local anaesthetics Flashcards
definition of LAs
drugs that cause loss of nociception by blocking afferent activity from specialised nociceptors that respond to tissue damage by intense chemical, mechanical or thermal stimulation
LA’s mechanism of action?
blocks Na channels in axonal membrane hence preventing Na+ entry
do LAs work better when you are in pain or no pain? why?
in pain
reason:
1. in pain, there are many action potentials being fired.
2. Na channels in such circumstances are cycling through open/activated states and inactivated states.
3. LAs have higher affinity for inactivated states and gain access to Na channels more readily when they are open
how to achieve selectivity for LAs? (recall that LAs are non selective)
deliver LA to a limited area
how to increase LA’s duration of action
- increasing dose
- add vasoconstrictor so less is loss to systemic circulation
what are 3 factors affecting onset of LA
- lipid solubility of LA
- nerve type
- pH
how does lipid solubility affect onset of LA
more lipid soluble LAs can pass through lipid bilayer better –> can act longer hence more potent
how does nerve type affect onset of LA
- smaller > bigger nerves. smaller nerves are easier to get to than bigger nerves
- sensory > motor nerves. sensory nerves have higher frequency of firing so there’s more open Na channels for LA to bind to
- circumferential > deep. circumferential nerves are easier to get to via topical administration than deep nerves
- myelinated > non-myelinated. myelinated nerves are easier to get to
rmbr that size matters more than myelination!
does alkaline or acidic pH cause better onset of LA? why?
alkaline.
reason:
1. in alkaline pH proportion of ionised/protonated LA molecules is low
2. more LA molecules can pass through lipid bilayer and bind to Na channel
how to accelerate onset of action of LA?
add NaHCO3 to solution to increase pH.
LAs are weak bases. making environment more alkali reduces ionisation so more unionised LA can enter cells.
which type of LA is more prone to hydrolysis by esterases in blood and tissues?
LAs with ester bonds (ester type LA).
hence ester type LA have a shorter duration of action compared to amide type LAs
which type of LA has a lower incidence of allergic reactions? why?
amide type LA.
ester type LA is hydrolysed to PABA derivatives which can cause allergic reaction in small percentage of population
what metabolises ester and amide type LAs respectively?
ester type –> plasma/tissue non-specific/blood esterase
amide type –> hepatic enzymes (eg. CYP450)
how to prevent toxicity of LAs?
combine LA with epinephrine which prevents systemic distribution as epinephrine reduces vessel diameter
how does toxicity of LAs come about?
- unintended large dose of LA if injected IV –> systemic toxicity
- overdose of LA injected locally leading to high levels of blood following absorption
recall that the overdose @ local site will have later onset of toxic symptoms compared to systemic injection
