Non Depolarising NMBs

Quaternary amines
Compete with ACh at post synaptic nicotinic receptor
Do not stimulate the receptor
Bind to α subunit of receptor preventing access by ACh
Given in x2 ED95 doses

Aminosteroids

Vecuronium
Rocuronium
Pancuronium

Benzylisoquinoliniums

Atracurium
Cisatracurium
Mivacurium

Reversal times mins
Vecuronium 30
Roc 30
Panc 75
Atracurium 25
Cisatracurium 45
Miv 15

Metabolism

Vec
25% renal
Rest liver (deacetylation)
Minimally prolonged in renal failure
Significantly prolonged in hepatic failure

Roc
Hepatic
Inactive metabolites

Panc
60% renal
40% liver

Atracurium
Main is Hofmann degredation (spontaneous degredation at certain temp and pH) → laudanosine (eleptogenic)
Minor non specific esterases
Therefore drug of choice in renal and hepatic failure

Cisatracurium
Mostly Hofmann
No histamine release, more potent, slower onset (4 mins) as atracurium

Mivacurium
Metabolised by plasma cholinesterase
Therefore prolonged if abnormal enzymes (up to 8h)


Depolarising NMBs

Suxamethonium

Uses
Rapid neuromuscular blockade
Low dose for treatment of laryngospasm

Chemical
Equivalent of 2 ACh molecules stuck back to back

Mode of action
Stimulates post synaptic nicotinic receptors → depolarisation → fasciculations → remains attached to receptor for a few mins (ACh usually broken down in milliseconds) diffusing away down a concentration gradient
When attached the ion channel cannot close and the muscle becomes flaccid

Route
IV or IM
Potentiates NDMR given afterwards

Effects
CVS
Bradycardia if repeat dose
RS
Apnoea
CNS
Fasciculations then phase 1 block
Sustained but reduced tetanus – no fade or PTP
↓ but equal TOF
Potentiated by anticholinesterases (inhibit plasma cholinesterase as well as acetylcholinesterase)
If repeated admin phase 2 or dual block
↑ICP, ↑IOP
GI
↑gastric pressure
Other
↑K 0.5mmol/l
MH
Anaphylaxis (rare but more common then with any other relaxant)
Prolonged block
Muscle pains

Metabolism
Hydrolysed by plasma cholinesterase
Decreased enzyme activity
  • Pregnancy
  • Liver disease
  • Cardiac/renal failure
  • Hypoalbuminaemia
  • Burns
  • Hypothyroid
Other drugs that are metabolised by plasma cholinesterase
  • diamorphine, ester LAs, mivacurium, aspirin
Non specific esterases
  • esmolol, remi
Abnormal enzyme
  • 14 different mutations of genes controlling synthesis of plasma cholinesterase
  • Normal is EuEu (96%). Autosomal recessive
  • 1 in 25 have EuEa → slightly prolonged action
  • If one normal Eu gene won’t last longer than 30mins
  • Max is a few hours
  • Dibucaine has been superseded by direct assay of cholinesterase activity