Classification and mechanism of action
According to their mechanism of action on receptors, muscle relaxants are divided into two fundamentally different groups. Their main difference is the ability to cause depolarization of the postsynaptic membrane.
| Characteristic | Nondepolarizing (competitive) | Depolarizing |
|---|---|---|
| Mechanism | Competitive receptor blockade, prevention of depolarization | Persistent receptor stimulation causing prolonged depolarization |
| Clinical presentation | Instantaneous muscle relaxation (myorelaxation) | First muscle twitching (fasciculations), then relaxation |
| Interaction with AChE | Antagonism (block is reversed) | Synergism (block is enhanced and prolonged) |
Nondepolarizing agents act as classical competitive antagonists. They occupy the receptor, preventing endogenous acetylcholine from binding to it. No binding means no depolarization, and the muscle fiber does not contract. Since the block is competitive, it can be overcome by artificially increasing the concentration of the neurotransmitter in the synaptic cleft.
Decurarization: how to restore muscle tone
The process of pharmacologic reversal of neuromuscular block is called decurarization. Two groups of drugs are used to eliminate the effect of nondepolarizing muscle relaxants:
- Anticholinesterase agents (AChEIs). A classic example is neostigmine. It acts as a functional antagonist: it inhibits the enzyme acetylcholinesterase, causing acetylcholine to accumulate in the synapse and literally "displace" the muscle relaxant from its receptor binding. In addition, neostigmine has a direct stimulating effect on N-cholinergic receptors. Edrophonium, a short-acting drug, is also used for these purposes.
- Specific antagonists. The modern standard is sugammadex. It works completely differently: it does not affect enzymes or receptors, but directly binds to rocuronium or vecuronium molecules, enclosing them in a capsule. This makes sugammadex the drug of choice for rapid and safe restoration of neuromuscular conduction (in children aged 2–17 years, it is used only to reverse rocuronium blockade).
Clinical nuances and dangerous interactions
When working with muscle relaxants, it is important to consider comorbid conditions and medications taken by the patient. The effect of nondepolarizing agents can unpredictably increase in the presence of hypothermia, electrolyte imbalances (especially hypokalemia), as well as with the administration of magnesium preparations, aminoglycoside antibiotics, and inhalation anesthetics (halothane, sevoflurane).
Patients with myasthenia gravis require special attention. Due to altered sensitivity of synapses, depolarizing muscle relaxants are contraindicated in them. Preference is given to short-acting nondepolarizing drugs (e.g., rocuronium). Timely decurarization with sugammadex in such patients is critically important, as it reliably reduces the risk of postoperative myasthenic crisis (for example, after thymectomy).
Strict contraindication: attempting to reverse block from depolarizing muscle relaxants (succinylcholine) using AChEIs. In this case, the drugs will act as synergists, and the paralysis will only be prolonged.
To avoid confusing interactions, remember: "Anti" works against "Anti". Antidepolarizing muscle relaxants and anticholinesterase agents are antagonists (they reverse the block). But with depolarizing drugs, AChEIs act as synergists.
Class and exam questions
Why do anticholinesterase agents enhance the effect of depolarizing muscle relaxants?
A dual mechanism is at work here. First, the accumulated acetylcholine itself maintains persistent membrane depolarization. Second, AChEIs inhibit plasma pseudocholinesterase, the enzyme that normally degrades the depolarizing muscle relaxant, thereby slowing down its metabolism.
What is the uniqueness of the mechanism of action of sugammadex?
Sugammadex does not interfere with the functioning of the synapse, receptors, or enzymes. It forms a stable complex directly with the muscle relaxant molecule (rocuronium or vecuronium), encapsulating it and rendering it inactive.
Which muscle relaxants are safer to use in myasthenia gravis?
In myasthenia gravis, depolarizing agents should be avoided. The drugs of choice are short-acting nondepolarizing muscle relaxants, the effect of which is then reliably reversed by specific antagonists.
What else to study on this topic
- Molecular structure of the active centers of acetylcholinesterase
- Differential diagnosis of myasthenic and cholinergic crises
- Pharmacokinetics of cholinesterase reactivators in organophosphate poisoning
- Selection of centrally acting anticholinesterase drugs in Alzheimer's disease
- Ganglionic blockers: effect on N-cholinergic receptors of autonomic ganglia
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