Mechanism of Action: Succinylcholine vs Rocuronium
Succinylcholine is a depolarizing neuromuscular blocking agent that acts as an agonist at nicotinic receptors, causing ion channels to open and remain open, resulting in initial depolarization (seen as fasciculations) followed by paralysis, while rocuronium is a nondepolarizing competitive antagonist that binds to nicotinic receptors and prevents acetylcholine from binding, producing neuromuscular blockade without depolarization. 1, 2
Succinylcholine: Depolarizing Mechanism
Succinylcholine physically resembles acetylcholine and binds to and activates nicotinic acetylcholine receptors at the motor endplate 1
The drug causes ion-gated channels to open and remain open in the presence of succinylcholine, producing sustained depolarization 1
The initial depolarization is clinically observed as muscle fasciculations, followed by paralysis as the endplate becomes refractory to further acetylcholine stimulation 1, 3
Duration of effect is only 3-5 minutes because succinylcholine is rapidly metabolized by pseudocholinesterase 1, 3
The brief duration makes it ideal for short procedures like rapid sequence intubation, with onset time of approximately 50 seconds 4
Rocuronium: Nondepolarizing Mechanism
Rocuronium is a nondepolarizing neuromuscular blocking agent that acts by competing for cholinergic receptors at the motor endplate 2
It functions as a competitive antagonist at nicotinic receptors, binding to the receptor for a longer period and preventing acetylcholine from binding, which results in prolonged neuromuscular blockade 1
Unlike succinylcholine, rocuronium does not activate the receptors—it simply blocks acetylcholine from binding without causing depolarization 1, 3
As the concentration of rocuronium increases relative to acetylcholine, neuromuscular transmission is progressively compromised 3
The onset time is dose-dependent: 0.9 mg/kg produces onset in approximately 75 seconds, while 1.2 mg/kg produces onset in 55 seconds, comparable to succinylcholine 4
Clinical duration is significantly longer than succinylcholine (30-60 minutes vs 3-5 minutes) 5, 4
Reversal Mechanisms
Rocuronium's action can be pharmacologically reversed with acetylcholinesterase inhibitors (neostigmine, edrophonium) which increase acetylcholine concentration to compete with the drug at nicotinic receptors 1, 2
Alternatively, sugammadex can reverse rocuronium by directly encapsulating and binding the rocuronium molecules, removing them from the neuromuscular junction 6
Succinylcholine does not require pharmacological reversal due to its rapid metabolism by pseudocholinesterase 1
Clinical Implications of Different Mechanisms
In conditions causing nicotinic receptor upregulation (burns, denervation, prolonged immobilization), succinylcholine produces exaggerated depolarization with massive potassium efflux, potentially causing life-threatening hyperkalemia 5, 7
These same conditions cause resistance to nondepolarizing agents like rocuronium because more receptors must be blocked to achieve paralysis 1, 7
The American Society of Anesthesiologists recommends rocuronium at doses ≥0.9 mg/kg as an alternative to succinylcholine for rapid sequence intubation in high-risk patients due to its safer profile 5
Rocuronium's quaternary ammonium structure makes it lipophobic and unable to cross the blood-brain barrier, limiting central nervous system effects 1