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