Skip to Main Content

The drugs in this chapter are divided into 2 dissimilar groups. The neuromuscular blocking drugs, which act at the skeletal myoneural junction, are used to produce muscle paralysis to facilitate surgery or assisted ventilation. The spasmolytic drugs, most of which act in the CNS, are used to reduce abnormally elevated tone caused by neurologic or muscle end plate disease.


| Download (.pdf) | Print
Depolarizing blockadeNeuromuscular paralysis that results from persistent depolarization of the end plate (eg, by succinylcholine)
DesensitizationA phase of blockade by a depolarizing blocker during which the end plate repolarizes but is less than normally responsive to agonists (acetylcholine or succinylcholine)
Malignant hyperthermiaHyperthermia that results from massive release of calcium from the sarcoplasmic reticulum, leading to uncontrolled contraction and stimulation of metabolism in skeletal muscle
Nondepolarizing blockadeNeuromuscular paralysis that results from pharmacologic antagonism at the acetylcholine receptor of the end plate (eg, by tubocurarine)
SpasmolyticA drug that reduces abnormally elevated muscle tone (spasm) without paralysis (eg, baclofen, dantrolene)
Stabilizing blockadeSynonym for nonpolarizing blockade

Classification and Prototypes

Skeletal muscle contraction is evoked by a nicotinic cholinergic transmission process. Blockade of transmission at the end plate (the postsynaptic structure bearing the nicotinic receptors) is clinically useful in producing muscle relaxation, a requirement for surgical relaxation, tracheal intubation and control of ventilation. The neuromuscular blockers are quaternary amines structurally related to acetylcholine (ACh). Most are antagonists (nondepolarizing type), and the prototype is tubocurarine. One neuromuscular blocker used clinically, succinylcholine, is an agonist at the nicotinic end plate receptor (depolarizing type).

Nondepolarizing Neuromuscular Blocking Drugs


All agents are given parenterally. They are highly polar drugs and do not cross the blood-brain barrier. Drugs that are metabolized (eg, mivacurium, by plasma cholinesterase) or eliminated in the bile (eg, vecuronium) have shorter durations of action (10–20 min) than those eliminated by the kidney (eg, metocurine, pancuronium, pipecuronium, and tubocurarine), which usually have durations of action of less than 35 min. In addition to hepatic metabolism, atracurium clearance involves rapid spontaneous breakdown (Hofmann elimination) to form laudanosine and other products. At high blood levels, laudanosine may cause seizures. Cisatracurium, a stereoisomer of atracurium, is also inactivated spontaneously but forms less laudanosine and currently is one of the most commonly used muscle relaxants in clinical practice.

Mechanism of Action

Nondepolarizing drugs prevent the action of ACh at the skeletal muscle end plate (Figure 27–1). They act as surmountable blockers. (That is, the blockade can be overcome by increasing the amount of agonist [ACh] in the synaptic cleft.) They behave as though they compete with ACh at the receptor, and their effect is reversed by cholinesterase inhibitors. Some drugs in this group may also act directly to plug the ion channel operated by the ACh ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.