Neuromuscular Blocking Drugs Flashcards
What neurotransmitter do motor neurones use?
ACh
What is the target site of neurotransmitters from motor neurones?
Nicotinic ACh receptors (different to ganglionic) on the End Plate - usually in the middle of the fibres
What type of potential is generated in the muscle?
a Graded end-plate potential
- it depends on how much ACh is released and how many receptors are stimulated
When is an action potential generated in a muscle?
When the end-plate potential reaches a threshold. The action potential then propagates in both directions
How is ACh broken down once it has exerted its effect on the end-plate?
By Acetylcholinesterase which is bound to the basement membrane in the synaptic cleft
What are the three main neuromuscular blockers?
Tubocurarine
Atracurium
Suxamethonium
What are Diazepam and Baclofen?
Diazepam - Sapsmolytic that facilitates GABA transmission
Baclofen - GABA receptor agonist
Both potentiate the actions of GABA
What are the five sites that drugs can interact with to effect movement?
(Give the type of drug for each site)
Central processes - Spasmolytics
Conduction of AP in motor neurone - Local Anaesthetics
ACh release - Hemicholinium, Ca2+ entry blockers, Neurotoxins
Depolarisation of End-plate - Tubocurarine, Suxamethonium
Propagation of AP along fibre/muscle contraction - Spasmolytics
Where do neuromuscular blocking drugs act?
The nicotinic receptors on the motor end-plate
What type of drugs are Tubocurarine and Atracurium?
Competitive nicotinic receptor antagonists
What type of drug is Suxamethonium?
Nicotinic receptor agonist
What is the structure of Suxamethonium?
Made up of two ACh molecules that are linked together - can bind to two alpha subunits; is much more flexible and allows rotation
How does Suxamethonium cause neuromuscular blocking?
Causes extended end-plate depolarisation leading to a depolarisation block of the NMJ (phase 1)
It isn’t metabolised as rapidly as ACh so remains bound to the receptors and these will very quickly switch off
What type of paralysis does Suxamethonium cause?
Flaccid paralysis - there is no muscle tone
What are two uses of Suxamethonium?
Endotracheal intubation - relaxes the skeletal muscle of the airways
Muscle relaxant for Electroconvulsive therapy
What are three unwanted effects of Suxamethonium?
Post-op muscle pains due to initial fasciculations (fibre twitches as the drug begins to stimulate the receptors)
Hyperkalemia after soft tissue injury or burns - loss of innovating neurones leading to upregulation of receptors = deinnervation supersensitivity. Suxa will then give an exaggerated response and you will get a bigger influx of Na and efflux of K. This can lead to Ventricular arrhythmias/cardiac arrest
Raised intraocular pressure - avoid for eye injuries and glaucoma
What is the effect of Suxamethonium on the heart?
Why are the effects usually prevented?
Bradycardia due to muscarinic action on the heart
Effects generally prevented as Atropine (muscarinic antagonist) is usually given in anaesthetic pre-med
What is the route of administration for Suxamethonium and how long is its duration of paralysis?
Intravenous
5 minutes
What is the mechanism of action of Tubocurarine?
It is a competitive nicotinic ACh receptor antagonist
If 70-80% of receptors are blocked, then full relaxation of muscles is achieved as the threshold is not reached
What is the effect of Tubocurarine?
Flaccid paralysis
What is the main use of Tubocurarine?
Relaxation of the skeletal muscles during operations
This allows lower doses of GA as the role of making the muscles relax has been taken over by the Tubocurarine
It also permits artificial ventilation
How can the effects of Tubocurarine be reversed?
What drug is given with it and why?
With an anticholinesterase like Neostigmine
Atropine is also coadministered to prevent muscarinic receptor overstimulation
What is the route of administration for Tubocurarine and how long does the paralysis last?
Intravenously (does not cross BBB or placenta)
40-60 mins
What drug would you give instead of Tubocurarine in patients with impaired hepatic or renal function?
Atracurium (15 min duration)
Not affected by liver or kidney function unlike Tubocurarine
What two ways can Tubocurarine cause unwanted effects and what are they?
Ganglion Block:
- Hypotension, Tachycardia
Histamine release:
- Hypotension, bronchospasm, excessive secretions, apnoea
