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L13: Neuromuscular blocking drugs
i.e. muscle relaxation
25
Veterinary Medicine
Undergraduate 3
06/01/2012

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Term
Clinical indications of NMJ blockade
Definition
-relax skeletal muscles for surgical access
-facilitate control of ventilation – esp large dogs – tend to R IPPV
-opthalmic surgery – need eye in central position – otherwise can only be achieved in light or deep anaesthesia, neither of which is ideal
-assist reduction of dislocated joints and fractures? – when fresh before scar tissue formed
-decr. the amount of anaes. agent required
Term
What must be considered when using NMJ blockade?
Definition
-Facilities for endotracheal intubation and IPPV must be available
-remember no analgesia and anaesthetic effects
Term
Different sensitivities of muscles to NMJ bloackade
Definition
-diaphragm most R - intercostals - larynx - peripheral muscles most susceptible
Term
depolarising muscle relaxants
Definition
suxamethonium
Term
Suxamethonium - mode of action
Definition
-depolarising (non-competitive) muscle relaxant - a nicotinic ACH-R agonist, activates R but to a lower degree than ACh and not broken down by AChE -broken down by plasma cholinesterases, which is much slower than AChE
Term
Suxamethonium pharmacokinetics
Definition
-fast onset -initial muscle fasiculation / twitch -only one dose or get phase II block -no antagonist available -short duration - 3-5mins in cats, 20mins in dogs
Term
Suxamethonium use
Definition
-aid intubation in cats and pigg
Term
Suxamethonium CI / side effects
Definition
-may trigger maliganant hyperthermia in susceptible pig breeds
-incr. serum K+ levels
-burns - incr, the no. of R and so exaggerated response
Term
Non-depolarising (competitive) muscle relaxants drugs
Definition
-atracurium
-vecuronium
Term
Non-depolarising (competitive) muscle relaxants basic mechanisms
Definition
-compete w. ACh for post junctional binding sites -no initial muscle fasiculation -rel. slow onset (3-5 mins) -can be topped up w. 1/3 initial dose -can be antagonised
Term
Atracurium
Definition
-a non-depolarising (competitive) muscle relaxant -consists on 10 isomers, only one active - cisatracurium
Term
Atracurium pharmacokinetics
Definition
Hoffman elimination i.e. T dependent degradation in the plasma
Term
Atracurium side use
Definition
agent of choice for animals w. renal / hepatic compromise (broken down in the plasma)
Term
Atracurium side effects / CI
Definition
-histamine release therefore needs to be given slowly -breakdown product Laudanosine can cause seizures in some dogs - only at v. v. high doses so unlikely
Term
Cisatracurium
Definition
-active isomer of atracurium
-can give alone to avoid side effects of atracurium but very expensive so not realistic
Term
Vecuronium
Definition
-a non-depolarising (competitive) muscle relaxant
-steroid compound
Term
Vercuronium pharmacokinetics
Definition
-a powder which has to made up and is then stable for only 24hours
-40-50% undergoes hepatic biotransformation
Term
Vercuronium use
Definition
-not ideal if hepatic/renal compromised
-does not release histamine - cardiac stable - advanatage
Term
Signs of inadequate depth of anaesthesia when using NMJ blockade
Definition
NB: muscles relaxed so can't use many reflexes e.g. palbepral / pedal
-incr pulse rate, BP
-saliavation, lacrimation
-vasovagal response - bradycardia, hypotension, pallor
-incr. end tidal CO2 (unrelated to change in ventilation - muscles trying to work so produce CO2!)
-slight muscle twitching
-pupillary dilation
Term
Monitoring NMJ blockade
Definition
NB: animal could be very deep w. no NMJ blockade or vica versa! -use a peripheral n. stimulator over ulnar, peroneal or facial nn. - 4 electrical impulses applied to a nerve over 2 second period -asses 'train of four' - w/o blockade there would be 4 muscle twitches of equal strength -as blockade increases, the twitches dec. in no. and strength - twitch 1 may be present, 2 and 3 may be decr. and 4 may be absent -only monitors degree of NMJ blockade not anaes. depth
Term
Factors influencing NMJ blockade
Definition
-volatile agent
-hypothermia - incr. duration of blockade (esp w. atracurium - metabolism is T dependent!)
-hepatic / renal insufficiency
-electrolyte and acid base abnormalities (affect ionisation of drug)
-muscular dz. e.g. myaesthenia gravis
-aminoglycoside antibiotics (incr duration of block due to affect Ca++ post-synaptic channels)
-dose administered
Term
Signs of inadequate depth of anaesthesia when using NMJ blockade
Definition
NB: muscles relaxed so can't use many reflexes e.g. palbepral / pedal
-incr pulse rate, BP
-saliavation, lacrimation
-vasovagal response - bradycardia, hypotension, pallor
-incr. end tidal CO2 (unrelated to change in ventilation - muscles trying to work so produce CO2!)
-slight muscle twitching
-pupillary dilation
Term
Antagonism of NMJ blockade
Definition
-only possible in non-depolarising, competitive blockers and once 1 or 2 twitches return -use AChE e.g. neostigmine -ACh conc. increase and competes w. NMJ blockade
Term
Side effects / considerations when using NMJ blockade antagonists
Definition
-bradycardia (can be severe enough to cause cardiac arrest), salivation, bronchospams, diarrhoea
-administer anticholinergic drugs w. AChE e.g. atropine, glycopyrrolate (both short acting) to counter the effects of the AChE - NOT to horses
-Ventilation must be supported until spontaneous vent. commences
Term
Recent advances in NMJ blockade
Definition
-cyclodextrins - antagonise NMJ blockade - doughnut structure and encapsulates NMJ blockade drug so can't act
-New NMJ blockade drugs can be terminated by cysteine adduction
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