local anesthetics Flashcards
general chemical structure of LA
lipophilic grp - amide/ester - ionisable group
weak base, less effective when delivered to acidic tissue (accelerate onset by sodium bicarbonate into soln)
which type of LA more prone to hydrolysis
ester links – shorter duration of action
ester type rapidly hydrolysed by butyrylcholinesterases in blood
PK of LA
onset – immediate as drug delivered directly to target site
offset/toxicity– absorption/distribution of drug
PK of LA
onset – immediate as drug delivered directly to target site
offset/toxicity– absorption/distribution of drug
why is epinephrine often injected w LA
vasoconstrictor, reduce blood flow to the region, maintains high LA conc at target site, duration of action longer
how is amide type LA hydrolysed
in the liver by microsomal cytochrome P450
excreted by kidneys
- reduced by liver disease/reduced hepatic blood flow /any meds reducing cP450 activity
how LA works
binds to receptors near intracellular end of Na+ channels and inhibit the influx of Na+
greater affinity for receptors within Na+ channels during activated/inactivated states than in resting state
does LA have anti-inflammatory effects?
yes
LA shows voltage and time-dependent blockage
effect more marked in rapidly firing fibres
factors affecting susceptibility of nn fibres to LA
more susceptible if:
smaller diameter, unmyelinated fibres (myelinated – need to excite a few node of Ranvier
faster firing frequency (sensory>motor)
fibres that are more circumferentially located in large nerve trunks – first to be exposed to LA
LA w diff duration of effect
short acting (ester link): procaine (45-60mins)
medium acting: lidocaine (1-2h)
long acting: bupivacaine (4-8h)
list some systemic toxicity of LA (from rapid absorption/accidental intravascular administration)
CNS: sleepiness, restlessness, numbness ard mouth, nystagmus (uncontrolled eye mvmt), muscle twitching, seizures, coma
CVS: systemic hypotension, arrhythmia, indirect effects on autonomic NS
haematology: prilocaine metabolite may cause methemoglobinema
allergy to metabolites of ester type LA
