neuro muscular blockers

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  • 1. Neuromuscular Blockers
    • Competitive Antagonists of the Nicotinic Receptor
  • e.g. curare (d-tubocurarine), vecuronium, pancuronium, atracurium, etc
  • Depolarizing Blockers
  • e.g. succinylcholine, decamethonium 2. 3. 4. D-tubocurarine pancuronium Vecuronium Decamethonium Succinylcholine Depolarizing Blockers Competitive Blockers 5. Neuromuscular blockers differ from each other in:

  • Mechanism of action
  • Duration of action
  • Speed of onsetand offset of action
  • Selectivity of action and safety margin
  • Adverse effects 6. Classification of Blockers Agent Pharmacological Properties Onset time(min) Duration (min) Elimination Succinylcholine Ultrashort acting; Depolarizing 1-1.5 6-8 Plasma cholinesterase D-tubocurarine Long duration; Competitive 4-6 80-120 Renal and liver Atracurium Intermediate duration; Competitive 2-4 30-40 Plasma cholinesterase Mivacurium Short duration; Competitive 2-4 12-18 Plasma cholinesterase Pancuronium Long duration; Competitive 4-6 4-6 Renal and liver Rocuronium Intermediate duration; competitive 1-2 1-2 Renal and liver 7. Muscle AP Nerve AP Left LegMuscleStimulation Right LegNerveStimulation Right Leg Muscle Stimulation Site of Action of d-Tubocurarine 8. G: gallamine; TC: tubocurarine; NEO: neostigmine; S: succinylcholine. Non-depolarizing Block 9. Depolarizing Block C10: decamethonium TC: tubocurarine NEO: neostigmine S: succinylcholine 10. Comparison of Competitive and Depolarizing Blocking Agents Competitive Depolarizing Effect of previous d-tubocurarine Additive Antagonistic Effect of previous decamethonium None/antagonistic May be additive Efect of cholinesterase inhibitors Reverse No antagonism Effect on motor end plate Elevated threshold to Ach; no depolarization Partial, persisting depolarization Initial excitatory effect None Transient fasciculations Effect of KCl or tetatnus on block Transient reversal No antagonism 11. Dual Block by Depolarizing Agents C10: decamethonium; NEO: neostigmine; TC: tubocurarine NEO reversed the blockade by C10. 12. Depolarizing Blocker Competitive Blockade Competitive Blocker Noncompetitive Blockade (desensitization) (electrogenic Na pump) (direct channel block) Changing Nature of Neuromuscular Blockade 13. Sequence of Paralysis Fingers, orbit (small muscles) limbs Trunkneck Intercostals Diaphragm Recovery in Reverse 14. Other Effects of Neuromuscular Blockers

  • Action at Autonomic Ganglia
  • e.g. d-tubocurarine blocks,
  • succinylcholine may stimulate
  • newer agents have less ganglionic effects
  • Histamine Release
  • e.g. d-tubocurarine
  • bronchospasm, bronchial and salivary secretions 15. Adverse Effects/Toxicity

  • Hypotension
  • Decreased tone and motility in GI tract
  • Depolarizing agents can cause increased K efflux in patients with burns, trauma, or denervation and lead tohyperkalemia
  • Prolonged apnea (many reasons, check for pseudochlinesterase genetic polymorphism)
  • Malignant hyperthermia (succinylcholine + halothane especially)
  • Sinus bradycardia/junctional rhythm (with succinylcholine) 16. Systolic BP Systolic BP % Change in Systolic BP with d-Tubocurarineas a Function of Dose and Depth of Anesthesia Increasing Dose of d-tubocurarine Increasing Depth (% Halothane) 0.25% 0.5% 0.75% 6 mg/m 2 12 mg/m 2 18 mg/m 2 17. Influence of Type of Anesthetic on Enhancementof Neuromuscular Blockade By d-Tubocurarine 18. HR CO SVR MAP Hemodynamic Effects of d-Tubocurarine and Pancuronium 19. 20. Drug Interactions

  • Cholinesterase Inhibitors (antagonize competitive and enhance depolarizing)
  • Inhalational Anesthetics (synergistic)
  • Aminoglycoside Antibiotics (synergistic)
  • Calcium Channel Blockers (synergistic) 21. Therapeutic Uses

  • Adjuvant in surgical anesthesia
  • Orthopedic procedures for alignment of fractures
  • To facilitate intubations use one with a short duration of action
  • In electroshock treatment of psychiatric disorders