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Succinylcholine

Anesthetics

Drug Overview

Succinylcholine (brand names Quelicin, Anectine) is a depolarizing neuromuscular blocking agent used to induce short-term paralysis during surgical procedures and rapid sequence intubation.

It is commonly used to facilitate tracheal intubation and to provide muscle relaxation during surgery or mechanical ventilation.

Succinylcholine works by mimicking acetylcholine at the neuromuscular junction, causing persistent depolarization of the motor endplate and resulting in muscle paralysis.

Relevant Genes and Their Roles

The primary gene influencing response to succinylcholine is BCHE, which encodes the plasma enzyme butyrylcholinesterase (also known as pseudocholinesterase).

Butyrylcholinesterase is responsible for hydrolyzing succinylcholine in the bloodstream. Genetic variations in BCHE can reduce or abolish this enzyme’s activity, leading to slower drug breakdown and prolonged muscle paralysis.

Impact of Genetics on Drug Response

Genetic variations in BCHE classify individuals as normal, intermediate, or poor metabolizers, which influences succinylcholine levels and the risk of extended neuromuscular blockade. Poor metabolizers have significantly reduced enzyme activity and are at high risk of prolonged paralysis, intermediate metabolizers have moderately reduced function with intermediate risk, and normal metabolizers break down the drug at expected rates. When BCHE activity is indeterminate or not available, standard dosing with careful monitoring is recommended.

Expected Clinical Effects of Genetic Variation

Ultra-rapid/Rapid Metabolizer

  • Effect: Lower than expected drug levels due to rapid hydrolysis
  • Clinical consequence: Shortened duration of neuromuscular blockade; may require additional dosing
  • Side effects: Reduced efficacy of paralysis; generally mild and managed with dose adjustment

Normal Metabolizer

  • Effect: Normal metabolism and drug levels
  • Clinical consequence: Expected onset and duration of paralysis
  • Side effects: Standard transient muscle fasciculations; mild and common

Intermediate Metabolizer

  • Effect: Higher than normal drug levels leading to prolonged blockade
  • Clinical consequence: Increased risk of extended paralysis duration
  • Side effects: Prolonged muscle weakness; moderate severity; uncommon

Poor Metabolizer

  • Effect: Much higher drug levels resulting in significantly prolonged blockade
  • Clinical consequence: High risk of long-lasting paralysis requiring extended ventilation
  • Side effects: Severe prolonged muscle paralysis; severe; rare but serious

Indeterminate/Not Available

  • Effect: Unknown
  • Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring
  • Side effects: Undetermined

Dosing Guidelines

The following dosing guidelines are based on the available guidance for succinylcholine from the FDA.

BCHE Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Intermediate Metabolizer Higher systemic concentrations and higher risk of prolonged neuromuscular blockade May administer a test dose to assess sensitivity; if proceeding, administer cautiously via slow infusion with close monitoring.
Poor Metabolizer Much higher systemic concentrations and significantly increased risk of prolonged neuromuscular blockade Avoid use of succinylcholine; select alternative agents not affected by BCHE activity.
Normal Metabolizer Normal BCHE activity and expected metabolism of succinylcholine Initiate therapy with recommended starting dose and adjust per standard clinical practice.
Indeterminate / Not available Unknown impact Initiate therapy with recommended starting dose.

Alternative Treatment Options

In individuals identified as poor metabolizers of succinylcholine, alternative non-depolarizing neuromuscular blocking agents such as rocuronium, vecuronium, or cisatracurium may be considered. These are examples from guideline recommendations and not personalized medical advice.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

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