Mechanism of action Flashcards
Why must the the LA enter in an unionised form
- Local anaesthetics are weak bases, around 5-20% with be unionised
- LA receptor is not on the external side of the cell
- LA must enter in an unionised form so once it has diffused in, then an ionised form can bind to the Na+ channel
What is the pKa
- The pH at which concentrations of ionised and unionised forms of the LA are equal
- When the pH is lower than the pKa, the ionised form of the LA predominates
Where is the binding site located
At the cytoplasmic portion of the sodium channel
What are the major determinants for the diffusion of LA into nerve fibres
- Site of administration
- Type of drug
Why must a high concentration of LA be given
Only a small fraction of LA molecules reach the target site
When do channels have less affinity for LA?
When is the exception?
In their resting state, as opposed to activated and inactivated channels
Benzocaine is the exception, which blocks the resting channel
What increases the blocking effect
Increasing the neuron firing frequency
What does the degree of block produced at a given concentration of LA depend on
Depends on the recent frequency of neuron firing
What is a tonic blockade
When there are long intervals between impulses, the level of inhibition of each impulse is the same
What is a phasic blockade
When intervals between impulses is short, the level of inhibition increases with each impulse
When increases as the concentration of LA applied to the nerve fibre increases
Threshold for excitation:
- Impulse conduction slows
- The rate of the rise of the action potential declines
- The action potential amplitude decreases
- The ability to generate an AP is abolished
What happens if the sodium current is blocked over a critical length of the nerve
Propagation of AP across the blocked area is no longer possible
