Local Anaesthetics Flashcards
What is a local anaesthetic?
a local, reversible loss of sensation without loss of consciousness
what is LA mechanism of action
By blocking nerve conduction:
Small diameter nerve fibres are blocked more readily than large fibres.
Nocicptive (Pain fibres) impulses are carried by Aδ and C fibres (small)
The LA affects these small fibres at lower concentrations than larger fibres.
How do LA block nerve conduction
LA block Na+ channels form opening
LA enchance Na+ inactivation
What is the site of LA binding on the Na channel
The Na channel has 4 subunits each have 6 transmembrane domains
Tyrosine and Phenylalanine → interacts with LA hydrophobic γ
Process of LA interaction with phenylalanine
Drug binds to protein and alters the shape of phenylalanine via the benzyl ring. LA gives phenylalanine a positive charge Result: 1. Blockage of pore 2. Enhance inactivation
Drugs that have Local anaesthetic properties at high concentrations
- Morphine
2. Propranolol
What two forms do local anesthetics come in
charged
uncharged
What is the uncharged LA form important for
- Penetration of neural sheath (rate of onset of action).
2. Crossing the plasma membrane (access to site of action).
What is the charged LA form important for
Interacting with the Na+ channel.
What determines the percrntage of LA molecules that are ionised?
pH
pKa of the local anaesthetic (most are weak bases with a pKa in the range of 8-9)
If the pKa for Local anaesthetics is 8-9 at physiological pH of 7.4 what oercentage of LA molecules are ionised?
[LA] = 20% [LAH+] = 80%
What happens to the percentage of ionised LA as the pH drops in inflammed tissue where the pH is more acidic
The amount of ionised LA increases
Give 2 examples of atypical local anaesthetics
Benzocaine
QX-314
What is the mechanism of action of Benzocaine
Ester group, no amine group therefore unprotected (0%) ionised) works via hydrophobic pathway only
no use dependance i.e. the more often a neuron fires the greater the degree of block
What is the mechanism of action of QX-314
Permanently charged – 100% ionised.
Blocks Na channels only if introduced into cells (experimental tool).
• Cannot cross membranes.
• No therapeutic use
