CPTP 3.22 - Local Anaesthetics Flashcards
Name the two fibre types that transmit painful stimuli signals to the brain?
A-delta
C-fibre
Describe the three main states that neuronal membranes can be found in?
- Resting = Impermeable to Na+ (espore region positive)
- Open = Na+ travels down concentration gradient
- Inactive = AFTER Na+ influx linker region swings around and blocks the channel physically
Where do local anaesthetics bind?
To the INTRACELLULAR side of Na+ channel
Describe local anaesthetics mechanism of action?
Reversible block of nerve conduction
Bind to intracellular side of Na+ channel and inhibit the influx of Na+ and therefore prevent depolarisation - preventing AP and prevent pain transmission
In which conformation of Na+ channels do local anaesthetics bind?
Inactive channel conformations
DON’T bind to resting conformations
Name the two chemical structures that differentiate local anaesthetic drugs?
- Aromatic group = influences hydrophobicity
2. Liner region = (Lidocaine = amide group)//ester group
How are the two linker region groups metabolised?
Ester groups (procaine) = rapidly by cholinesterase (mins) Amide groups (lidocaine) = slow in the liver
In terms of the aromatic group - how does hydrophobicity increase and why is this important?
Adding functional groups (NH2) = Increases
Poor hydrophobicity = unable to cross lipid by-layer to target the intracellular site
Extreme hydrophobicity = drug trapped inside the lipid by-layer
Describe the binding site of the local anaesthetic itself?
Hydrophobic - the more hydrophobic it is, the more tightly the drug will bind to the target site = Increased potency of the drug (trade-off with diffusion)
In terms of amine groups - describe local anaesthetics?
ALL local anaesthetics are weak BASES (proton acceptors) - the amine group is either ionised (protonated with a + charge) or UN-ionised in its normal base format
When is 50% of the local anaesthetic ionised and 50% unionised?
When the pka of the local anaesthetic = the pH of the solution
What happens to the local anaesthetic as the pH of the solution decreases?
More becomes ionised
In a set solution (pH=7.4) as the pka of the local anaesthetic increases describe what happens?
As the pka of the drug increases within a set solution MORE of the local anaesthetic is IONISED = higher ionisation with increased pka
How do local anaesthetics cross the lipid by-layer?
ONLY UN-ionised forms of local anaesthetics cross the hydrophobic lipid by-layer via passive diffusion
Once intracellular the base re-equilibrates into ionised and un-ionised forms
Which forms of local anaesthetic bind to the intracellular target site?
ONLY ionised (charged) form
Finish the sentence - ‘The lower the pka of a local anaesthetic…’?
…The greater the UN-ionised fraction = the greater/quicker the onset of action as it is able to pass through the by-lipid membrane faster
Finish the sentence - ‘The greater the hydrophobicity of a local anaesthetic…’?
The greater the potency = binds more strongly to the active site of the intracellular Na+ channel
The longer the duration of action
Why don’t local anaesthetics work in inflamed tissues?
In inflamed tissues there is acidosis = decreased pH = this increases the IONISED fraction of the drug and therefore less of it is able to cross the lipid by-layer (only un-ionised can cross)
Why are C-fibres most readily blocked by action with local anaesthetics?
Small diameter
NO myelination = smaller diffusion pathway
Finish the sentence - ‘Increasing the alkalinity of a solution of a local anaesthetic…’?
Increases its speed of action = More UN-ionised and can pass through the bi-lipid membrane
What type of local anaesthetic is used commonly with the brachial plexus?
Peripheral nerve block anaesthesia
What is critical regarding central nerve block anaesthesia?
Local anaesthetic injected MUST be below L2
