Flashcards in Local anaesthetics Deck (68):
What is general anaesthesia?
Total loss of sensation.
What is local anaesthesia?
Absence of sensation in a specific part of the body.
What are the main methods of local anaesthesia?
-irreversible (ethanol, surgery, etc)
What is a local anaesthetic?
A drug that:
-REVERSIBLY prevents nerve transmission
-to REGION applied
-WITHOUT affecting consciousness
Where along an axon does a local anaesthetic work?
Anywhere along the axon.
-3 neuron chain
What is the mechanism of action of local anaesthetics?
Block voltage-gated Na channels >> no depolarisation/AP.
Where do local anaesthetics bind to Na channels?
Inside cells - has to cross membrane.
What state are local anaesthetics in when they cross the membrane and bind to Na channels?
NON-IONISED when they cross cell membrane
IONISED when they bind to Na channels
What are individual nerve fibres surrounded by?
What are nerve bundles surrounded by?
What is the outermost layer surrounding nerve fascicles called?
What are the layers surrounding nerves? (3)
ENDONEURIUM - surrounds individual nerve fibres
PERINEURIUM - surrounds nerve bundles
EPINEURIUM - outermost, surrounds fascicles
Which part of the nerve are local anaesthetics injected into?
Injected into the area around nerves, not into the nerve.
What layers must local anaesthetics pass through to enter the nerve?
-causes delayed numbness
What are the main types of local anaesthetics?
-LOCAL INFILTRATION (skin incisions)
-NERVE BLOCK (around nerve)
-EPIDURAL BLOCK (around spinal cord)
What are the ideal characteristics of local anaesthetics? (4)
-Good therapeutic index
What is therapeutic index?
-ratio of amount of therapeutic agent that causes therapeutic effect to amount that causes harm
Are local anaesthetics ever injected into nerves for quick action?
Do local anaesthetics produce reversible conduction block?
What was used as the first local anaesthetic?
-Freud noticed numbness around lips
-Koller introduced it
What is the general structure of local anaesthetics? (3)
Aromatic residue + intermediate chain + substituted amino chain.
What are the 2 types of local anaesthetics based on structure?
What are the structural differences between esters and amides?
What is the difference between the naming of ester and amide local anaesthetics?
AMIDES - 'i' before -caine
ESTERS - no 'i' before -caine
Is prilocaine an ester or an amide?
-'i' before -caine
Did Sigmund Freud first used cocaine clinically?
What are the different characteristics between local anaesthetics?
-Onset of action
-Duration of action
What is the effect if pKa (anaesthetic) = pH (body)?
Ionised and non-ionised forms of LAs are equal.
>> quicker onset
What is the effect if pKa > pH?
Ionised form > unionised form.
- delayed onset
What is the pH of the body?
-local anaesthetics with similar pKa work more effectively
What is the pH of pus, and what effect does this have?
-local anaesthetics don't work as well when inflammation is present
Which one would have a quicker onset; procaine or bupivacaine?
Procaine (pKa = 7.7).
-pKa of bupivacaine = 8.1
Do local anaesthetics with the same pKa have the same clinical onset?
-other factors involved
-e.g. diffusion rate
How does protein binding affect duration of action?
More protein binding >> longer duration of action.
Which of the following local anaesthetics has the most protein binding, and therefore the longest duration?
-lignocaine, procaine, bupivacaine
Bupivacaine - 95%
Lignocaine - 65%
Procaine - 5%
What affects the level of protein binding in local anaesthetics?
The length of the intermediate chain joining aromatic and amine groups.
What is potency?
The dose required to produce the desired effect.
What does potency depend on?
What is the effect of an increased lipid solubility?
More lipid soluble drugs penetrates the cell membrane >> smaller dose required.
What is differential block?
Nerve fibres with different functions have different sensitivities to local anaesthetics.
What does differential block depend on?
-Type of nerve fibre
-Location of nerve fibre (outside/inside mantle)
What's the effect of a larger nerve fibre?
Larger nerve fibre >> slower onset.
What order is sensory function generally lost in?
What type of sensation is lost first?
'First pain' (Ao fibres)
-then 'second pain' (C fibres)
What type of drug is often used with local anaesthetics?
What are the advantages of using vasoconstrictors with local anaesthetics? (4)
-Reduce plasma levels
-Reduced operative haemorrhage
What are the disadvantages of using vasoconstrictors with local anaesthetics?
Not used on end-vessels as >> hypoxia.
-e.g. fingers, penis, ear lobule
Give 2 examples of vasoconstrictors.
How does adrenaline cause vasoconstriction?
How much adrenaline is needed for dental LA and peripheral nerve blocks?
Dental - 1:80,000
Peripheral - 1:200,000
What is felypressin an analogue of?
What are the main differences between adrenaline and felypressin?
-Adrenaline is a more effective vasoconstrictor
-Adrenaline stimulate cardiac B1 receptors, felypressin has no effect on the heart
What affect the onset of action of local anaesthetics?
pKa of local anaesthetics.
Does adrenaline decrease the safe dose of local anaesthetics?
What are the main adverse effects of local anaesthetics? (2)
What sort of allergic response can local anaesthetics cause?
-skin rash >> shock
What type of local anaesthetic are allergic reactions more common in?
-rare with amides
Which local anaesthetic causes methaemoglobinaemia?
-due to metabolite 0-toluidine
What is the effect of O-toluidine?
Oxidises ferrous to ferric ions.
What are the main symptoms of methaemoglobinaemia?
What is the treatment of methaemoglobinaemia?
IV methylene blue.
-doesn't respond to O2
What sort of toxicity to local anaesthetics occurs first; neuro or cardiac?
-convulsions occur before cardiac arrest
How is local anaesthetic toxicity treated?
-Call for help
-Breathing (100% O2)
-Circulation (IV access)
-Consider taking blood for analysis
What drugs are used to control the seizures? (3)
What may be the initial presenting symptom of local anaesthetic toxicity?
What is the toxic does of lidocaine with and without adrenaline?
-with adrenaline; 7 mg/kg
What is the toxic does of bupivacaine/levobupivacaine with and without adrenaline?
-with adrenaline; 2 mg/kg