Neuromuscular Blocking Agents Pawitra Pulbutr M.Sc. In Pharm (Pharmacology)

วัตถุประสงค์เชิงพฤติกรรม นิสิตมีความรู้ความเข้าใจถึงเภสัชวิทยา กลไกการออกฤทธิ์ เภสัชจลนศาสตร์ การใช้ประโยชน์ทางคลินิก อาการไม่พึงประสงค์ และปฏิกิริยาระหว่างยา ของยาหย่อนกล้ามเนื้อชนิด Non-depolarizing blocking agents และ Depolarizing blocking agents นิสิตมีความเข้าใจถึงความแตกต่างของการตอบสนองของกล้ามเนื้อต่อ ยาหย่อนกล้ามเนื้อชนิด Non-depolarizing blocking agents และ 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) Junction b/w motor nerve terminal (somatic nerve) and skeletal muscle NTs = Acetylcholine (ACh) Motor end plate contain Nicotinic Receptor & AChE Motor nerve NMJ

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 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 ~ 50-90%

Factors considered before NMB selection Duration of action CVS effects Elimination pathways ADRs

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