Principles of Local Anaesthesia Flashcards
Describe the generation of a neuronal action potential
Depolarisation occurs, NA channels open, Na influx causing depolarisation till around +40mV then Na channels close, VGKC open, K efflux causing repolarisation till about -90mV, VGKC and channels shut
What determines resting potential of a neuronal cell?
K+ efflux down concentration gradient and K+ influx down electrochemical gradient (although membrane is slightly permeable to other ions too, hence why RP is -70mV not -92mV)
Definition of a local anaesthetic
Drug which reversibly blocks neuronal conduction when applied locally
2 groups of LA?
ester LAs, amide LAs
Example of ester anaesthetic?
Cocaine
Example of amide anaesthetic?
Lidocaine
Saying to remember a type of LA?
Ester smokes cocaine
What is the pKa of all LA?
Weak bases, pKa 8-9
What’re the 2 MOA of LAs called?
The hydrophilic pathway and hydrophobic pathway
Explain the hydrophilic pathway of LA MOA
- Once the unionized LA gets inside the neurone, the cationic form (BH+) of the LA is formed inside
- This can only bind with the sodium channel when it is open because the binding site is inside the channel
- Once inside the channel, it stereo-chemically inhibits the passage of sodium ions from the outside to the inside of the cell
Where must the LA be for the hydrophilic pathway
inside the neurone
Explain the use-dependency of the LA
the more active the cell is, the more frequently its sodium channel will be open and the more readily it will be blocked
Selectivity of LA? what impact does this have
- They are not super selective so they will inhibit motor neurons as well as nociceptive
Explain the hydrophobic MOA of LA
- LA passes into the membrane of the neurone in the unionized form
- Some highly lipid soluble LAs can drop straight into the sodium channel
- They then become ionized in the sodium channel and block the channel
Effects of LA (4)
- Prevent generation and conduction of APs
- Do NOT influence resting membrane potential
- May also influence channel gating (they have preference to bind to the inactivated state)
- Selectively block small diameter fibres and non-myelinated fibres
What type of fibre do LA have selectivity for
small diameter fibres and non-myelinated fibres
What problems does infected tissue pose re. GA?
Tends to be acidic so a higher proportion of the LA will be ionised so harder to treat infected tissue with LA
6 ROA of LA?
- Surface anaesthesia
- Infiltration anaesthesia
- Intravenous regional anaesthesia
- Nerve block anaesthesia
- Spinal anaesthesia
- Epidural anaesthesia
Surface anaesthesia: type of surface? How is drug administered? Risk?
- Mucosal surface (mouth, bronchial tree)
- Spray (or powder)
- High concentrations systemic toxicity
Infiltration anaesthesia: where? Used for? Coinjected with…? Why coinjected with X?
- Directly into tissues sensory nerve terminals
- Minor surgery
- Adrenaline co-injection (vasoconstrictor so the anaesthetic will be held at the site of action so lower doses can be used and won’t cause systemic toxicity) (NOT do in extremities as can cause ischaemia)
Intravenous regional anaesthesia: how? Used for? Risk?
- Use a pressure cuff
- I.V. distal to pressure cuff
- Limb surgery
- Systemic toxicity of premature cuff release
Nerve block anaesthesia: where? speed of onset? size of dosage? Coinjected with? Why coinjection?
- Close to nerve trunks e.g. dental nerves
- Widely used – low doses – slow onset
- Vasoconstrictor co-injection (adrenaline - anaesthetic will be held at the site of action so lower doses can be used and won’t cause systemic toxicity)
Spinal anaesthesia: where? Used for what? Side effect, caused by what? Why does this side effect occur? Coinjected with, why?
- Sub-arachnoid space – floods around spinal roots
- Abdominal, pelvic, lower limb surgery
- Decrease BP prolonged headache, this is because preganglionic sympa fibres are narrow and unmyelinated so sympa outflow can be blocked too
- Mix it with glucose (to increase specific gravity)
Epidural anaesthesia: where? Used for? Onset speed? Risk? Dosage? Effect on BP?
- Fatty tissue of epidural space – spinal roots
- Uses as for spinal anaesthesia and painless childbirth
- Slower onset – higher doses are needed because you’re injecting outside of the spinal cord, this increases risk of systemic toxicity
- More restricted action – less effect on BP
