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Blocking Agents
Pawitra Pulbutr
M.Sc. In Pharm (Pharmacology)
วัตถุประสงค ์เชิง
พฤติกรรม
• นิ สต
ิ มีความรู ้ความเข้าใจถึง
เภสัชวิทยา กลไกการออกฤทธิ ์
เภสัชจลนศาสตร ์ การใช้
ประโยชน์ทางคลินิก อาการไม่
พึงประสงค ์ และปฏิก ิรย ิ า
ระหว่างยา ของยาหย่อน
้
กล้ามเนื อชนิ ด Non-depolarizing
blocking agents และ Depolarizing
Muscle relaxing drugs
• Neuromuscular blocking agents
– 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
• Junction b/w motor
nerve nerve terminal
(somatic nerve) and
skeletal muscle
NMJ
• 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 Non-
depolarizing 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
• 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
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 ~ 50-
90%
Factors considered before
NMB selection
Duration of action
CVS effects
Elimination pathways
ADRs
Make yourself GOOD
LUCK for Mid-Term
Exam