Neuromuscular Blocking Agents

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

2. วัตถุประสงค์เชิงพฤติกรรมวัตถุประสงค์เชิงพฤติกรรม • 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