Local anaesthetics Flashcards
What is the main difference between general vs local anaesthetics?
Local anaesthetics; drugs which reversibly block neuronal conducting when applied locally
General anaesthetics: drugs which induce a state of unconsciousness that is systemic
Recall the main steps in the propagation of an AP
[-70mV resting potential]
Depolarisation: Resting VG Na+ channel opens and there is rapid depolarisation to reach threshold potential of -50mV
Repolarisation: Na+ channels close (inactivated), K+ channels open
Hyperpolarisation: Na+ channels restored to resting state, K+ channels open (refractory period)
Return to resting potential: Na+ and K+ channels are returned to resting state due to Na+/K+ ATPase.
What is the MOA of local anaesthetics?
Block voltage gated Na+ channels
What are the three main structural features of LAs?
Aromatic region
Ester/amide bond
Tertiary amine side chain
Which is the LA that is an exception to the 3 main structural features?
Benzocaine; no tertiary amine side chain.
Weak, lipid soluble LA -> useful as a surface anaesthetic.
Describe the hydrophilic pathway of LAs
LAs are weak bases so are largely ionised.
Only unionised form can diffuse through connective tissue sheath.
Once it passes into axon -> only the ionised form has the LA action.
Blocks open NA+ channel from inside by stereochemical binding.
Use-dependent block
Describe the hydrophobic pathway of LAs
Applicable to lipid soluble LAs e.g. benzocaine
Able to diffuse through axonal membrane, become ionised and block Na channel when closed.
Not use-dependent
What are the main effects of LAs?
Reduce generation and conduction of APs
Do not influence resting membrane potential
Influence; channel gating (keep in inactivated state) and increase surface tension
Selectively block; small diameter and unmyelinated fibres
Why are LAs not typically used in infected tissue?
LAs are weak bases (pKa 8-9).
Infected tissue is acidic so most LA if injected will be in ionised form therefore less are able to diffuse across axon and is less effective.
Name the six routes of administration for LAs
Surface anaesthesia Infiltration anaesthesia IV anaesthesia Nerve block anaesthesia Spinal anaesthesia Epidural anaesthesia
What is meant by surface anaesthesia and what is the disadvantage of this method?
Anaesthesia applied to a mucous membrane e.g. mouth, bronchial tree)
Spray or powder
High concentrations needed - possible systemic toxicity
What is meant by infiltration anaesthesia?
Anaesthesia applied subcutaneously -> act on sensory nerve terminals
Used in minor surgery
Adrenaline co-injection
Why may you co-inject adrenaline when giving some types of LAs and what must you be careful about when injecting it?
Adrenaline is a vasoconstrictor;
- Able to localise LA as it slows diffusion rate, so it is more effective
- Use at lower concentrations, reduce chances of systemic toxicity
Must not inject into extremities e.g. hand and toes as this will stop blood flow there.
What is an alternative to adrenaline to co-inject with some types of LAs?
Felypressin; it is a V1 receptor agonist, Vasopressin analogue -> vasoconstriction
What is meant by IV anaesthesia and what is the risk?
Use pressure cuff (leave for at least 20mins) and administer distally
Used in limb surgery
There is a risk of systemic toxicity if the pressure cuff is released to early; may result in bolus of LA -> travel to heart -> brain
