Local Anaesthetics Flashcards
When are local anaesthetics used?
When loss of consciousness is neither necessary or desirable
Post-operative analgesia
For major surgery, with sedation
Why are local anaesthetics used as an adjunct to surgery?
To avoid high-dose general anaesthetics
Structure of local anaesthetics:
Aromatic region
Basic amine-side chain
What bond is present in local anaesthetics?
Ester or amide bond
Difference between ester and amide local anaesthetics?
Esters are more unstable + can be metabolised into compounds associated with allergic reactions
Amides are more commonly used
Why are amide local anaesthetics more commonly used?
As more stable and extend duration of action
How do local anaesthetics work?
Reversibly block voltage-gated Na+ channels
What happens when local anaesthetics block channels?
Excitable membranes stabilise
Prevent membranes from being depolarised
Structure of peripheral nerve:
Consists of fibres of different function, diameter and insulation
What can peripheral nerves be blocked by?
Local anaesthetics but at different rates
Order of loss of function by local anaesthetics:
Pain
Temperature
Proprioception
Skeletal muscle tone
What does the probability that a local anaesthetic will block an impulse rely on?
Diameter of fibre
Myelination status
Length of nerve exposed to drug
Length of time exposed to drug
Concentration of drug
What size diameter of fibre are more easily blocked?
Smaller nerve fibres blocked more easily as smaller SA and lower number of channels
What amount of myelination makes a fibre more easily to block?
Myelinated fibres are blocked more easily than unmyelinated
Only need to block channels at nodes of Ranvier
Are local anaesthetics acids or bases?
Weak bases
In what conditions can local anaesthetics exist?
As neutral or protonated (become charged)
What are local anaesthetics dependent on?
pH
WHen can local anaesthetics block channels?
When they are ionised via intracellular binding site
When do local anaesthetics cross membrane?
When unionised
They can’t pass through membrane when ionised
What is pKa?
The pH at which 50% of drug is ionised
What do most local anaesthetics have pKa values between?
8 and 9
Ratio of unionised local anaesthetic :
1:1 between extracellular fluid and cytoplasm of axon
Unionised local anaesthetic can cross membranes
What types of channels do local anaesthetics bind to?
Open or inactive channels
What are many local anaesthetics related to?
Frequency of neuronal firing
