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Dual Block by Depolarizing Agents
C10: decamethonium; NEO: neostigmine; TC: tubocurarine
NEO reversedthe blockadeby C10.
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Depolarizing Blocker
Competitive Blockade
Competitive Blocker
Noncompetitive Blockade
(desensitization)(electrogenic Na pump)
(direct channel block)
Changing Nature of Neuromuscular Blockade
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Sequence of Paralysis
Fingers, orbit (small muscles)
limbs Trunk neck
IntercostalsDiaphragm
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Other Effects of Neuromuscular Blockers
• Action at Autonomic Ganglia e.g. d-tubocurarine blocks, succinylcholine may stimulatenewer agents have less ganglionic effects
• Histamine Release e.g. d-tubocurarinebronchospasm, 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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Systolic BP Systolic BP
% Change in Systolic BP with d-Tubocurarine as a Function of Dose and Depth of Anesthesia
Increasing Doseof d-tubocurarine
Increasing Depth(% Halothane)
0.25%
0.5%
0.75%
6 mg/m2
12 mg/m2
18 mg/m2
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Influence of Type of Anesthetic on Enhancement of Neuromuscular Blockade By d-Tubocurarine
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HR CO
SVR MAP
Hemodynamic Effects of d-Tubocurarine and Pancuronium
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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
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