Local Anaesthetics Flashcards
Define Local Anaesthetic.
Drugs that reversibly block neuronal conduction when applied locally
What is the rapid depolarisation stage of the action potential caused by?
Voltage-gated sodium channels
What are the three components that make up all local anaesthetics?
Aromatic region
Amide or ester link
Basic amine side-chain
What are the two types of local anaesthetics? Give an example of each.
Ester = COCAINE
Amide = LIDOCAINE
Name a local anaesthetic that doesn’t fit the structure of all other local anaesthetics.
Benzocaine – it has an alkyl group rather than the basic amine side chain
NOTE: this means that it is relatively weak but highly lipid soluble (good for surface anaesthesia)
What are the two pathways of local anaesthesia? State which one is more important.
HYDROPHILIC – most important
Hydrophobic
Describe the hydrophilic pathway.
Unionised LA from the blood crosses the connective tissue sheath and the axon membrane and gets into the axon
Within the axon it forms the cation form of the LA
This cation form then binds to the inside of the voltage-gated sodium channels (when they open) and block sodium entry
This blocks action potential conduction
What feature of local anaesthetics helps make it more selective for nociceptive neurones?
Use-dependency
They alsi target unmyelinated + small neurons.
C fibres are unmyelinated, C and Adelta fibres are also the smaller dimeter fibres hence these are targetted
Describe the hydrophobic pathway.
Some very lipophilic local anaesthetics will move into the cell membrane (in unionised form) and then drop straight into the sodium channel
It will then become the cation form in the sodium channel
And it will block sodium influx
What effect do local anaesthetics have on resting membrane potential?
No effect on resting membrane potential
Explain the effect of local anaesthetics on channel gating.
There is some suggestion that local anaesthetics bind more strongly to the sodium channels in their inactive state
Once bound to the sodium channel, it then holds it in the inactive stage for longer thus increasing the ABSOLUTE refractory period and reducing the frequency of action potentials
Explain the effect of local anaesthetics on surface tension.
They lodge into the plasma membrane and reduce surface tension of the membrane
This leads to non-selective expansion of the lipid membrane and leads to non-specific inhibition of ion channels
Describe the selectivity of local anaesthetics.
Preference for small diameter axons (e.g. nociception neurones)
Tend to block non-myelinated axons
Describe the pKa of all local anaesthetics.
8-9
All local anaesthetics are WEAK BASES
Explain why it is difficult to anaesthetic infected tissue.
Infected tissue is ACIDIC
So there will be less anaesthetic that is unionised
What are the 6 methods of administration of local anaesthetics?
Surface anaesthesia - eg eye drops
Infiltration anaesthesia
Intravenous regional anaesthesia
Nerve block anaesthesia
Spinal anaesthesia
Epidural anaesthesia
What are the consequences of using high doses in local anaesthesia?
It can cause systemic toxicity
What is infiltration anaesthesia?
Injection of anaesthetic directly into the tissue near the sensory nerve terminals
You would inject at the site of damage eg next to the place you make the incision as a surgeon
It is used for minor surgery
What is often coadministered with infiltration anaesthesia and what are the benefits of this?
Adrenaline – this causes vasoconstriction and increases the duration of action of the anaesthetic meaning that a lower dose can be used
It also slows bleeding at the site of injection and reduces the amount of local anaesthetic going into the systemic circulation
NOTE: felypressin (V1 agonist) can also be used
What is intravenous regional anaesthesia and how can this cause systemic toxicity?
Pressure cuff is used to cut off the venous drainage
Anaesthetic is administered intravenously
Removing the pressure cuff too early can lead to a bolus of anaesthetic entering the systemic circulation - leave cuff for at least 20 minutes
What is nerve block anaesthesia? Describe the dosage and onset.
Inject anaesthetic close to the nerve trunks
this is different to infiltration anaesthesia, in this method, you normally inject and block a BUNDLE of nerves (definition of nerve trunks) eg the brachial plexus. For infiltration anaesthesia, you inject it near the site of injury.
Low doses and slow onset
What is coadministered with nerve block anaesthesia?
A vasoconstrictor e.g. adrenaline
What is another name given to spinal anaesthesia?
Intrathecal
Where is the anaesthetic inserted in spinal anaesthesia?
Into the subarchnoid space (into the CSF) through the dura
