Suxamethonium Flashcards
What is the structure of Sux?
2 molecules of ACh joined back to back through their acetyl groups.
C14H30N2O4+2
Presentation and uses of sux
Colourless solution containing 50 mg.ml-1
Store at 4 degrees
Used for rapid muscle relaxation.
What is the mechanism of action of sux?
Mimics ACh by binding to nicotinic ACh receptors and causing membrane depolarisation.
Action longer than ACh as its hydrolysing enzyme is not present at the NMJ (plasma or pseudo-cholinesterase).
Persistent depolarisation renders the voltage sensitive Na+ channels within 1-2mm inactive. Prevents further APs.
Initially a phase 1 block. Phase 2 if further doses given.
Characteristics of a phase 1 block from Sux (partial depolarising)
Reduced single twitch.
TOF T4:T1 >0.7
1Hz stimulus sustained
No post tetanic potentiation
Effect of anticholinesterases: block augmented
Partial non-depolarising or phase II block characteristics
Single twitch reduced.
TOF ratio T4:T1 <0.7
1Hz stimulus: fade
Post tetanic potentiation
Effect of anticholinesterases: block antagonized
Kinetics of sux
Rapidly hydrolysed by plasma or pseudo cholinesterase (an enzyme of the liver or plasma- none being present at the NMJ).
- only 20% of original dose reaches the NMJ
- rate of hydrolysis is therefore critical in determining duration
Hydrolysed to choline and succinylmonocholine (weakly active)
- metabolised further by plasma cholinesterase to succinic acid and choline
Because metabolism is rapid, less than 10% excreted in the urine
Arrhythmias associated with sux
Sinus or nodal bradycardia and ventricular arrhythmias
- stimulation of the muscarinic receptors in the sinus node
- brady often more severe after a 2nd dose
- more pronounced in kids
Hyperkalaemia
Normal to have a 0.5 rise in K+ level.
- depolarization involves K+ efflux into extracellular fluid
Patients with burns >10% and neuromuscular disorders are susceptible to a sudden release of K+
- burns 24hrs-18 months
- extra junctional ACh receptors (fetal y subunit instead of E) proliferate and cause a larger K+ efflux
- paraplegia, progressive muscle disease or trauma induced mobility also at risk
- paraplegia = first 6 months but continues in those with progressive diseases
- renal failure advised to avoid
Myalgia
Muscle pain most common in young females mobilising rapidly in the post op period.
Pre treatment with lidocaine or NDMR (gallamine/ roc)
Intra-occular pressure and sux
Raised by about 10mmHg for a matter of minutes (normal is 10-15) and is significant with globe perforation. Contraction of extra occular eye muscles and dilation of choroidal blood vessels.
Concurrent thiopental will offset this rise
Sux effect of intragastric pressure
Rises by 10cmH2O but as the lower oesophageal sphincter tone increase simultaneously there is no increased risk of reflux
Other effects of sux
Anaphylaxis (majority)
Malignant hyperthermia
Prolonged neuromuscular block
What causes sux apnoea?
Reduction of plasma cholinesterase activity.
- genetic variable (single amino acid substitutions)
- acquired
Genetics of sux apnoea
4 alleles- usual (normal), atypical (dibucaine-resistant), silent (absent) and fluoride-resistant have been identified at a single locus of Chr 3 and make up the 10 genotypes.
96% homozygous for normal Eu gene.
4% heterozygotes resulting in mildly long block to 10mins and small amount of a few hours.
Reversed by FFP (source of plasma cholinesterase) or I&V and sedate.
What is dibucaine?
An amide LA that inhibits normal plasma cholinesterase. It inhibits the variant forms of plasma cholinesterase less effectively. AT a conc of 10-5 mol.l-1, dibucaine inhibits Eu:Eu by 80% but the Ea:Ea by 20%.
Percentage is known as the dibucaine number (smaller the %, the longer the duration of the block). Ea:Ea, Es:Ea and Es:Es as longest. Ef:Ef rarest. Percentages from 20-80.
