Local Anesthesia Flashcards
Name the 3 mechanisms of action of local anaesthesia.
- stopping axonal conduction by blocking sodium channels in the axonal membrane
- passage of train of action potentials causes sodium channel to cycle through open and inactivated states
- non selective modifiers of neuronal function
What kind of channels do LAs bind most strongly to?
Inactivated and activated channels. Closed channels are blocked structurally and deactivated channels have a gating mechanism.
What is use dependency?
Depth of nerve block increasing with action potential frequency, in LAs which cause sodium channel to cycle through open and inactivated states.
How is selectivity achieved in LAs which are non-selective modifiers of neuronal function?
Deliver LA to a limited area, as local action is much greater than systemic action.
What are the 3 factors affecting LA function?
- lipid solubility (more lipophilic drugs are more potent)
- nerve fibre characteristics
- local pH
Name three LAs that are highly lipophilic.
Tetracaine, etidocaine, bupivacaine
Rank these factors in terms of effect on LA action: size, myelination, firing rate, location
Most effect: size (small) >
myelination (myelinated) >
firing rate (high) = location (circumferential/not deep)
:Least effect
How does pH affect LA activity?
LA molecules are weak bases. Alkaline pH increases LA activity, allowing LA to penetrate the nerve sheath and axon membrane to reach the inner end of the sodium channel.
Describe the distribution of LA.
- alpha phase: steep exponential LA decline, rapid distribution in blood and highly perfused organs
- beta phase: slower/linear rate of decline, distribution to less well-perfused tissue
What kind of LA has the most rapid onset?
LA that penetrates the axon most rapidly.
Distinguish the metabolism of Ester-type and Amide-type LAs.
Ester-type: metabolised by esterases in blood
Amide-type: metabolised by liver enzymes
What kind of LA dose is most likely to cause systemic toxicity?
•IV dose
•large dose
•excessive repeat dose
Why is LA sometimes combined with Epinephrine?
This prevents LA systemic distribution by reducing visceral vessel diameter.
Distinguish the characteristics of Ester-type and Amide-type LAs.
- Bond: ester bond vs amide bond
- Incidence of allergic reactions: low vs very low
- Metabolism: Plasma/tissue non-specific esterases vs Hepatic enzymes
When are Ester-type LAs and Amide-type LAs contraindicated?
Ester-type: PABA allergies, kidney disease
Amide-type: Liver disease
