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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 onset and 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 Leg Muscle Stimulation Right Leg Nerve Stimulation 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 Trunk neck 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 to hyperkalemia
    • 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-Tubocurarine as 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 Enhancement of 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