Neuromuscular Blocking Agents

Pawitra Pulbutr M.Sc. In Pharm (Pharmacology)


Nondepolarizing blocking agents Depolarizing blocking agents Non-depolarizing blocking agents Depolarizing blocking agents

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 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 Phase II block
depolarizing 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

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