28. Principles of local anaesthesia Flashcards
What pH are local anaesthetics?
High - all LAs are weak bases, so are pH dependent to have an effect
What do LAs generally do?
Block sodium ion channels - preventing neuronal depolarisation
What 3 structures do all LAs have in common?
- Aromatic region (benzene)
- Basic amine side chain (tertiary)
- Linked by ester or amide bond
What are the 2 different groups of LAs and give examples?
- Esther LA - cocaine
- Amide LA - lidocaine
2 different linking of benzene and amine gives rise to these groups
Which LA is an exception to the general structure of LAs and why, and what is it used for?
Benzocaine
• Doesn’t have the basic amine side chain
• Has an alkyl group instead
• Still has weak LA properties and is lipid soluble
- Used as surface anaesthetic
- Useful in throat lozenges
How does LA go from being injected close to sensory pain-conducting neurones, to blocking their effect?
- Unionised (lipid-soluble) form passes through the connective tissue sheath
- Passes through the lipid bilayer and gains access inside the sensory axon
- LA becomes ionised (polar) inside axon, due to acid (physiological) environment
- Ionised form has anaesthetic properties, and binds to the inside of the of VGSC
- VGSC has to be open
Hydrophilic pathway - uses use -dependency
How is the hydrophobic pathway of LAs different to the hydrophilic?
- More important for the more lipid-soluble LAs
- As the unionised form cross the axonal membrane, some can convert into the cation ionised form and block the ion channel
- Can drop into a closed channel as well as an open channel
Do LAs influence the resting membrane potential?
No
Do LAs influence channel gating?
Yes
How does an LA having a higher affinity for the inactivated state of the channel affect the refractory period?
Prolongs it
What type of fibres do LAs selectively block?
- Smaller diameter fibres
* Non-myelinated fibres e.g. pain C-fibres
How is using an LA on infected tissue different and why?
- More difficult
* Tend to be acidic, so more LA becomes ionised and harder to enter axon
What are the different routes of LA administration?
- Surface
- Infiltration
- IV regional
- Nerve block
- Spinal
- Epidural
Can surface LA lead to systemic toxicity?
Yes, at high concentrations
How is infiltration anaesthesia administered?
- Subcutaneously
- Co-injected with adrenaline, as it causes vasoconstriction (apart from extremities to prevent ischaemic damage)
- This increases duration and reduces incidence of systemic effects
When and how is IV regional anaesthesia administered?
- Limb surgery?
- Administered distal to pressure cuff
- Cuff should be kept on for 20mins minimum
- LA diffuses from vein into tissue
- Premature cuff release can cause systemic toxicity
What is nerve block anaesthesia and how is it administered?
- LA injected close to nerve trunks e.g. dental nerve trunks
- Slow onset - many membranes to cross
- Co-injection with vasoconstrictor
Describe spinal anaesthesia, and when is it used?
- LA injected into sub-arachnoid space
- Action on spinal roots (intrathecal)
- Can be mixed with glucose to increase specific gravity - control
- Abdominal, pelvic and lower limb surgery
- LA mixes with CSF (injected at L3/4)
Describe the side effects of spinal anaesthesia
- Decreased BP - LA acting on small-diameter pre-ganglionic sympathetic neurones - bradycardia and vasodilation
- Prolonged headache - accesses the brain
How is the onset and dose of epidural different to spinal anaesthesia?
- Slower onset
* Higher doses required
What is the advantage of epidural anaesthesia compared to spinal?
- More restricted action
* Less effects on BP
How is lidocaine and cocaine metabolised?
- Lidocaine - hepatic N-dealkylation
* Cocaine - hepatic and plasma metabolism by non-specific esterases
Do amides or esters have a longer duration of action and why?
Amides as they are more resistant to metabolism
Why is Bupivacaine used for and what is it’s duration of action?
Epidural anaesthesia (half-life: 6 hours - long)
What are the unwanted effects of cocaine?
Sympathetic
• CNS: euphoria, excitation (slow NA re-uptake)
• CVS: increase CO, vasoconstriction, increased BP, cardia arrhythmias
What are the unwanted effects of lidocaine?
- CNS: stimulation, restlessness, confusion (GABAergic neurones are sensitive to LA - paradoxical, then depressive symptoms)
- CVS: myocardial depression, vasodilation, decreased BP (NA channel blockade)
