Suxamethonium -Depolarizing Neuromuscular Blocker

Suxamethonium is the only drug used in the category of depolarizing neuromuscular blockers and is synthetic, consisting of 2 molecules of acetyl choline joined together.

Mechanism of Action

It binds to post-synaptic nicotinic receptors, activating them and opening ion channels, which causes depolarization and contraction.

Phase I Block

In contrast to acetyl choline, which is hydrolyzed in synaptic cleft, this suxamethonium is not rapidly metabolized. It remains attached to receptors for longer durations, leading to persistent depolarization of receptors. Muscle membrane becomes irresponsible to further stimulus and this is known as phase I block or depolarizing block. Small contractions of the muscle fibers and fasciculations are seen in this phase.

Phase II Block

After some time, the muscle membrane becomes desensitized to the effects of neurotransmitters, this is known as phase II block or the desensitizing block. In this phase, flaccid paralysis of the muscles is seen.

Over dosage

The effects of this drug cannot be antagonized by anti choline esterases.

Ventilatory support and supportive management is required as there is no antidote.

If injections are repeated within 5-10 minutes, severe bradycardia occurs, leading to cardiac arrest. Atropine is then given in a dose of 1.5 mg to prevent cardiac arrest. Reason of bradycardia is:

Direct myocardial effects
Increased muscarinic stimulation
Increased ganglionic stimulation

Stimulates Muscarinic & Nicotinic receptors

This drug stimulates both nicotinic and muscarinic receptors;

In low doses, negative ionotropic and chronotropic effects
In high doses, positive ionotropic and chronotropic effects

Pharmacokinetics

Given by I/V route.

Has rapid onset (in one minute)

Duration of action is 5-10 minutes (short) due to degradation by enzyme psudocholine esterase, metabolized into choline and succinic acid. (Succinyl choline broken into succinomonocholine, which gives choline and succinic acid)

Certain local anesthetics like procaine are also metabolized by pseudocholine esterase, which can potentiate the effects of succinyl choline (suxamethonium) when given together.

Therapeutic Uses

For short surgical procedures (abdominal surgeries)
Bronchoscopy
Laryngeoscopy
Esophagoscopy
Can be used in electroconvulsive therapies to prevent convulsions and trauma e.g. status epilepticus
Also used in orthopedic manipulations

Adverse Effects

In patients with atypical pseudocholine esterases, suxamethonium is not metabolized, leading to prolonged respiratory paralysis and apnea. This may occur in liver disease or genetically atypical enzyme.
Can produce bradycardia if given for a prolonged period of time repeatedly.
Muscle pain may occur due to fasciculations (unsynchronized contractions of adjacent muscle fibers before paralysis)
Malignant hyperpyrexia, an idiosyncratic response. There is hyperthermia, hyertonia and hyperpyrexia along with hyperkalemia
Can lead to increased intragastric pressure (5-40 cm H2O) and can produce vomiting, aspiration pneumonia. Thus should be given on empty stomach. Following are more prone:
a. Diabetics having delayed gastric emptying
b. Trauma
c. Obesity
d. Esophageal dysfunction
Can increase intraocular pressure, due to contraction of intraocular muscles during phase I block or due to dilatation of intraocular choroidal blood vessels.
Hyperkalemia due to muscle damage, dangerous in patients predisposed to hyperkalemia like patients with wounds, trauma and peritoneal infections. It might lead to cardiac arrest.

Contraindications

Hyperkalemia
Atypical pseudocholine esterases
Liver diseases
Increased intraocular pressure as in glaucoma

Drug Interactions

Metabolized by pseudocholine esterase, all of drugs metabolized by same enzyme potentiate each other’s effects. Local anesthetics can potentiate the effects of suxamethonium e.g. Procaine or lidocaine can potentiate the effects.