Neuromuscular Blocking Drugs Flashcards
Describe the stages of NM transmission
ACh is produced using CAT -> AP propagation -> Ca2+ influx -> ACh exocytosis -> ACh binds to receptors and Na+ influx -> ACh esterase breaks down ACh -> recycling uptake
What are the 3 most important NM blocking drugs?
Tubocurarine, atracurium, suxamethonium
Give examples of competitive (antagonists) NM blocking drugs
Tubocurarine and atracurium
Give an example of a depolarising NM blocking drugs (cause depolarising block)
Suxamethasonium
What factor means that it is possible to produce selective drugs for the somatic nervous system?
The NMJ nAChR is different in structure to the ganglionic (ANS) nAChR
What are the different subunits to the nicotinic acetylcholine recepor?
Alpha 1, Alpha 2, Beta, Delta and Gamma
What is the structure of the nicotinic acetylcholine receptor?
There is a large extracellular domain and a slightly smaller intracellular domain
What is the density of nicotinic acetylcholine receptors on the motor end plate like?
Very High
What are sites of action of skeletal muscle relaxants?
- Central processes
- Conduction of nerve AP in motor neurone
- ACh release
- Depolarisation of motor end plate - AP initiation
- Propagation of AP along muscle fibre and muscle contraction
What are examples of drugs that target the central processes of skeletal muscles?
Spasmolytics eg Diazepan and Baclofen
What are examples of drugs that target the conduction of nerve AP in motor neurones in skeletal muscles?
Local anaesthetics
What are examples of drugs that target ACh release in skeletal muscles?
HEM Ca2+ entry blockers
Icholinium
Neurotoxins
What are examples of drugs that target depolarisation of motor end plate and AP initiation
Tubocurarine
Suxamethonium
What are examples of drugs that target AP propagation along muscle fibres and muscle contraction?
Spasmolytics eg dantrolene
How do postsynaptic NM blocking drugs affect consciousness and pain sensation
These drugs do not affect consciousness or pain sensation
What must always be assisted when taking post synaptic NM blocking drugs and give examples of these drugs?
Respiration must be assisted eg taking tubocurarine, atracurium, suxamethonium or succinylcholine
What is the method of action of suxamethonium?
It causes a LONG DEPOLARISING BLOCK as it takes a long time to break down in the synaptic cleft and causes FASCICULATIONS then leading to a flaccid paralysis
What is a fasciculation?
Brief twitch of muscle fibre
How is suxamethonium administered? why is it done like this?
IV (highly charged so IV best way)
What is the duration of paralysis of suxamethonium?
Short at approx 5 mins
How is suxamethonium metabolised?
By a pseudo-cholinesterase in the liver and plasma
What are uses for suxamethonium?
Intubation to relax vocal chords and as a muscle relaxant for electroconvulsive therapy
What are unwanted effects of suxamethonium?
Post op muscle pains
Bradycardia due to direct muscarinic action to the heart
Hyperkalaemia
Increase in IOP (therefore dont give to glaucoma patients)
What is the method of action of tubocurarine?
It is a competitive nAChR antagonist that blocks 70-80% of what is necessary to cause skeletal muscle relaxation
What are the effects of tubocurarine?
Flaccid paralysis which affects the muscles in a particular order:
- Extrinsic eye muscles (double vision)
- Small muscles of the face, limbs and pharynx
- Respiratory muscles
In what order do the muscles recover from the effects of tubocurarine?
In a backwards order to how the muscles are effected so the resp muscles recover first and eye muscles recover last
What are the clinical uses of tubocurarine?
Relaxation of skeletal muscles during surgical operations
Permits artificial ventilation as it relaxes the resp muscles
How can the effects of non depolarising NM blockers be reversed?
Using anticholinesterases eg neostigmine
How is tubocurarine administered? Why is it administered this way
Via IV as highly charged
How long does the paralysis from tubocurarine last?
A long time approx 40-60 mins
How is tubocurarine removed from the body?
It is not metabolised but excreted via urine and bile
Why can atracurium be used in patients with renal or hepatic impairment and how long does it last?
It is chemically unstable and lasts 15 mins
What are the unwanted effects of tubocurarine?
Causes a ganglion block and histamine release leading to: Hypotension Tachycardia Bronchospasms Excessive secretions Apnoea
Which of the following effects would be observed with a non depolarising neuromuscular block?
- initial muscle fasciculations
- irreversible nAChR blockade
- The block would be enhanced by anticholinesterase drugs
- Flaccid paralysis
- Increased arterial pressure
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The clinical use of NM blocking drugs will must likely involve interference with which of the following physiological processes?
- kidney function
- conciousness
- body temperature regulation
- pain sensation
- respiration
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