Depolarizing agents

1. Mechanism of action:

The depolarizing neuromuscular blocking drug succinylcholine [suk-sin-ill-KOE-leen] attaches to the nicotinic receptor and acts like acetylcholine to depolarize the junction.

Figure : Mechanism of action of depolarizing neuromuscular blocking drugs.


Unlike acetylcholine, which is instantly destroyed by acetylcholinesterase, the depolarizing agent persists at high concentrations in the synaptic cleft, remaining attached to the receptor for a relatively longer time and providing a constant stimulation of the receptor. [Note: The duration of action of succinylcholine is dependent on diffusion from the motor end plate and hydrolysis by plasma cholinesterase.].

 The depolarizing agent first causes the opening of the sodium channel associated with the nicotinic receptors, which results in depolarization of the receptor (Phase I). This leads to a transient twitching of the muscle (fasciculations). Continued binding of the depolarizing agent renders the receptor incapable of transmitting further impulses. With time, continuous depolarization gives way to gradual repolarization as the sodium channel closes or is blocked. This causes a resistance to depolarization (Phase II) and a flaccid paralysis.

2. Actions:

The sequence of paralysis may be slightly different, but as with the competitive blockers, the respiratory muscles are paralyzed last. Succinylcholine initially produces short-lasting muscle fasciculations, followed within a few minutes by paralysis. The drug does not produce a ganglionic block except at high doses, but it does have weak histamine-releasing action. Normally, the duration of action of succinylcholine is extremely short, because this drug is rapidly broken down by plasma cholinesterase.

 However, succinylcholine that gets to the neuromusclular junction is not metabolized by acetylcholinesterase, allowing the agent to bind to nicotinic receptors, and redistribution to plasma is necessary for metabolism (therapeutic benefits last only for a few minutes). [Note: Genetic variants in which plasma cholinesterase levels are low or absent leads to prolonged neuromuscular paralysis

3. Therapeutic uses: 

 Because of its rapid onset and short duration of action, succinylcholine is useful when rapid endotracheal intubation is required during the induction of anesthesia (a rapid action is essential if aspiration of gastric contents is to be avoided during intubation). It is also employed during electroconvulsive shock treatment.


4. Pharmacokinetics:

Succinylcholine is injected intravenously. Its brief duration of action (several minutes) results from redistribution and rapid hydrolysis by plasma cholinesterase. It therefore is usually given by continuous infusion.


 5. Adverse effects

a. Hyperthermia: When halothane  is used as an anesthetic, administration of succinylcholine has occasionally caused malignant hyperthermia (with muscular rigidity and hyperpyrexia) in genetically susceptible people . This is treated by rapidly cooling the patient and by administration of dantrolene, which blocks release of Ca2+ from the sarcoplasmic reticulum of muscle cells, thus reducing heat production and relaxing muscle tone

b. Apnea: Administration of succinylcholine to a patient who is genetically deficient in plasma cholinesterase or has an atypical form of the enzyme can lead to prolonged apnea due to paralysis of the diaphragm. c. Hyperkalemia: Succinylcholine increases potassium release from intracellular stores. This may be particularly dangerous in burn patients or patients with massive tissue damage in which postassium is been rapidly lost from within cells.

back to cholinergic antagonist