Neuromuscular blocking drugs Flashcards
Where do the cell bodies of alpha motor neurons sit?
ventral horn of vertebrae
neuromuscular synaptic terminal diagram.
6 stages.
What kind of receptors are found at the neuromuscular junction?
nicotinic type 1 (ion channel) ACh receptors.
(2 alpha subunits)
What is the relevance of nicotinic receptors at the neuromuscular junction being different to ganglionic nicotinic receptors
Neuromuscular specific drugs can be developed.
How many ACh molcules are needed to bind to nAChR to stimulate a response? Which subunits do they bind to?
2, to the alpha subunits.
(NB other subunits are beta, delta and gamma)
Name a drug type that acts on the central processes (generation of APs in the spinal cord) of the SNS. Give two examples.
spasmolytics.
diazepam, baclofen.
What drug types target conduction of nerve AP in the motor neurone?
local anaesthetics.
What types of drugs effect ACh release from the presynaptic neurone? Give an example.
Ca2+ entry blockers
neurotoxins - botulinum toxin.
hemicholinium (what is this)
Name some drugs that effect the depolarisation of the motor end plate, inhibiting AP initiation.
tubocurarine
suxamethonium
What category of drug effects propagation of AP along muscle fibre and so muscle contraction? GIve an example.
Spasmolytics - dantrolene.
What are the two classes of neuromuscular blockers? Give some examples.
- non-depolarising (competitive antagonists) - tubocurarine, atracurium.
- depolarising (agonists) - sexamethonium.
What effects do neuromuscular blockers have on consciousness, pain sensation and respiration?
consciousness - no effect.
pain sensation - no effect
assist respiration.
Explain the mechanism of action of suxamethonium.
It produces an extended end-plate depolarisation –> depolarisation block.
i.e. receptor overstimulated and then response shuts down.
What is the physiological response to suxamethonium.
fasciculations –> flaccid paralysis
How is suxamethonium administered?
I.V.
What is suxamethonium’s duration of effect?
approx. 5 mins.
How is suxamethonium metabolised?
by pseudocholinesterase in liver and plasma
What are the two main uses of suxamethinium?
- endotracheal intubation
- muscle relaxant for Electro convulsive therapy.
Outline the unwanted effects of suxamethonium.
post operative muscle pains.
bradycardia - counteracted by simultaneous atropine administration.
hyperkalaemia - in patients with soft tissue injury/burns (due to increased nicotinic receptors to amplify response to damaged area). This can cause ventricular arrhythmias/cardiac effects.
increased intraocular pressure - avoid administration for eye injury/glaucoma patients.
Outline the mechanism of action of tubocurarine (non-depolarising blocker)
competitive nAChR antagonist.
70-80% block necessary for effect.
What is the effect of tubocurarine? What is the order of onset?
flaccid paralysis.
extrinsic eye muscles –> small muscles of face, limbs, pharynx, respiratory muscles.
Recover in opposite order.
What are the uses of tubocurarine?
relaxation of skeletal muscles during surgical operations (less anaesthetic needed)
Permit artificial ventilation.
How can the actions of non-depolaring blockers be reversed?
anticholinesterases
e.g. neostigmine + atropine.
How is tubocurarine administered?
I.V.
What is the duration of effect of tubocurarine?
1-2 hours (relatively long)
(atracurium = 15 mins)
How is tubocurarine excreted? What must be considered when administering it?
not metabolised - excreted in urine (70%) and bile (30%)
dangerous if patient has impaired renal/hepatic function - atracurium used instead.
What barriers is tubocurarine unable to cross?
BBB and placenta
Outline potential unwanted effects of tubocurarine.
Ganglionic blockade and histamine release cause side effects -
hypotension (ganglion block - TPR reduces, histamine - vasodilation)
tachycardia (can lead to arrhythmias) - due to compensation for hypotension and blockade of vagal ganglia.
bronchospasm, excess bronchial/salivary secretions (due to histamine)
apnoea.
