Local anaesthetics Flashcards
What is the mechanism of action of local anaesthetics?
Local anaesthetics block voltage gated Na channels from inside the nerve axon.
They must first pass through the lipid membrane in their unionized form.
What affects the potency of local anaesthetics?
The lipid solubility as the more lipid soluble the more local anaesthetic available intracellularly to block the voltage gated Na channels.
The lipid solubility is expressed as the partition coefficient (the higher the number the more lipid soluble)
Which factor effects the onset of action of local anaesthetics?
The amount of the anaesthetic in its unionized form.
What determines the proportion of any drug in the ionized vs unionized form?
It is dependent on:
-Whether the drug is an acid or a base.
-The pKa value of the drug (aka the pH at which the drug is equally ionized and unionized).
-The pH of the environment
Are local anaesthetics acids or bases, and how will this affect the degree of ionisation in relation to their pKa?
Local anaesthetics are all weak bases.
Weak bases are more ionised at pH’s below their pKa value. *
*Think of the basement aka below.
How could you manipulate the speed of onset of action of local anaesthetics?
By changing the pH of the environment.
Local anaesthetics are weak bases and therefore are more ionised at pH’s below their pKa. Therefore in acidic environments they will be more ionised.
To cross the lipid membrane they need to be in their unionised form.
Therefore in acidic conditions the onset of action will be slower and in alkali conditions the onset will be quicker.
Explains why efficacy of local anaesthetic in infected tissues (acidic environment) may be reduced.
To speed the onset of action you could increase the pH level with sodium bicarbonate.
What influences the duration of action of local anaesthetic?
- Protein binding
- Rate of removal from site and subsequent metabolism. *
Addition of adrenaline 1 in 200000 to lidocaine can be used to prolong the duration of a block by causing vasoconstriction therefore reducing rate of removal.
What are the two chemical groups that local anaesthetics fall into, and what is the clinical significance?
Ester local anaesthetics and amide local anaesthetics
Esterases are present in the bloodstream as well as a variety of other tissues, ester local anaesthetics are therefore more readily broken down and have a shorter duration.
Amidases are found in the liver. Furthermore amide local anaesthetics are more highly protein bound which increases their duration.
(Think of high protein binding acting as a depot of the drug)
Give examples of amide local anaesthetics?
Lidocaine
Bupivacaine
Prilocaine
Ropivacaine
What is the safe dose limit for lidocaine?
3ml/kg without adrenaline
7ml/kg with adrenaline
Give examples of ester local anaesthetics?
Tetracaine
Cocaine
