20B10: Exam Report
Describe the pharmacology of suxamethonium
63% of candidates passed this question.
This was a level 1 pharmacology question, and it represents core knowledge. The mechanism of action of suxamethonium and the interactions at the neuromuscular junction as well as pharmaceutics were areas that often required further detail. Few candidates mentioned the effects of suxamethonium on the autonomic nervous system. Another common omission related to the factors that reduce plasma cholinesterase activity beyond genetic deficiency (such as liver disease, renal failure, thyrotoxicosis). Pleasingly, there was generally a good understanding of role, dosing, side effect profile, pharmacokinetics and of special situations and limitations of use pertinent to this drug.
L2i / 20B10: Describe the pharmacology of suxamethonium
Suxamethonium
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
- Author: Krisoula Zahariou