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  1. 1. Neuromuscular Blockers <ul><li>Competitive Antagonists of the Nicotinic Receptor </li></ul><ul><li>e.g. curare (d-tubocurarine), vecuronium, pancuronium, atracurium, etc… </li></ul><ul><li>Depolarizing Blockers </li></ul><ul><li>e.g. succinylcholine, decamethonium </li></ul>
  2. 4. D-tubocurarine pancuronium Vecuronium Decamethonium Succinylcholine Depolarizing Blockers Competitive Blockers
  3. 5. Neuromuscular blockers differ from each other in: <ul><li>Mechanism of action </li></ul><ul><li>Duration of action </li></ul><ul><li>Speed of onset and offset of action </li></ul><ul><li>Selectivity of action and safety margin </li></ul><ul><li>Adverse effects </li></ul>
  4. 6. Classification of Blockers Renal and liver 1-2 1-2 Intermediate duration; competitive Rocuronium Renal and liver 4-6 4-6 Long duration; Competitive Pancuronium Plasma cholinesterase 12-18 2-4 Short duration; Competitive Mivacurium Plasma cholinesterase 30-40 2-4 Intermediate duration; Competitive Atracurium Renal and liver 80-120 4-6 Long duration; Competitive D-tubocurarine Plasma cholinesterase 6-8 1-1.5 Ultrashort acting; Depolarizing Succinylcholine Elimination Duration (min) Onset time (min) Pharmacological Properties Agent
  5. 7. Muscle AP Nerve AP Left Leg Muscle Stimulation Right Leg Nerve Stimulation Right Leg Muscle Stimulation Site of Action of d-Tubocurarine
  6. 8. G: gallamine; TC: tubocurarine; NEO: neostigmine; S: succinylcholine. Non-depolarizing Block
  7. 9. Depolarizing Block C10: decamethonium TC: tubocurarine NEO: neostigmine S: succinylcholine
  8. 10. Comparison of Competitive and Depolarizing Blocking Agents No antagonism Transient reversal Effect of KCl or tetatnus on block Transient fasciculations None Initial excitatory effect Partial, persisting depolarization Elevated threshold to Ach; no depolarization Effect on motor end plate No antagonism Reverse Efect of cholinesterase inhibitors May be additive None/antagonistic Effect of previous decamethonium Antagonistic Additive Effect of previous d-tubocurarine Depolarizing Competitive
  9. 11. Dual Block by Depolarizing Agents C10: decamethonium; NEO: neostigmine; TC: tubocurarine NEO reversed the blockade by C10.
  10. 12. Depolarizing Blocker Competitive Blockade Competitive Blocker Noncompetitive Blockade (desensitization) (electrogenic Na pump) (direct channel block) Changing Nature of Neuromuscular Blockade
  11. 13. Sequence of Paralysis Fingers, orbit (small muscles) limbs Trunk neck Intercostals Diaphragm Recovery in Reverse
  12. 14. Other Effects of Neuromuscular Blockers <ul><li>Action at Autonomic Ganglia </li></ul><ul><li>e.g. d-tubocurarine blocks, </li></ul><ul><li>succinylcholine may stimulate </li></ul><ul><li>newer agents have less ganglionic effects </li></ul><ul><li>Histamine Release </li></ul><ul><li>e.g. d-tubocurarine </li></ul><ul><li>bronchospasm, bronchial and salivary secretions </li></ul>
  13. 15. Adverse Effects/Toxicity <ul><li>Hypotension </li></ul><ul><li>Decreased tone and motility in GI tract </li></ul><ul><li>Depolarizing agents can cause increased K efflux in patients with burns, trauma, or denervation and lead to hyperkalemia </li></ul><ul><li>Prolonged apnea (many reasons, check for pseudochlinesterase genetic polymorphism) </li></ul><ul><li>Malignant hyperthermia (succinylcholine + halothane especially) </li></ul><ul><li>Sinus bradycardia/junctional rhythm (with succinylcholine) </li></ul>
  14. 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
  15. 17. Influence of Type of Anesthetic on Enhancement of Neuromuscular Blockade By d-Tubocurarine
  16. 18. HR CO SVR MAP Hemodynamic Effects of d-Tubocurarine and Pancuronium
  17. 20. Drug Interactions <ul><li>Cholinesterase Inhibitors (antagonize competitive and enhance depolarizing) </li></ul><ul><li>Inhalational Anesthetics (synergistic) </li></ul><ul><li>Aminoglycoside Antibiotics (synergistic) </li></ul><ul><li>Calcium Channel Blockers (synergistic) </li></ul>
  18. 21. Therapeutic Uses <ul><li>Adjuvant in surgical anesthesia </li></ul><ul><li>Orthopedic procedures for alignment of fractures </li></ul><ul><li>To facilitate intubations – use one with a short duration of action </li></ul><ul><li>In electroshock treatment of psychiatric disorders </li></ul>