Succinylcholine (Suxamethonium)

Mechanism

Mechanism of action

Succinylcholine selectively binds to nicotinic cholinergic receptors (α₁β₁δε) located on the membrane of the postsynaptic motor end plate, behaving as a high affinity partial agonist.

Its initial binding causes the opening of the channel and a massive and prolonged depolarization of the muscle cell membrane, clinically manifested by transient involuntary contractions of the muscle bundles (fasciculations).

Since succinylcholine is not immediately degraded by acetylcholinesterase in the synaptic cleft, the motor end plate remains persistently depolarized and refractory to new cholinergic stimuli (Phase I Block), preventing the generation of new muscle action potentials.

Phase II Blockade by Receptor-Channel Desensitization

With the continued presence of succinylcholine in the synaptic cleft (repeated doses, overdoses or prolonged infusions), the neuromuscular plate undergoes a transition towards Phase II Blockade. In this phase, the terminal membrane repolarizes spontaneously due to the passive closure of the channels, but the nicotinic receptors remain desensitized and refractory to the choline excitatory stimulus. The Phase II blockade profile is identical to that of non-depolarizing relaxants, presenting fading upon train-of-four (TOF) stimulation and post-tetanic potentiation.

Pharmacokinetics

Pharmacokinetics and Metabolism

Succinylcholine has an ultrashort latency of 30 - 60 seconds after intravenous injection and a short clinical duration of 5 - 10 minutes. It is rapidly metabolized by the plasma enzyme pseudocholinesterase (plasma cholinesterase or butyrylcholinesterase) into succinylmonocholine and subsequently more slowly to inert choline and succinic acid. Only 10% of the injected dose actively reaches the actual neuromuscular neuromuscular junction.

Indicators and dose

Dosage and Clinical Use

• Rapid Sequence Induction (RSI): 1.0 - 1.5 mg/kg direct intravenous route.
• Prevention of Fasciculations: A low "pre-curing" dose of a non-depolarizing neuromuscular relaxant (1/10 of the ED95) can be administered one minute before the injection of succinylcholine to mitigate generalized muscle pain and myalgia upon awakening.

Security

Absolute Contraindications and Mortal Dangers

Risk of Hyperkalemia and Cardiac Arrest due to Denervation

The generalized opening of the muscle nicotinic receptor channels in a sustained manner promotes the massive passive outflow of cellular potassium into the extracellular space. Under normal conditions, serum potassium rises from 0.5 to 1.0 mEq/L. However, in patients with receptor deregulation due to denervation or extensive trauma (severe burns lasting more than 48 hours, spinal cord trauma with flaccid paralysis, degenerative myopathies such as Duchenne dystrophy or severe chronic sepsis), there is a massive proliferation of immature fetal-type nicotinic receptors (α₇) along the entire sarcolemmal surface. In these patients, the administration of succinylcholine can trigger a massive and uncontrollable release of intracellular potassium with acute elevations in serum potassium of up to 8 - 10 mEq/L, inducing fatal ventricular arrhythmias and immediate refractory asystole.

Pseudocholinesterase Deficiency and Prolongation of Blockade

Patients with homozygous atypical genetic variants of the pseudocholinesterase enzyme (such as the atypical cholinesterase gene or E1 locus mutation) have a functional inability to metabolize the drug. After receiving a standard induction dose, neuromuscular blockade can be prolonged for a period of 4 to 8 hours under supportive mechanical ventilation and continued active sedation in the ICU until spontaneous clearance of peripheral succinylcholine.