Depolarizing NMJ blockers (depolarizing muscle relaxants)

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
  • AChE ("True Cholinesterase"):
    • Function: Rapidly hydrolyzes acetylcholine (ACh) in synaptic clefts & neuromuscular junctions (NMJs) to terminate neurotransmission. Essential for precise control of nerve impulses.
    • Location: Primarily at postsynaptic NMJs, cholinergic synapses in CNS, red blood cells.
  • PChE (Butyrylcholinesterase, "Plasma/Serum Cholinesterase"):
    • Function: Hydrolyzes exogenous choline esters (e.g., succinylcholine, mivacurium) and some local anesthetics (e.g., procaine, cocaine). Physiological role not fully understood, but may be involved in nerve signal transmission.
    • Location: Synthesized in the liver; found in plasma, liver, pancreas, heart, brain (white matter).
    • Atypical pseudocholinesterase
      • Pseudocholinesterase is responsible for the breakdown of succinylcholine through ester hydrolysis.
      • Atypical pseudocholinesterase breaks down succinylcholine slowly and thus prolongs the duration of muscle relaxation during anesthesia from a few minutes to a few hours; this may cause respiratory depression.
• Malignant hyperthermia

Nondepolarizing NMJ blockers (nondepolarizing muscle relaxants)

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