Succinylcholine

Toxicity

Overdosage of succinylcholine is likely to extend the neuromuscular blockade beyond the time needed for surgery. Symptoms are likely to be consistent with its therapeutic effects, although more pronounced, and may therefore include skeletal muscle weakness, decreased respiratory reserve, low tidal volume, or apnea. Treatment of succinylcholine overdose involves airway and respiratory support until recovery of normal respiration is assured.
Depending on the extent of the overdose, the characteristic depolarizing (i.e. Phase I) neuromuscular blockade may switch to resemble more closely a non-depolarizing (i.e. Phase II) neuromuscular blockade. This occurs primarily when succinylcholine is given over a prolonged period of time or with particularly large doses, and may result in significant respiratory muscle paralysis or weakness.

Description

Succinylcholine is the only therapeutically used depolarizing neuromuscular blocker. Unlike nondepolarizing substances, succinylchloride is not a competitive antagonist; conversely, it is a more stable agonist than acetylcholine. In this manner, succinylcholine differs from acetylcholine only in duration—it lasts longer, causing a more stable depolarization. Thus the process of repolarization is blocked and the muscles relax. During this period, muscles that cause fine movement (ocular, facial, neck) are the most sensitive and are blocked first, after which muscles of the extremities are blocked, and finally the most stable respiratory muscles. Restoration occurs upon completion of drug action.

Originator

Anectine,Glaxo Wellcome

The Uses of Succinylcholine

Therapeutic use of succinylcholine consists of preventing involuntary patient movement. It is used for brief operations, intubation of the trachea, and other endoscopic procedures. Synonyms of this drug are listenon, midarine, sucostrin, ditilin, and others.

Background

Succinylcholine is a depolarizing skeletal muscle relaxant consisting of two molecules of the endogenous neurotransmitter acetylcholine (ACh) linked by their acetyl groups. It has been widely used for over 50 years, most commonly in its chloride salt form, as a means of neuromuscular blockade during intubation and surgical procedures. Its rapid onset and offset, with effects beginning within 60 seconds of intravenous administration and lasting between four to six minutes, make succinylcholine particularly useful in the setting of short medical procedures requiring brief periods of muscle relaxation.

Indications

Succinylcholine is indicated as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Definition

ChEBI: A quaternary ammonium ion that is the bis-choline ester of succinic acid.

Manufacturing Process

For the first time Fusko with coworkers synthesied the succinylcholine in 1949 year.
By the etherification of succinic acid chloroanhydride with dimethylaminoethanol hydrochloride in the presence of sodium hydroxide succinylcholine was prepared. Then the obtained succinylcholine was purified. To the succinylcholine the methylchloride was added (1:2 mols) and the succinylcholine dichloride was obtained as white powder.
The succinylcholine is used as succinylcholine diiodide. This salt may be prepeared identicaly.

Therapeutic Function

Muscle relaxant

Pharmacokinetics

Succinylcholine's neuromuscular blockade takes effect within 60 seconds of intravenous administration and lasts between four to six minutes. Similar to acetylcholine, it binds to cholinergic receptors of the motor endplate to induce membrane depolarization and, eventually, muscle paralysis, which may be maintained for as long as an adequate concentration of succinylcholine remains at the receptor site. Succinylcholine has no direct action on smooth or cardiac muscle, nor does it appear to act on pre-synaptic or ganglionic acetylcholine receptors. The paralysis induced by succinylcholine has been described as "progressive", first involving the muscles of the face and glottis, then the intercostals and diaphragm, then followed by other skeletal muscles.
Succinylcholine has no effect on consciousness or pain threshold, and must therefore be used in conjunction with adequate anesthesia. There have been rare reports of the development of acute rhabdomyolysis with hyperkalemia - resulting in ventricular dysrhythmias, cardiac arrest, and death - after the intravenous administration of succinylcholine to apparently healthy pediatric patients who were subsequently found to have undiagnosed skeletal myopathy (most frequently Duchenne's muscular dystrophy). Infants or children experiencing seemingly idiopathic cardiac arrest soon after the administration of succinylcholine should therefore be treated immediately for hyperkalemia. Given that patients may not present with any apparent risk factors, the use of succinylcholine in pediatric patients should be restricted to emergency intubation or other situations in which a suitable alternative is unavailable.

Synthesis

Succinylcholine, 2,2-[(1,4-dioxo-1,4-butanediyl)bis(oxy)]bis[N,N,Ntrimethylethanaminium( diacetylcholine)] dichloride, which can be viewed as a dimeric molecule of acetylcholine (diacetylcholine), is synthesized by reacting succinic acid dichloride with 2-dimethylaminoethanol and subsequent transformation of the resulting bis-(2-dimethylaminoethyl) succinate (15.1.13) into a quaternary salt, succinylcholine (15.1.14).

Metabolism

Succinylcholine is rapidly metabolized by plasma cholinesterase in the bloodstream to succinylmonocholine, which is then further hydrolyzed (albeit more slowly) to succinic acid and choline.