KEY POINTS

1. Two different populations of nicotinic acetylcholine receptors are found at the mammalian neuromuscular junction. In the adult, the nicotinic acetylcholine receptor at the postsynaptic (muscular) membrane is composed of α₂ βδepsilon-subunits. Each of the two α-subunits has an acetylcholine-binding site. The presynaptic (neuronal) nicotinic receptor is also a pentameric complex composed of α₃ β₂ -subunits.
2. Nondepolarizing muscle relaxants produce neuromuscular blockade by competing with acetylcholine for the postsynaptic α-subunits. In contrast, succinylcholine produces prolonged depolarization that results in a decrease in sensitivity of the postsynaptic nicotinic acetylcholine receptor and inactivation of sodium channels so that propagation of the action potential across the muscle membrane is inhibited.
3. Different forms of neuromuscular stimulation test for neuromuscular blockade at different areas of the motor end plate. Depression of the response to single-twitch stimulation is probably due to blockade of postsynaptic nicotinic acetylcholine receptors, whereas fade in the response to tetanic and train-of-four stimuli results from blockade of presynaptic nicotinic receptors.
4. Succinylcholine is the only available depolarizing neuromuscular blocker. It has a rapid onset of effect and an ultrashort duration of action because of its rapid hydrolysis by butyrylcholinesterase.
5. The available nondepolarizing neuromuscular blockers can be classified according to chemical class (steroidal, benzylisoquinolinium, or other compounds) or according to onset or duration of action (long-, intermediate-, and short-acting drugs) of equipotent doses.
6. The speed of onset is inversely proportional to the potency of nondepolarizing neuromuscular blocking drugs. With the exception of atracurium, molar potency is highly predictive of a drug's rate of onset of effect. Rocuronium has a molar potency (ED₉₅ ≅ 0.54 µM/kg) that is about 13% that of vecuronium and 9% that of cisatracurium. Its onset of effect is more rapid than that of either of these agents.
7. Neuromuscular blockade develops faster, lasts a shorter time, and recovers more quickly in the more centrally located neuromuscular units (laryngeal adductors, diaphragm, and masseter muscle) than in the more peripherally located adductor pollicis.
8. The long-acting neuromuscular blockers undergo minimal or no metabolism, and they are primarily eliminated, largely unchanged, by renal excretion. Neuromuscular blockers of intermediate duration of action have a more rapid clearance than the long-acting agents do because of multiple pathways of degradation, metabolism, and/or elimination. Mivacurium (a short-acting neuromuscular blocker) is cleared rapidly and almost exclusively by means of metabolism by butyrylcholinesterase.
9. After the administration of nondepolarizing neuromuscular blocking drugs, it is essential to ensure adequate return of normal neuromuscular function. Residual paralysis decreases upper esophageal tone, coordination of the esophageal musculature during swallowing, and the hypoxic ventilatory drive.
10. Defects in ion channels (channelopathies) in the presynaptic (neuronal) or postsynaptic (muscular) membrane of the neuromuscular junction result in a wide spectrum of muscle diseases.