Suxamethonium

Pharmaceutic

Chemical

Dicholine ester of succinic acid

Use

RSI

Presentation

Clear colourless soln, stored 4C, 100mg/2ml

Dose

1-2mg/kg TBW

Onset

<60sec

Duration

<10min

Pharmacodynamic

MoA

Agonist at nAChR

Depolarises skeletal myocyte (fasciculations)

NOT metabolized by AChE

Remains attached to nAChR

Blocks nAChR in open-inactive state

Receptor cannot repolarize

Muscle relaxation

(depolarizes before paralysis)

Relaxation requires > 20% receptor occupancy = Phase I Block

Phase II Block

Repeated or v large doses of Sux (>2mg/kg)

Prolonged binding of Sux to nAChR results in receptor desensitization

Even once drug has offset and muscle has repolarized

nAChR becomes unresponsive to Ach

last several minutes

Resembles a NDMR block

Recovery

Diffusion of SUX away from nAChR

Sux metabolized by pseudocholinesterase

Promotes concn grad for diffusion away from receptor

Prolonged Paralysis

Inherited

↓Plasma Cholinesterase activity

Acquired

Liver disease

Renal Failure, Heart Failure

Pregnancy, Elderly, Neonates (all have lower plasmacholinesterase levels)

Thyrotoxicosis

Pharmacodynamic

­↑Mg++, ↑­K (easier for sux to depolarize membrane)

Hypothermia (↓enz activity)

Drug interactions

AChE inhibitors

Mivacurium – competes for binding to pseudocholineseterase

Pharmacodynamic

MSK

Fasciulations -> Paralysis

CVS

↓HR

Resp

Apnoea

GI

­↑intragastric P,↑ ­gastric secretions

Metabolic

­↑K+

Pharmacokinetic

D

Vd, PPB unknown but rapid initial redistribution

M

Hydrolysis by plasma cholinesterase

E

2-10% excreted unchanged

t1/2b 2.7-4.6mins

Side Effects

Bradycardia

Stimulation mAChR in heart

Hypotension

Bradycardia & histamine release

Myalgia

Muscle damage due to fasciculations

↑Gastric Pressure

Abdm muscle fasciculations

LES tone is increased so no risk of regurg from this

↑K

0.5mmol/L

Increased if:

Burns – loss of PM integrity

Spinal inj, muscular dystrophies, critical illness myopathy – formation of nAChR beyond the NMJ

Renal F

Tachypylaxis

Repeated doses progress to Ph II block

Anaphylaxis

Skin rash -> cardiac arrest

Sux Apnoea

Plasma cholinesterase deficiency

MH

Trigger