depolarizing neuromuscular blocker

MECHANISM: Succinylcholine = two ACh molecules joined. It binds and activates nicotinic (Nm) receptors at the neuromuscular junction, opening the channel and causing sustained end-plate depolarization. Voltage-gated Na+ channels adjacent to the end plate become inactivated (they stay in the inactivated state while the membrane remains depolarized), so the muscle cannot repolarize and fire again. Result: initial fasciculations, then flaccid paralysis.

PHASES: Phase I (depolarizing) block: occurs with a single dose or low-dose infusion. It is potentiated by acetylcholinesterase inhibitors (neostigmine) and is not reversed by them. Phase II (desensitizing) block: occurs with high doses or prolonged infusion. The receptor becomes desensitized and the block resembles a nondepolarizing block. It may be partially reversed by AChE inhibitors.

PHARMACOKINETICS: IV onset ~30-60 sec, duration ~5-10 min. Metabolized by plasma pseudocholinesterase (butyrylcholinesterase) to succinylmonocholine, then more slowly to succinic acid and choline. Muscle paralysis pattern: motor weakness first, then fasciculations; the diaphragm is relatively resistant and is paralyzed last. Recovery is by diffusion away from the end plate, not by enzyme action at the junction.

CLINICAL USE: Rapid sequence intubation (fastest onset), short procedures, and ECT (to reduce convulsive injury).

ADVERSE EFFECTS (high-yield): 1. Hyperkalemia: K+ release from depolarized muscle. It is dangerous in burns (after ~24-48 h), crush/major trauma, denervation injury (spinal cord injury, stroke, prolonged immobilization), and neuromuscular disease (Duchenne/Becker muscular dystrophy, upregulated extrajunctional AChR). It can cause arrhythmias and cardiac arrest, and is also a concern in chronic renal failure with baseline hyperkalemia. 2. Malignant hyperthermia: with volatile anesthetics (halothane, sevoflurane, isoflurane). Mutation in RYR1 (ryanodine receptor) or CACNA1S, autosomal dominant. Causes uncontrolled Ca2+ release from the SR, hypercarbia (rising end-tidal CO2), rigidity, hyperthermia, rhabdomyolysis, and acidosis. Treatment: dantrolene (blocks RyR1) and cooling, stop triggers. 3. Prolonged paralysis (Phase I block lasting hours): in patients with pseudocholinesterase deficiency (atypical/dibucaine-resistant BCHE variant, liver disease, pregnancy, drug inhibition). Dibucaine number is low in atypical enzyme. Treat with supportive ventilation until the drug wears off (fresh frozen plasma or purified enzyme are options). 4. Bradycardia/asystole: muscarinic stimulation (especially with repeat dosing or in children). Pretreat with atropine. 5. Increased intraocular, intragastric, and intracranial pressure: caution in open-globe injury. Fasciculations can cause postoperative myalgias. 6. Masseter spasm: may be an early sign of malignant hyperthermia. 7. Anaphylaxis: succinylcholine is among the more common NMB causes.

CONTRAINDICATIONS: Personal/family history of malignant hyperthermia, hyperkalemia risk (burns, crush, denervation, myopathies), known pseudocholinesterase deficiency, and open-globe injury or raised ICP (relative).

COMPARISON WITH NONDEPOLARIZING AGENTS (e.g., rocuronium, vecuronium, cisatracurium, atracurium, pancuronium; "-curium/-curonium"): These are competitive nicotinic antagonists. They cause no fasciculations, and their block is reversed by AChE inhibitors (neostigmine, edrophonium) or by sugammadex (encapsulates rocuronium/vecuronium). Nondepolarizing agents have slower onset (except rocuronium, which is the alternative for RSI). The block is overcome by increasing ACh at the junction. Cisatracurium and atracurium undergo Hofmann elimination (organ-independent), which is useful in renal and hepatic failure. Atracurium can release histamine; its metabolite laudanosine can cause seizures.

OTHER NOTES: Decamethonium is another depolarizing agent (rarely used). Myasthenia gravis patients are resistant to depolarizing agents (fewer AChRs) but sensitive to nondepolarizing ones. Lambert-Eaton patients are sensitive to both. Monitor with train-of-four: Phase I has no fade and no post-tetanic potentiation (PTP), whereas nondepolarizing block and Phase II show fade with PTP.