Learning Objective

By the end of this note, you should be able to differentiate non-depolarizing and depolarizing neuromuscular blockers, describe their mechanism, clinical features, and reversal, and recognize key drug-specific characteristics relevant for exams.

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Nondepolarizing (Competitive) Nicotinic Antagonists

Prototype: Rocuronium

Mechanism

• Competitive antagonists of nicotinic NM receptors at the neuromuscular junction.
• Prevent ACh binding → flaccid paralysis.

Reversal

• Reversible by AChE inhibitors (neostigmine, edrophonium), which ↑ inhibit ACh at the NMJ.
• TOF (train-of-four) shows fade due to presynaptic inhibition of ACh release.

Paralysis Progression

• Face muscles
• Limbs
• Respiratory muscles

Effects: No effects on:

• Cardiac muscle
• Smooth muscle
• CNS (they are quaternary ammonium compounds)

Specific agents

• Atracurium
  • Undergoes Hofmann elimination: safe in hepatic/renal impairment
  • Breaks down to laudanosine, which may cause seizures
• Cisatracurium
  • Forms less laudanosine → safer profile

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Activity

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Depolarizing (Noncompetitive) Nicotinic Agonist

Prototype: Succinylcholine

Mechanism

Binds NM receptor → persistent depolarization → paralysis.

Phases

Phase I Block (Depolarizing)

• Fasciculations → prolonged depolarization → flaccid paralysis
• No fade in train-of-four
• AChE inhibitors worsen the Phase I (↑ succinylcholine effect)

Phase II Block (Desensitization)

• The end plate repolarizes but becomes desensitized
• AChE inhibitors may reverse Phase II

Metabolism

• Rapidly hydrolyzed by pseudocholinesterase → very short duration
• Prolonged paralysis occurs in pseudocholinesterase deficiency

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Activity