Muscle relaxants Flashcards
Why might we need muscle relaxation?
- to offset muscle hypertonicity with ketamine (increases muscle tone as induction agent)- can use BZPs, alpha 2s
- to relieve muscle spams (BZPs)–>pulled muscle
- to facilitate smooth induction of anaesthesia in large animals (GGE)–> centrally acting
- to improve surgical conditions
How do we produce adequate muscle relaxation for surgery
- deep general anaesthesia: induction and maintenance provide muscle relaxation- nb: profound CV depression
Local anaesthesia: can inject LA around motor nerve, muscle will relax i.e. epidural anaesthesia
Centrally acting muscle relaxants: BZPs– provide SOME muscle relaxation- centrally, not locally acting. high doses to get good muscle relaxation (side effect=respiratory depression)
Neuromuscular blocking drugs: prevent transmission at neuromuscular junction
Curare
naturally occuring muscle relaxant
not absorbed GI, don’t work orally (polar molecules)
Mechanism of action of Neuromuscular blocking drugs (NMBs/NMBDs)
target Nicotinic ACh receptor at neuromuscular junction
Signal tranmission: action potential–> calcium release pre-synaptically–>exocytosis of ACh–>activated ACh receptors open ion channels–> NA+ influx into muscle–> EPP–>AP–>contraction
ACh broken down by acetylcholinesterase– terminates action, rapidly brings ACH back into nerve terminal
NMBs: depolarizing or non-depolarizing action at post-synapstic cell. Agonists or antagonists at receptors
NB: ANTIcholinesterases block acetylcholinesterases. Can use anticholinesterase to reverse non-polarizing drugs.
NMBs work by interfering with post-synaptic action of ACh
non-depolarising: tubocurarine, gallamine, pancuronium, vercuronium, atracurium, rocuronium
depolarising: suxamethonium- not widely used in vet med
Non-depolarizing NMBs-Mechanism of action
Competitive antagonist at the nicotinic ACh receptor. Reversible! Block transmission from ACh from binding.
rigid, bulky molecules with quarternary N (polar, charged)- won’t cross cellular membranes, won’t distribute very far in body
Need to block ~80% of receptor sites- muscle tissue have receptor reserve. to block system, need to block a high proportion of receptors
Transmission is “all or nothing”- muscle either contracts or doesn’t. The varying degree of block relates to the proportion of fibres
Some may block ion channels: at higher concentrations
Reversed by anticholinesterases (if you increase the presence of ACh, can overcome block)
Muscles can still respond to K+ or direct electrical stimulation
Non-depolarizing NMBs: effects and side effects
Effects: flaccid motor paralysis- rapidly moving muscles see 1st effects
respiratory muscles last to be effected and first to recover
NB: consciousness and perception of pain are normal- no analgesic propertises. should be used as part of analgesic/anaesthetic protocol
Unwanted effects: fall in BP: ganglion block/histamine release– targeting nicotinic receptors–> N receptors at sympatetic ganglia–>fall in BP
tachycardia: muscarinic receptor block- not totally specific for nicotinic, can bind to muscarinig receptors–> decrease PS–> tachycardia
Pharmacokinetics of NMBS
mostly quaternary ammonium compounds (some steroid base)
Administered IV only- Vd ~ ECF, not highly plasma protein bound
Rate of onset and duration vary
generally metabolized by the liver or can be excreted unchanged by the kidney
Don’t cross BBB (due to physical structure) or placenta (safe to use in c-section)
Two main groups of non-depolarizing NMBs
aminosteroids (suffix “onium”): vecruonium, rocuronium, pancuronium
Benzylisoquinolines: most likely to release histamine (more of a problem in humans)
atracurium, cisatracurium, mivacurium
Vecuronium
aminosteroid non-depolarizing NMB
steroid compound
devoid of CV side-effects: most cardiostable of all muscle relaxants- no drops in CO or BP, choose for cardiac disease
excreted unchanged in bile- prolonged duration of action in severe hepatic disease (avoid if liver disease)
non-cumulative: short acting, topped up as necessary, can give as infusion
Rocuronium
aminosteroid non-depolarizing NMB
fastest onset of any non-depolarizing agent (<2 minute)
occasional tachycardia in dogs
non-cummulative
Atracurium
benzylisoquinolone
can release histamine (uncommon in animals)
Hoffmann elimination: spontaneous degradation at physiological pH and temperature. Not dependent on organ for elimination- choose this if we have patient with hepatic disease. No prolonged duration due to spontaneous breakdown in plasma.
must be stored in fridge.
Relaxants- practical use
relaxants ONLY administered IV
they will induce apnea, so patient must be mechanically ventilated
they are only administered to anaesthetized patients- can’t control ventilation in conscious patient
no anaesthetic or analgesic effects
non-depolarizing NMBs can be “topped up” or given by infusion IV for as long as required.
if you give a clinically sufficient dose, ALL muscles affected (just at different rates). Diaphgram and IC mm are most resistant and last to become affected and first to start working again. Muscles of pharyngeal area highly sensitive, eye becomes centrally fixed.
possible for patient to start breathing again as relaxant effects wears off, but not able to maintain patent airway.
Choosing a relaxant
NB: not relaxants licensed for animal use
Pre-existing pathology: cardiostability (vecuronium); renal /hepatic disease (atracurium); rapid onset (rocuronium)
Depolarizing NMBs
Mechanism of action: agonist at nicotinic ACh repector, but metabolised slowly. ACh normally rapidly cleared from synapsed. Depolarizing NMB slowly metabolised–>persistence of action–>rapid loss of muscle control–> muscle relaxes.
Flexible structure with free bond rotation- doesn’t block, but interacts with receptor as agonist.
enhanced by anticholinesterases- can’t be reversed in the same way as non-depolarizing NMBs
leads to loss of electrical excitability of muscle cells
no longer respons to K+ or electrical stimulation
Effects: initial fasciculation- twitching/trembling–> individual muscle fibres contracting
subsides as electrical excitability is lost
