Local Anaesthetics

Question 1

Describe the importance of structures of local anaesthetics with examples?

Answer 1

They have an aromatic group at one end with a amine group at the other that can be either a tertiary or secondary amine. They are then joined in the middle by either an ester or an amide bond - this is important in their deactivation as an ester bond is more easily broken down that the amide bond by plasma esterases. Also amide linked local anaesthetics are more likely to cause an allergic reaction. Lignocaine is a local anaesthetic that has an amide link with a teriaty amine and procaine has an ester link with a teriaty amine.

Question 2

What are the effects of local anaesthetics?

Answer 2

1. Depression of local sensory nerves which lead to the inhibition of pain so can be used in dental surgery
2. Due to blocking conduction in nerve fibres it can also block conduction in cardiac fibres which can lead ro a decreased cardaction output but this can have beneficial effects e.g. lignocaine is an antidystrhymic
3. Also have some effect on smooth muscle leading to unwante vasodilation.

Question 3

What kind of fibres are more sensitive to local anaesthetics?

Answer 3

1. Unmylinated > myelinated
2. Small > short
3. Pain > temp > touch > pressure

Question 4

How are local anaesthetics administed?

Answer 4

Topically, infiltration and regionally

Question 5

What is the mechanism of action by which local anaesthetics work?

Answer 5

They block voltage dependent sodium channels which leads to a reduction in the depolarisation of the nerves and causes APS to stop firing and therefore produces their effects. Only the ionised form can bind and block the receptor and it does this best when the receptor is in its inactive state or is open (so its use dependent). The LAis a weak base so exists in charged and undercharged form (in normmal ph enviroments 7 the overal ratio is 1 uncharge for every 10 charged (as determined by the henderson hasslelbach equation when the pka of the local anaesthetics is between 8 and 9). The unc. The local anaesthetic can eitheget into the channel as the ionised form when it is is open or it diffuses through the membrane as the uncharged form where it becomes ionised and can then access the channel from there. The uncharge from can also access the site directly fro the membrane where it can be ionised.
The voltage dependent sodium channel is composed of 4 domains each with 6 transmembrane helicies. The voltage sensor is found in the4th segment - the change if voltage produces a conformational change which is passed on the the segments 2s which line the pore causing a conformational change and the opening of the pore. There is then a inker between domains 3 and 4 which acts as a gate for the channel. local anaesthetics bind to segment 6 in domain 4.

Question 6

Bupiracaine

Answer 6

Longer lasting LA but more cardiotoxic

Question 7

Benxocaine

Answer 7

Used in throat losanges

Question 8

Articaine

Answer 8

Most favoured in dental surgery - has an amide linker