Mechanism of Action and Clinical Presentation
Succinylcholine binds to $N_M$ cholinergic receptors at the skeletal muscle motor endplate as an agonist. Similar to endogenous acetylcholine, it causes depolarization of the postsynaptic membrane. However, the drug is resistant to synaptic acetylcholinesterase and is virtually not degraded within the synaptic cleft. Prolonged presence of the substance in the synapse triggers persistent membrane depolarization, making the conduction of new nerve impulses impossible.
Clinically, the drug's effect occurs in two phases:
- Fasciculation phase: Initial muscle twitches due to the primary contraction of muscle fibers.
- Relaxation phase: Complete relaxation of skeletal musculature.
Interaction with Anticholinesterase Agents
A crucial rule: anticholinesterase agents (e.g., neostigmine) are not antagonists of succinylcholine. On the contrary, they exhibit marked synergism, enhancing and prolonging the neuromuscular block.
Potentiation of the effect occurs via two mechanisms:
- At the receptor level: Enzyme inhibition increases the concentration of endogenous acetylcholine, which does not reverse the block but further deepens membrane depolarization.
- At the metabolic level: Anticholinesterase drugs block plasma cholinesterase (pseudocholinesterase), the sole enzyme capable of hydrolyzing succinylcholine into choline and succinic acid.
Clinical Uses and the 'Dual Block' Phenomenon
The drug is used exclusively for short-term muscle relaxation (up to 10 minutes). It is utilized in anesthesiology for endotracheal intubation, during endoscopic procedures (bronchoscopy, cystoscopy), short surgical interventions (reduction of dislocations, bone fracture repositioning), and for controlling tonic spasms in tetanus.
With frequent repeated administrations of succinylcholine, a 'dual block' phenomenon may develop. $N_M$ receptor desensitization occurs, and the depolarizing block transitions into an antidepolarizing (nondepolarizing) block. Only during this unique phase can the administration of anticholinesterase agents weaken the muscle-paralyzing effect of the drug.
Side Effects and Contraindications
The use of succinylcholine carries a high risk of adverse reactions and severe muscular complications, including rhabdomyolysis and myoglobinemia.
- Myalgias: Postoperative muscle pains occur due to microtrauma to muscles during the fasciculation period.
- Electrolyte disturbances: The efflux of $K^+$ ions from cells during persistent depolarization leads to hyperkalemia, creating a risk of fatal arrhythmias and cardiac arrest.
- Autonomic responses: Stimulation of muscarinic ($M$) receptors causes bradycardia and hypersalivation, while excitation of nicotinic ($N$) receptors in sympathetic ganglia causes hypertension.
- Ophthalmologic effects: Tonic contraction of extraocular muscles disrupts the outflow of aqueous humor, increasing intraocular pressure.
The most dangerous complication is malignant hyperthermia. This is a life-threatening massive release of calcium ions from the sarcoplasmic reticulum (especially when combined with halotan/volatile anesthetics), leading to tonic muscle spasm and temperature spikes up to 42 °C. Dantrolene, a calcium release blocker, is used for treatment.
Due to its broad spectrum of adverse reactions, the drug is strictly contraindicated in glaucoma, liver dysfunction (the site of pseudocholinesterase synthesis), anemia, pregnancy, and infancy.