Depolarizing NMJ blockers (depolarizing muscle relaxants)

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Fast onset, short duration

Agents

• Succinylcholine (suxamethonium)

Indications

• Anesthesia induction (esp. rapid sequence induction)

Monitoring

• Train-of-four stimulation shows an equal decrease in the amplitude of all 4 muscle twitches.
  • The muscle fiber becomes unresponsive to any further stimulation

Adverse effects

• Hyperkalemia
  • Mechanism: depolarization of large muscle groups → efflux of potassium ions into the extracellular space
  • Succinylcholine is contraindicated in case of hyperkalemia or in conditions associated with a high-risk of hyperkalemia, including:
    • Burn injuries
    • Rhabdomyolysis
• Prolonged muscle paralysis, respiratory depression and/or apnea in patients with a congenital deficiency of plasma cholinesterase
• Malignant hyperthermia

Nondepolarizing NMJ blockers (nondepolarizing muscle relaxants)

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Slow onset, long duration

Mechanism of action

• Compete with ACh to bind with the (nicotinic) ACh receptors at the motor end plate (competitive antagonists) → prevention of motor end plate depolarization (nondepolarization block)

Agents

• Rocuronium
• Vecuronium
• Atracurium

Indications

• Rapid-sequence induction of anesthesia when succinylcholine is contraindicated

Monitoring

• Train-of-four stimulation shows a fade-off in the amplitude of the muscle twitch
  • NDMRs block nicotinic acetylcholine receptors (nAChRs) not only at the postsynaptic membrane but also at presynaptic nerve terminals
  • These presynaptic receptors normally provide positive feedback for additional ACh release
  • When blocked, there’s reduced mobilization of ACh vesicles for subsequent stimuli