Core pharmacology

Class Group

Depolarizing

Legacy Cicm Level

Level 1

Introduction

Dicholine ester of succinic acid

Indications Uses

1. Where ever rapid and profound muscle relaxation is required e.g. endotracheal intubation
2. For modification of fits following ECT

Chemical Pharmaceutics

Bisquaternary 2 Molecules of ACh joined by acetate methyl groups

Presentation

Clear aqueous solution, 50mg/mL suxamethonium chloride Stored at 4°C

Mechanism of action

PHASE I (depolarising) block mechanism: 2 molecules of sux binds the 2 alpha subunits of nAChR
→ activation and channel opening  depolarisation → sux is not metabolised by NMJ AChE → remains bound to nAChR → nAChR remains open & in inactive state  forms small zone of depolarisation/inactivation around synapse → blocks further depolarisation → muscle relaxation
(~ 20% post-synaptic nAChR occupancy required to achieve depolarising block)

Sux exerts pre-junctional action → retrograde conduction up motor neuron  triggers
axon to depolarise entire motor unit → fasciculation observed prior to onset of
depolarising block

PHASE II (desensitisation) block mechanism: exact mechanism uncertain.
After sux has been present for a period of time → motor end plates loses sensitivity to
ACh/sux → depolarisation cannot occur
Desensitisation continues (for several minutes) even after drug is no longer present

Onset Peak Duration

Onset IV 30 ~ 60s
IM 60 ~ 120s
Duration 5mins

Adverse Effects Toxicity

HISTAMINE RELEASE
- rash, ↑HR, ↓ BP
(NOT bronchospasm)
EFFECT ON ANS
↓ HR paeds (mAChR) (agonist at both sym/para ganglia, but kids ↑vagal tone)
OTHER
- Anaphylaxis Risk 3xND-NMB
- Malignant hyperthermia
- Myalgia (fasciculn)
- ↑ [K+] by 0.5 mmol/L
- ↑ICP ↑intraocular pressure
- Phase I + II blocks
- Sux apnea w BChEmutations
- ↑Intragastric pressure

Distribution

Highly ionised & water soluble 
Limited lipid solubility

Protein binding

Protein bound to unknown extent

Metabolism

Rapid hydrolysis by plasma
Butyrylcholinesterase.
Sux→succinylmonocholine →succinic acid + choline.
(Inactive)

Approx 10% of IV dose reaches NMJ

Excretion

Renal: <2%
Liver: nil

Clearance

Pl clearance: 3ml/kg/min

Half-life

El t1/2: 90mins

Special Points

Contraindications:
- Hyperkalaemia
- Neuromuscular diseases
- Denervation (after 2 days)
- Immobilization (after 3 days)
- Burns (after 2 days)
- Chronic NMB use (>3 days)
- Sepsis/SIRS (after 3 days)
- MH risk
- Allergy
- Homozygous for atypical plasma cholinesterase (1/3200 incidence; block prolonged by hours)

Route And Dose

ED95 0.3 – 0.6 mg/kg
RSI IV 1 mg/kg IV
IM 2 mg/kg
Infusion-