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