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
