USMLE

Succinylcholine

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Anesthetics
  1. Ketamine
  2. Nitrous Oxide (N2O)
  3. Local Anesthetics
  4. Nondepolarizing Neuromuscular-blocking Drugs
  5. Succinylcholine
  6. Halothane and Fluranes
  7. Propofol
  8. Thiopental

Summary

Succinylcholine is a depolarizing neuromuscular junction blocker used to cause paralysis during anesthesia. It acts by agonizing nicotinic acetylcholine receptors, which in turn causes continuous depolarization at the motor end plate. Initially, phase I block causes total depolarization and blockage of muscle contractions, which can be visualized as equal reductions on train of four stimulation. With continued administration, this transitions to phase II block, where the cell becomes repolarized but desensitized, which is visualized as progressive reduction on train of four stimulation. During phase II block, neostigmine can be administered to reverse paralysis. Don't forget the adverse effects of succinylcholine, which include hyperkalemia and dangerously, malignant hyperthermia.

Key Points

  • Succinylcholine (Depolarizing Paralytic)
    • Mechanism
      • Agonist at nicotinic receptors
        • Continuous depolarization at neuromuscular junction causes paralysis by not allowing muscle to repolarize
        • Phase I: depolarized
          • Depolarization isolated to the end plate, resulting in flaccid paralysis (can manifest as transient fasciculations)
          • No antidote/reversal
            • Unlike ACh, succinylcholine is not degraded by acetylcholinesterases
          • Train of Four (TOF) stimulation shows equal reduction of all 4 twitches
        • Phase II: repolarized but desensitized
          • Nicotinic receptors become desensitized to succinylcholine, allowing gradual repolarization.
          • Reversible by AChE inhibitors (e.g. neostigmine)
            • Because ACh receptors ARE available, we can increase the ACh concentration to overcome desentization
          • Train of Four (TOF) stimulation shows progressive reduction in each of the 4 twitches
            • Similar to nondepolarizing block
    • Clinical Use
      • Paralysis for Anesthesia
        • Diminished reflexes help with surgery or endotracheal intubation
        • Fast-acting (<1 min) onset used for rapid-sequence intubation (fast intubations)
    • Adverse Effects
      • Malignant hyperthermia
        • Hypersensitivity of skeletal muscles due to defect on ryanodine receptors on SR
        • Causes calcium influx and excessive muscle contraction with high body temperature and rigidity
        • Treat with dantrolene (ryanodine receptor antagonist)
      • Hyperkalemia
        • Because nicotinic receptors are non-selective cation channels, their opening also allows potassium release (not just sodium influx)
        • High risk in patients with crash, crush, or burn injuries, myopathies, tissue damage, and denervating injuries/diseases (quadriplegia, GBS)
      • Prolonged paralysis
        • Succinylcholine is degraded by pseudocholinesterase; deficiency of pseudocholinesterase causes prolonged blockade that lasts for hours
        • Patients must stay on mechanical ventilation until spontaneous respirations resume
      • Hypercalcemia