Local Anaesthetics Flashcards
What is the definition of an anaesthetic drug?
A drug that induces partial or total loss of sensation
What are the 2 main types of anaesthesia?
General anaesthesia:
- this involves total loss of sensation
Local anaesthesia:
- this involves partial loss of sensation
What are the 3 different types of local anaesthesia?
Regional anaesthesia:
- involves the loss of sensation to a region or part of the body
Local infiltration:
- Involves infiltration into cuts or skin incisions
- it is more confined to the area around the wound
Topical anaesthesia:
- this involves eye drops or topical skin creams
- it does NOT involve a needle
What are the 2 different methods of local anaesthesia?
Non-pharmacological:
- cold
- pressure
- hypoxia
Pharmacological:
- reversible - local anaesthetics
- irreversible - phenol, ethanol, radiofrequency, surgery
- involves complete destruction of the nerve carrying sensation from an area to the brain
What are the fundamental characteristics of a local anaesthetic agent?
It is a drug which:
- Reversibly prevents transmission of a nerve impulse
- In the region to which it is applied
- Without affecting consciousness
What are the different ways in which local anaesthetics can be administered?
- Can be applied topically - e.g. eye drops, on mouth ulcers or skin
- local infiltration around the skin edges of a wound
- nerve block
- epidural or spinal block
Which 2 major systems are affected in local anaesthetic toxicity?
What symptoms may result?
If you give someone too much local anaesthetic, it will work on the brain and the specialised conduction system within the heart
this results in neurological and cardiovascular symptoms
What are the 3 layers of a nerve?
Where does the local anaesthetic work?
The nerve is surrounded by the epineurium
Individual nerve bundles are surrounded by the perineurium
An individual nerve fibre is surrounded by the endoneurium
the LA is injected into the epineurium and takes time to diffuse into the nerve fibre
Why are local anaesthetics sometimes called “blocks”?
What is their general mechanism of action?
They block voltage gated sodium channels along the axon
this means that action potentials cannot be generated and passed on
they work on different domains of the sodium channel and prevent Na+ ions from moving into the cell
What are the characteristics of an ideal local anaesthetic?
- Reversible
- quick onset
- suitable duration
- no local irritation on repeated application
- no side effects
- no potential to induce allergy
- applicable by all routes
- cheap, stable and soluble
From which aspect do local anaesthetics block sodium channels?
What type of block does this provide?
LAs work by blocking sodium channel conduction
they block sodium channels from the inside
they provide reversible conduction block
What are the main local anaesthetic agents?
- Procaine
- Lidocaine
- Prilocaine
- Mepivacaine
- Bupivacaine
- Levo bupivacaine
- Ropivacaine
- Articaine
What is the structure of a local anaesthetic like?
All LAs have 2 components connected with an intermediate chain
they have a lipophilic part - an unsaturated benzene ring
and a hydrophilic part - tertiary amine
What structural component determines which type of local anaesthetic it is?
The link between the intermediate chain and the benzene ring determines the type of LA
it is either ester or amide
What do the names of all LAs end in?
How can you tell if they are ester or amide?
“Caine”
If there is an i before the Caine, they are amides
if there is NOT an i before the Caine, they are esters
What are examples of ester local anaesthetics?
- Benzocaine
- chloroprocaine
- cocaine
- procaine
- tetracaine
What are examples of amide local anaesthetics?
- Bupivacaine
- etidocaine
- levobupivacaine
- lidocaine
- mepivacaine
- prilocaine
- ropivacaine
What characteristic of local anaesthetics determines their onset of action?
The pKa value
LAs can exist in the ionised or unionised form
in order to get into the cell, they have to be in the unionised form
once they are within the cell, they have to become ionised in order to bind to the channel
What does the pKa value of a local anaesthetic tell you?
The pKa value shows that ionised and non-ionised forms of local anaesthetics are equal
if pKa > pH then unionised form > ionised form
if pKa < pH then ionised form > unionised form
What would the ratio be like if one local anaesthetic had a pKa of 10 and another had a pKa of 7?
The LA with a pKa value of 7 will have more unionised form and will work quicker
body pH is 7.4
the closer the pKa value of the local anaesthetic to 7.4, the faster it will work
What happens if body pH is lowered?
What does this mean about where local anaesthetic can be injected?
If the pH is lowered, there will be even less unionised form of LA and there is a greater difference between pH and pKa
if you inject LA around an abscess or inflamed tissue, it will not work due to local acidosis and lowered pH
What are the rules around ionised and non-ionised forms of local anaesthetic?
- Clinical onset is not the same for all local anaesthetics with the same pKa
- this may be due to the individual LAs ability to diffuse through connective tissue
- the closer the pKa to physiological pH, the faster the onset
What characteristic determines the duration of action of a local anaesthetic?
Protein binding
the more protein binding, the longer the duration of action
the drug is released from the protein over a longer period of time
the length of the intermediate chain joining aromatic and amide groups also has an influence
What is meant by potency?
What does it depend on?
The dose required to produce the desired effect
this depends on lipid solubility
a more lipid soluble drug will penetrate the cell membrane, meaning a smaller amount is required to produce a given effect
What does the ability to block neuronal conduction depend on?
Type of nerve fibre:
- the larger the fibre, the slower the onset
Location of the nerve fibre:
- is it outside or in the mantle?
- it will take longer for the LA to reach the nerve fibre if it is in the centre of the nerve, opposed to just under the membrane
When local anaesthetic is applied, what is one of the first sensations that is lost?
Pain
pain nerve fibres have a small diameter
What is the effect called that describes how the smaller the nerve fibres are, the more quickly they become numb?
Differential block
What is the % protein binding of lignocaine, bupivacaine and procaine?
Procaine - 65%
bupivacaine - 95%
procaine - 6%
bupivacaine will have the longest duration of action
What does the ability to block neuronal conduction depend on?
In which order is sensory function lost?
Ability to block neuronal conduction depends upon the type of nerve fibre
sensory function is lost in the following order:
- cold, warmth
- pain
- touch, deep pressure
- motor function
Why are local anaesthetics frequently given with a vasoconstrictor?
- To prolong action
- to reduce plasma levels so there is less risk of CNS effects
- ‘greater anaesthesia’ or reduced dose
- reduced operative haemorrhage (bleeding)
When should vasoconstrictors not be used with local anaesthetics?
They are not used when a structure is supplied by end-vessels
e.g. Fingers, toes, penis, ear lobule or ala of nose
What are two common vasoconstrictors that are used alongside local anaesthetics?
Adrenaline:
- stimulates a-adrenoceptors that constrict blood vessels
felypressin:
- this is an analogue of vasopressin
- it causes vasoconstriction but is less effective than adrenaline
- it has no effect on heart conduction/contraction
What are common combinations of local anaesthetics and vasoconstrictors?
- Lignocaine with adrenaline
- prilocaine with felypressin
What are the 2 main adverse effects of local anaesthetics?
- Hypersensitivity (allergic response)
- methaemoglobinaemia
What are the characteristics of a hypersensitivity reaction associated with local anaesthetics?
The anaphylactic reaction can range from a skin rash to full anaphylactic shock
it is common with ester LAs, but rare with amides
is often a reaction to preservatives, rather than the LA itself
Why does methaemoglobinaemia occur?
What are the associated symptoms?
It is the main toxic effect of prilocaine due to its metabolite 0-toludine
this oxidises ferrous to ferric ions
symptoms:
- cyanosis
- lethargy
- respiratory distress, which does not respond to oxygen
treatment:
- IV methylene blue - 1.5 mg per kg
How does the severity of side effects of LA toxicity change with plasma concentration?
At very low doses, LAs can stabilise the heart and be anti-arrhythmic
as plasma concentration increases, the severity of side effects increase
What are the side effects of local anaesthetics in order of increasing severity?
As plasma concentration of LA increases, the severity of the side effects increases from:
- Circumoral and tongue numbness
- Lightheadedness and tinutis
- Visual disturbances
- Muscular twitching
- Convulsions
- Unconsciousness
- Coma
- Respiratory arrest
- CVS depression
What are the first stages in treatment of local anaesthetic toxicity?
- Stop injecting the local anaesthetic
- call for help
A:
- maintain the airway
- if necessary, secure it with a tracheal tube
B:
- give 100% oxygen and ensure adequate lung ventilation
C:
- confirm or establish intravenous access
- Assess cardiovascular status throughout*
What are the further steps involved in treatment of LA toxicity?
D:
- control seizures
- benzodiazepine, thiopental or propofol
Consider drawing blood for analysis
In circulatory arrest:
- Start cardiopulmonary resuscitation
- use standard protocols
Give intravenous lipid emulsion
What are the toxic doses of lidocaine and bupivacaine?
Lidocaine:
- 3 mg/kg
- 7 mg/kg with adrenaline
Bupivacaine:
- 2 mg/kg
- 2 mg/kg with adrenaline also
What is the toxic dose of prilocaine?
6 mg/kg
or 8 mg/kg with adrenaline
