Pharm 10 - NMJ blocking drugs Flashcards
Somatic motor nervous system uses which neurotransmitter?
ACh. Only a single axon
What enzyme is used for ACh synthesis?
CAT (cholinoacetyl transferase)
Muscle type NAChR are different to ganglionic NAChR?
True
ACh binds to the alpha subunits of the NAChR. Typically how many ACh must bind to the NAChR for it to open?
2
Baclofen is a spasmolytic. It is a —— agonist
GABA
What do local anaesthetics act on?
VGSC
Dantrolene is a spasmolytic. Where does it work and what is its mode of action?
Inhibits release of Ca from Sarcoplasmic reticulum stores - less powerful muscle contraction
What are the sites of action of drug action?
- Central processes
- Conduction of AP along motor neurone
- ACh release
- Depolarisation of motor end plate - AP initiation
- Propagation of AP along muscle fibre + muscle contraction
What drugs can be used to target central processes?
Spasmolytics - e.g. diazepam or Baclofen
What drugs can be used to target the conduction of AP along motor neurone?
Local anaesthetics
What drugs can be used to target ACh release?
- Ca entry blockers
- Neurotoxins (e.g. botulinum)
- Hemicholinium
What drugs can be used to target depolarisation of motor end plate ?
- Tubocurarine
2. Suxamethonium
What drugs can be used to inhibit propagation of the AP along muscle fibre?
Certain spasmolytics e.g. Dantrolene
Do neuromuscular blocking drugs work presynaptically or postsynaptically?
Postsynaptically
What are the 2 classes of neuromuscular blocking drug that work postsynaptically?
- Non-depolarising (competitive antagonists)
2. Depolarising (agonists)
Give an example of a non-depolarising NM blocking drug?
Tubocurarine
Atracurium
Give an example of a depolarising NM blocking drug
Suxamethonium
Do NM blocking drugs affect consciousness or pain sensation?
No
What must always be assisted when giving NM blocking drugs in surgery?
Respiration
What is the mode of action of suxamethonium?
Excessively stimulates NAchR on end plate - causing extended depolarisation. Suxamethonium takes 5/6 minutes to leave the synaptic cleft
This causes “depolarisation block” (aka Phase 1 block)
What other drug can also cause depolarising block?
Ecothiopate
What can happen in the first few minutes after administering suxamethonium?
Fasciculations - muscle twitches
Flaccid paralysis may follow - loss of tone in SkM
How is suxamethonium administered?
Intravenously
What is the duration of paralysis with suxamethonium?
5 minutes (SHORT)
What is suxamethonium metabolised by?
Pseudo-cholinesterase
Name 2 uses of suxamethonium
- Endotracheal intubation
2. Muscle relaxant for ECT
What are some unwanted effects of suxamethonium?
- Post-op muscle pains
- Bradycardia due to direct muscarinic action on the heart (M2 receptors) but this is usually solved by coadministration of atropine
- Hyperkalaemia - e.g. giving patients with soft tissue damage/burns patients is very dangerous - causes greater sodium influx and greater K efflux
- Increased intraocular pressure - avoid for patients with eye injuries or glaucoma
Why is it dangerous to give burns patients/soft tissue damage patients suxamethonium?
De-innervation up regulation of NAChR on SkM
What can hyperkalaemia cause (in worst case scenarios)?
Ventricular arrhythmias and cardiac arrest
What is a naturally occurring 4 Ammonium compound (alkaloid) found in S.American plants?
Tubocurarine
What is the mode of action of tubocurarine?
Competitive NAChR antagonist - competes with endogenous ACh
What % block is needed from tubocurarine to prevent the End plate potential firing an AP?
70-80% BLOCK
What are the effects of tubocurarine?
Flaccid paralysis
- Initially, extrinsic eye muscles relax (double vision)
- Then small muscles of face, limbs, pharynx
- Then, respiratory muscles
What is tubocurarine used for?
- SkM relaxation for surgery (means less General anaesthetic is needed)
- Relaxes respiratory muscles, allows artificial ventilation
What can non-depolarising blockers be reversed by?
Anticholinesterases (e.g. Neostigmine (+ Atropine))
How is tubocurarine given?
IV
Tubocurarine is not very lipid soluble so it doesn’t cross which 2 things?
BBB or placenta
What is the duration of paralysis with tubocurarine?
1-2 hours
Is tubocurarine metabolised?
No, it is excreted (70% urine, 30% bile)
If there are renal/hepatic problems in the patient, you don’t give tubocurarine. What do you give instead?
Atracurium (15 mins DOA) - DOA not determined by liver or kidney function.
What are the unwanted effects of giving tubocurarine?
- Ganglion block and histamine release
- Hypotension due to Ganglion block (TPR decrease) and histamine release (H1 receptor causing vasodilation)
- Tachycardia - reflex tachycardia or blockade of vagal ganglia
- Bronchospasm and excessive secretions (histamine release)
- Apnoea (always assist respiration)
What can basic drugs do to mast cells?
Cause them to release histamines
