Core pharmacology

Class Group

Non-Depolarizing
Isoquinolone

Legacy Cicm Level

Level 2

Introduction

Benzylisoquinolinium ester

Indications Uses

to facilitate intubation and controlled ventilation

Chemical Pharmaceutics

Bisquaternary.
10 stereoisomers.

Presentation

Clear, 10mg/mL, stored at 4 °C Racemic mixture of 10 stereoisomers: Cis-cis, cis-trans, trans-trans.

Mechanism of action

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

Onset Peak Duration

Intubate @ 90 – 120s

Duration 45mins

Adverse Effects Toxicity

HISTAMINE RELEASE
- rash, ↑HR, ↓ BP,
CAN cause bronchospasm
VAGOLYSIS
- Minimal
OTHER
- Anaphylaxis

Critical illness myopathy

Distribution

Dsn’t crss BBB
Min Crosses placenta

Protein binding

PB 15%

Volume of distribution

VD 0.15L/kg

Metabolism

40% Hofmann degradation →
laudanosine and quat.
monoacrylates
Ester hydrolysis (60%) nonspecific esterases→ quat alcohol & quat acid
Inactive metabolites

Excretion

Renal: 10-30% (laud.)
Liver: (laudanosine)

Clearance

Pl cl 7ml/kg/min

Half-life

El t1/2: 20mins

Special Points

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

Route And Dose

ED95 0.25 mg/kg
Int 0.5 mg/kg

Inf 4 – 12 mcg/kg/min