Neuromuscular Blocking Agents

งานนำเสนอเรื่อง: "Neuromuscular Blocking Agents"— ใบสำเนางานนำเสนอ:

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

2 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

3 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

4 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

5 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

6 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

7 Characteristic of Non-depolarizing blockers
No muscle fasciculation Tetanic fading Post tetanic potentiation Competitive binding with ACh Antagonism with “AChE inhibitor” … increased ACh

8 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

9 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

10 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

11 Phase II block Desensitization block Prolonged succinylcholine
Desensitization of nicotinic RC Channel block No response Non-depolarizing blocking like effect Antagonism by AChE inhibitor

12 A = Non-depolarizing blockade … Fading
B = Depolarizing blockade … No fading

13 A = Post tetanic potentiation … Non-depolarizing blockade
B = No post tetanic potentiation … Depolarizing blockade

14 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

15 Effects seen only with depolarizing blockade (succinylcholine)
Hyperkalemia Increased ocular pressure Increased intragastric pressure Muscle pain Malignant hyperthermia

16 Drug Interaction Depolarizing agent VS Non-depolarizing agent
Antagonism Non-depolarizing agent can prevent fasciculation from depolarizing agent Increase dose of succinylcholine ~ 50-90%

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

18 Make yourself GOOD LUCK for Mid-Term Exam