Neuromuscular
Blocking Agents
Pawitra Pulbutr
M.Sc. In Pharm (Pharmacology)
วัตถุประสงค์เชิงพฤติกรรม
• นิ สติ มีความรูค้ วามเข้าใจถึงเภสัชวิทยา กลไกการออกฤทธิ์ เภสัช
จลนศาสตร์ การใช้ประโยชน์ทางคลินิก อาการไม่พงึ ประสงค์ และ
ปฏิกริ ยิ าระหว่างยา ของยาหย่อนกล้ามเนื้ อชนิ ด Nondepolarizing blocking agents และ
Depolarizing blocking agents
• นิ สติ มีความเข้าใจถึงความแตกต่างของการตอบสนองของกล้ามเนื้ อต่อ
ยาหย่อนกล้ามเนื้ อชนิ ด Non-depolarizing
blocking agents และ Depolarizing
blocking agents
Muscle relaxing drugs
• Neuromuscular blocking agents
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Neuromuscular blocker
Acting on NMJ
Use in surgery
Focus here !
• Centrally acting muscle relaxants
– Spasmolytic agent
– Diazepam, Baclofen
– CNS drug
• Dantrolene
– Direct acting at skeletal muscle
Neuromuscular junction
(NMJ)
Motor
nerve
NMJ
• Junction b/w motor
nerve terminal
(somatic nerve) and
skeletal muscle
• NTs = Acetylcholine
(ACh)
• Motor end plate
contain Nicotinic
Receptor & AChE
How to block end plate
function ?
• Antagonist drugs
– Interfere ACh binding to nicotinic RC
at end plate
– “Non-depolarizing blocking agents”
– Prototype = Tubocurarine
• Depolarizing block
– Excess depolarizing agonist
– “Depolarizing blocking agents”
– Succinylcholine
Mechanism of action
• Non-depolarizing blocking agents
– All are this type (except succinylcholine)
– Prototype = “Tubocurarine”
– Competitive binding with ACh to
Nicotinic ACh RC at motor end plate
– “Competitive antagonist”
– May block in ion channel of RC
(Pore blocking)
– Also block at prejunctional receptor …
Interfere ACh mobilization in nerve
Characteristic of Nondepolarizing blockers
No muscle fasciculation
Tetanic fading
Post tetanic potentiation
Competitive binding with ACh
Antagonism with “AChE inhibitor”
… increased ACh
Depolarizing blocking agents
Decamethonium & Suxamethonium
(succinylcholine)
Succinylcholine … Only one left
Fast onset & short duration
Phase I block
depolarizing block
Phase II block
desensitization
non-depolarizing block
Phase I block
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Depolarizing block
Bind to Nicotinic RC … depolarization
Prolong ion conductance & depolarization
No repolarization
No excitation-contraction coupling
No muscle contraction
Flaccid paralysis
Potentiation by AChE inhibitor
Characteristic of Phase I
Block
Muscle fasciculation before relaxation
No tetanic fading … Just lower response
No post tetanic potentiation
Potentiation by AChE inhibitors
Antagonism by Non-depolarizing blocker
Phase II block
Desensitization block
Prolonged succinylcholine
Desensitization of nicotinic RC
Channel block
No response
Non-depolarizing blocking like
effect
Antagonism by AChE inhibitor
• A = Non-depolarizing blockade … Fading
• B = Depolarizing blockade … No fading
• A = Post tetanic potentiation … Non-depolarizing blockade
• B = No post tetanic potentiation … Depolarizing blockade
Clinical Pharmacology of
Neuromuscular blockers
Muscle relaxation in surgery &
endotracheal tube insertion
In the past … use deep anesthesia
… Danger !... CNS depression
Neuromuscular blocker
No CNS depressant effect
Effects seen only with depolarizing
blockade (succinylcholine)
Hyperkalemia
Increased ocular pressure
Increased intragastric pressure
Muscle pain
Malignant hyperthermia
Drug Interaction
Depolarizing agent VS Non-depolarizing
agent
Antagonism
Non-depolarizing agent can prevent
fasciculation from depolarizing agent
Increase dose of succinylcholine ~ 5090%
Factors considered before
NMB selection
Duration of action
CVS effects
Elimination pathways
ADRs
Make yourself GOOD
LUCK for Mid-Term
Exam