Local anaesthetics (L13) Flashcards

1
Q

what are anaesthetics?

A

drugs which are used to prevent pain for a limited period of time for surgical or other procedures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are analgesics?

A

used to control pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

whats the difference between local and general anaesthetics?

A

local prevent localised pain or nociception and also prevent tactile sensation

general also induce loss of consciousness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what do local anaesthetics do?

A

block electrical signalling in neurones by blocking vg Na+ channels

can’t have propagation of AP

no signalling = no pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are vg ion channels composed of?

A

3 subunits:
• alpha
• beta 1
• beta 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

alpha subunit of vg ion channels

A

a single polypeptide

contains extracellular domains, 4 transmembrane domains each comprising 6 alpha-helical regions

contained voltage sensors in the hydrophobic domains that change orientation when voltage varies
• opening and closing of the pore

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

beta subunits of vg ion channels

A

they flank the alpha subunit

beta 2 is linked covalently to alpha

beta 1 is not linked

the 2 units anchor the alpha subunit into the lipid membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how do local anaesthetics interact with vg ion channels

A

thought to interact with eh alpha subunit and physically ‘plug’ the transmembrane pore

Na+ cannot rush into neurone

bindin gisten is located in the inner end of the channel - drug needs to gain access intracellularly
• unionised forms gain access through nerve sheath and axon membrane
• ionised form bind in the channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

general structure of local anaesthetics

A

aromatic group
ester or amide group
amine group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

why is the structure of local anaesthetics important?

A

basic side chain ensures molecules are poised at physiological pH

aromatic domain ensures lipid solubility

duration of action is limited by the hydrolysis of the ester/amide bond and by the lipid solubility of the agent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

whats the difference in having an ester or having an amide group?

A

esters
• metabolised in plasma by esterases
• shorter half-life

amides
• metabolised in liver by CYP 3A4, 1A2
• longer half-life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

anaesthetic action

A

anaesthetic (weak base), is injected as HCl salt in an acid solution

following injection, pH increases and drug dissociated and free base is released

lipid soluble free base enters axon where pH is lower and re-ionisation takes place

re-ionised portion enters Na+ channels and blocks them, preventing depolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

how can we manipulate local anaesthetics?

A

restrict site of action and prolong durations of action
• co-anminister adrenaline

accelerate speed of onset of anaesthetic
• using slightly alkaline solution assists absorption of anaesthetic into nerve tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

do all nerves show similar susceptibility to local anaesthetics?

A

different types of axons show different sensitively

all axons depend on vg ion channels - all affected

block conduction is smaller dimeter fibres better than larger ones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is use dependent block?

A

when the depth of block increases with an increase in action potential frequency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

unwanted side effects of local anaesthetics

A

Mose side effects occur due to escape into the systemic circulation
however, doesn’t generally get into bloodstream

CNS - confusion and agitation

cardiovascular - hypotension (low BP)

17
Q

limitations of local anaesthetics

A

not very effective in infected or inflamed tissue

they have a low pH so anaesthetic isn’t very effective

18
Q

what is the nervous system?

A

a system which allows an organism to sense information about its environment and respond rapidly and accordingly

19
Q

drug targets of chemical neurotransmission

A
  • GPCR
  • ligand gated ion channels
  • synthesis
  • release
  • uptake
20
Q

drug targets of electrical transmission

A

vg channels

21
Q

vg ion channels and toxins

A

major target for predatory animals or as a defence mechanism as well as pharmacologists

tetrodotoxin (TTX) produced by marine bacteria and by puffer fish block vg Na+ channels