Local Anaethesia Flashcards
What is ‘general’ anaesthesia?
total loss of sensation
What are the 3 types of local anaesthetics?
- Regional
- Infiltration
- Topical
What is regional anaesthesia?
loss of sensation to a region or part of the body whilst patient is awake
What is ‘local infiltration’ anaethesia?
anaesthesia injected just at site e.g. cuts, skin incisions
What is ‘topical’ anaethesia?
put topically on area e.g. eye, skin
Define an anaesthetic drug
induces partial or total loss of sensation
Define amnesia
lack of response and recall to noxious stimuli, unconscious
Define analgesia
pain relief
Define akinesia
Immobilisation/paralysis
What is the triad of balanced anaesthesia? What is the purpose?
The triad: pain relief (analgesia), unconsciousness (amnesia) and muscle relaxation.
Purpose:
- Combination of agents used
- Safer than large dose of a single agent
- Maximises benefit of individual agent
- Minimises adverse effects
What are the non-pharmalogical types of anaesthesia?
cold, pressure, hypoxia
The pharmalogical types of anaesthesia can be reversible or irreversible. What happens during irreversible anaesthesia? When would this be done?
- Nerve conduction is blocked forever
- Typically used in people with chronic pain
What are 3 examples of irreversible anaesthesia?
Phenol, ethanol (destroy nerves), radiofrequency
What 3 characteristics defines a ‘local’ anaesthetic drug?
- reversibly prevents transmission of the nerve impulse
- in the region to which it is applied
- without affecting consciousness
Describe the 1st, 2nd and 3rd order neurons in the general pain pathway
First order neuron:
- Detect painful stimuli
- Generates an action potential
- Takes information from site of injury to spinal cord to synapse with 2nd order neuron
Second order neuron:
- Takes informatin across the midline
- Ascends in the lateral spinothalamic tract to reach the VPL/VPM of the thalamus
- Synapses with 3rd order neuron
Third order neuron:
- Project via the posterior limb of the internal capsule to terminate in the ipsilateral postcentral gyrus (primary somatosensory cortex)
Briefly describe the mechanism of an action potential
- A stimulus first causes sodium channels to open.
- Sodium ions enter neuron (due to gradient)
- Membrane potential increases from -70mV (resting potential) –> this is depolarisation
- When the threshold of -55mV is reached, an action potential is fired (‘all or nothing’)
- Membrane potential reaches around +30mV
- Potassium channels open and sodium channels close
- Potassium leaves cell and membrane potential starts to become more negative again –> repolarisation
- The action potential actually goes past -70 mV (a hyperpolarization) because the potassium channels stay open a bit too long.
- Gradually, the ion concentrations go back to resting levels and the cell returns to -70 mV (resting potential)
How do local anaesthetics affect the action potential?
Local anaesthetics block the alpha subunit of sodium channels so impulse is stopped as ion conduction pore is blocked. Brain is not receiving any information about pain.
Describe the shape of 1st order neurons in the pain pathway. Where is there cell body located?
- These are pseudounipolar neurons which have cells bodies within the dorsal root ganglion.
- They have one axon which splits into two branches, a peripheral branch (which extends towards the peripheries) and a central branch (which extends centrally into the spinal cord/brainstem).
Where are the cell bodies of the 2nd order neurons of the pain pathway located?
Rexed laminae of the spinal cord, or in the nuclei of the cranial nerves within the brain stem
Where do the cell bodies of the 3rd order neurons of the pain pathway lie?
The cell bodies of third-order neurons lie within the VPL or VPM of the thalamus.
Via which limb of the internal capsule does the 3rd order neuron of the pain pathway use to reach the somatosensory cortex?
Posterior limb
What do voltage-gated sodium channels normally consist of?
Voltage-gated sodium channels normally consist of an alpha subunit that forms the ion conduction pore and one to two beta subunits that have several functions including modulation of channel gating. Expression of the alpha subunit alone is sufficient to produce a functional channel.
What is a sodium channel composed of?
- Composed of an alpha subunit; forms the ion conduction pore
- The a-subunit has 4 repeat domains; labelled I to IV; each containing 6 membrane spanning segments labelled S1 to S6
- One to two beta subunits
Which transmembrane segment in sodium chanenls is most important in the channel opening?
S4 segment acts as channel’s voltage sensor –> conformational changes in S4 causes channel to open
What transmembrane segment in the sodium channel does LA bind to? What is the effect of this?
LA binds to S6 segment which causes inactivation of opening of channel to stops sodium entering:
- This slows the rate of action potential
- Increases the threshold for stimulation of action potential
- Reduces rate of conduction (eventually blocks conduction completely)
LA’s exist in 2 forms; ionised and unionised. Which form can cross the membrane? What happens when it does? Why is it essential for LA to cross the membrane?
- LA have to cross cell membrane in order to bind to the sodium channel from the inside
- Only unionised form can cross cell membrane (lipid soluble)
- Once unionised form crosses cell membrane, it becomes ionised
- Ionised form only can bind to sodium channel
Explain why different LA’s have different speeds on onset
- The pKa of a local anaesthetic determines the amount which exists in an ionised form at any given pH.
- At physiological pH (7.4) all local anaesthetics are more ionised than unionised (as all the pKa values are greater than 7.4)
- However, the proportions vary between the drugs
- At physiological pH (7.4) all local anaesthetics are more ionised than unionised (as all the pKa values are greater than 7.4)
- Therefore, the drug which is more unionised at physiological pH will reach its target site more quickly than the drug which is less so (this explains why lignocaine has a faster onset of action than bupivacaine
Describe the anatomy of a nerve from outer to inner layers
A nerve is an enclosed, cable-like bundle of axons in the PNS which provides a structured pathway that supports the impulses transmitted along each of the axons.
- Each nerve contains main axons (fibres)
- Within a nerve, each axon is surrounded by a layer of connective tissue called the endoneurium
- The axons are bundled together in groups called fascicles; each fascicle is wrapped in a layer of connective tissue called the perineurium
- Finally, the entire nerve (groups of fascicles) is wrapped in a layer of connective tissue called the epineurium.
Local anaesthetic has to pass through; the epineurium, perineurium and the endoneurium in order to work. Can take time for LA to start working.
what is the ‘endoneurium’?
Within a nerve, each axon is surrounded by a layer of connective tissue called the endoneurium
what is the ‘perineurium’?
The axons are bundled together in groups called fascicles; each fascicle is wrapped in a layer of connective tissue called the perineurium
What is the epineurium?
Finally, the entire nerve (groups of fascicles) is wrapped in a layer of connective tissue called the epineurium.
What is a bundle of axons called in the CNS?
Tract
Which spinothalamic tract is pain information carried in?
Lateral
Which order nerves in the pain pathway does a spinal/epidural block target?
Second order neurons
What is the therapeutic index?
The therapeutic index is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.
Local anaesthetics consist of 3 components. What are these?
- Lipophilic aromatic ring/residue
- Intermediate ester or amide chain
- Terminal hydrophobic amino group
How can you tell if a LA is an amide or an ester?
If a local anaesthetic has an ‘i’ anywhere before the ‘caine’ – it is an amide
What does the onset of action of LA’s depend on?
- Depends on amount of unionised/ionised form
- More unionised form = faster onset of action
What does pKa equal?
- pH at which the unionised form and ionised forms of LA’s are equal
- If pKa > pH: unionised form > ionised form
What is the body pH?
Body pH is 7.4 so if pKa of drug is larger than this, then unionised form > ionised form
The further away the pKa of a LA gets from the body pH, how does this affect the onset of action?
- Further away the pKa of LA from body pH, the lesser is the unionised form
- Examples:
- LA agent A pKa: 8.1
- LA agent B pKa: 7.8
- At body pH 7.4:
- Unionised form of agent B > agent A
- Agent B quicker onset
Lidocaine has a pKa of 7.8. Bupivacaine has a pKa of 8.1. Which has a faster onset?
pKa of Lidocaine is closer to body pH, therefore more unionised form available so works quickest
How can pus/inflammation affect the onset of LA?
- If there is any pus or inflammation, this changes the pH
- Pus pH is around 6.8
- The difference between the pH and pKa increases –> the amount of unionised drug is reduced significantly and the LA may not be as effective as is normally is
How does inflammation affect the pH of surrounding tissue?
Inflammation results in local acidosis which decreases pH of surrounding tissue.
Why is the clinical onset is not the same for all local anaesthetics with the same pKa?
This may be due to the individual local anaesthetics ability to diffuse through connective tissue.
Generally, the closer the pKa to physiological pH the faster onset. What are the 2 exceptions to this?
chloroprocaine and benzocaine
What 2 factors affect the duration of action of LAs?
- Protein binding
- Length of the intermediate chain joining the aromatic and amine groups
How does protein binding affect the duration of action of LAs?
- The more the LA is bound to protein, the longer the duration of action:
- Lignocaine 65%
- Bupivacaine 95%
- Procaine 6%
What is ‘potency’ of LAs?
Potency; dose required to produce the desired effect
What does potency of LAs depend on?
- Depends on ‘lipid solubility’
- More lipid soluble drug penetrates the cell membrane –> more potent
- Smaller amount required to produce a given effect
What is ‘differential blockade’ of LAs?
The clinical phenomenon that nerve fibres with different functions have different sensitivities to local anaesthetic blockade.
What 2 factors affect the ability of an LA to block nerve conduction?
- Type of nerve fibre; Larger fibre = slower onset
- Location of nerve fibre; outside or in the mantle –> inside the mantle will take longer to be blocked
What are the 3 different types of nerve fibres?
A, B and C
What are the 4 different subtypes of A nerve fibres?
A-alpha
A-beta
A-gamma
A-delta
Function of;
a) a-alpha fibres
b) a-beta fibres
c) a-gamma fibres
d) a-delta fibres
Function of;
a) b fibres
c) c fibres
Why are pain fibres blocked first?
Pain fibres are smaller. Ability to block neuronal conduction depends upon type of nerve fibre.
What is the order of loss of sensory function?
- Cold, Warmth
- Pain (‘first pain’ (Ad fibres), then ‘second pain’ (C fibres)
- Touch, Deep pressure
- Motor function
LAs are frequently given with a vasoconstrictor. What are 2 major vasoconstrictors are used?
- Adrenaline
- Felypressin
Why are LAs frequently given with a vasoconstrictor?
In order to reduce blood supply to area so LA can stay there for longer:
- prolong action
- reduce plasma levels (less risk of CNS effects)?
- ‘greater anaesthesia’ or reduced dose
- reduced operative haemorrhage
Vasoconstrictors are not used with LAs which are supplied by end-vessels. Why? What are some example of areas supplied by end-vessels?
Will lead to necrosis/ischaemia:
- fingers and toes
- penis
- ear lobule, ala of nose
how does adrenaline produce vasoconstriction?
Stimulation of a adrenoceptors constrict blood vessels
Why is there a higher % of adrenaline used in dental surgery?
dental is highly vascular
What are the side effects of adrenaline being used alongside LAs?
Side effect; large amount of adrenaline can lead to panic attack/heart palpitations
What is Felypressin an analogue of?
Vasopressin
Compare the effects of Felypressin to adrenaline.
- Vasoconstriction but less effective than adrenaline
- BUT no effect on heart conduction/contraction
LAs can lead to hypersensitivity reactions. Is this more common in ester or amide LAs?
- A problem with ester LAs but very rare with amides.
- May also be a reaction to preservatives
LAs can also lead to methaemoglobinaemia. What is this? Why is this a problem?
- Elevated methaemoglobin in the blood
- Methaemoglobin cannot bind O2
- Symptoms - cyanosis, lethargy and respiratory distress which does not respond to oxygen.
Toxicity of lidocaine:
Treatment of LA toxicity?
- Stop injecting the LA
- Call for help
- A: Open the airway
- B: Give 100% oxygen and ensure adequate lung ventilation
- C: Confirm or establish intravenous access
- Assess cardiovascular status throughout
- D: Control seizures:
- benzodiazepine, thiopental or propofol
Treatment of circulatory arrest due to LAs?
- Start cardiopulmonary resuscitation
- Use standard ALS protocols
- Give intravenous lipid emulsion
Local anaesthetics produce reversible conduction block. True or false
True
Local anaeshetics work by blocking K+ conduction. True or false
False, Local anaesthetics block sodium channels
Local anaesthetics block sodium channels from outside. True or false
False; block from inside
Local anaesthetics are injected into the nerves for quick action. True or false
False; Local anaesthetics are never injected into the nerves as this will cause damage to the nerves. Local anaesthetics are injected outside the nerves and then they diffuse through epineurium, perineurium and endoneurium to act on the sodium channels on nerve axons.
Local anaesthetics are safe and have no side effects. True or false
False; Local anaesthetics can cause serious toxicity if a larger than safe dose is used or if they are injected intravascularly.
-COO- link between the aromatic and amide group indicates an ester type LA. True or false
False; Esters contain a carbonyl center, and contain C–C–O and O–C–O angles.
Bupivacaine is an amide local anaesthetic. True or false
True; Bupivacaine, ropivacaine, prilocaine and lignocaine are commonly used amide local anaesthetics. If in the name of the local anaesthetic there is the vowel ‘i’ before the ‘caine’ in the end, the local anaesthetic is an amide. i.e. bup - i - va - caine
Lipid solubility determines the duration of action. True or false
False; Lipid solubility determines the potency of a local anaesthetic.
Adrenaline decreases the safe dose of local anaesthetics. True or false
False; Adrenaline increases the safe dose of local anaesthetics by causing local vasoconstriction and delaying the absorption of local anaesthetic agents.
Tinnitus is one of the initial presenting symptoms of local anaesthetic toxicity. True or false
True; Tinnitus, altered sensation around mouth, blurred vision and altered consciousness are usual presenting symptoms of local anaesthetic toxicity.
Cardiovascular toxicity is before Central nervous system symptoms (seizures) in LA toxicity. True or false
False; The concentration of local anaesthetics that causes CVS toxicity is about twice the concentration that causes central nervous system symptoms i.e. seizures.
Intralipid should be given immediately if LA toxicity is suspected. True or false
False; Intralipid should be given only in severe cases of LA toxicity.
Hypersensitivity reactions are seen rarely with amide LAs. True or false
True; Hypersensitivity reactions are very rare with amide LAs.
