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

ND-NMB acts as competitive antagonist →
competes with ACh for nAChR binding → blocks cholinergic transmission → muscle
relaxation (> 70% post-synaptic nAChR occupancy required to result in block)
ND-NMB also inhibits pre-synaptic ACh receptors →prevents enhancement of ACh
release → fade with repeated stimulation

Highly ionised & water soluble 
Limited lipid solubility

Doesn’t cross BBB

Protein bound to unknown extent

PB 10%

VD 0.2L/kg

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

Approx 10% of IV dose reaches NMJ

<5% Metabolism Hep

Renal: <2%
Liver: nil

Renal: 30-40%
Liver: 60%

Pl clearance: 3ml/kg/min

Pl cl: 3ml/kg/min

El t1/2: 90mins

El t1/2: 90mins

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

HISTAMINE RELEASE
- None
EFFECT ON ANS
- Can be vagolytic (↑HR)
OTHER
- Anaphylaxis
- Pain on injection

Bisquaternary 2 Molecules of ACh joined by acetate methyl groups

Monoquaternary

Depolarizing

Non-Depolarizing
Aminosteroid

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

1. to facilitate tracheal intubation during routine and modified rapid
sequence induction
2. for controlled ventilation.

Dicholine ester of succinic acid

Aminosteroid

Level 1

Level 1

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

Int @ 100 – 120s
RSI @ 60s
Duration 35mins

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

Clear, colourless solution, 10mg/mL rocuronium bromide

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

ED95 0.3 mg/kg
Int 0.6 mg/kg
RSI 0.9 ~ 1.2 mg/kg
Inf 9 – 12 mcg/kg/min

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)

Duration prolonged by:
- ↓K ↓Ca ↑Mg
- ↑pH ↑PaCO2
- ↓temp ↓protein Dehydration

Reversible with sugammadex