local anaesthetics Flashcards
how do local anaesthetics work
reversible blocking the generation and conduction of APs via blocking voltage gated sodium channels
what is mechanism of local anaesthetics
they plug sodium channel from the inside
block develops faster and is greater when nerve is conducting APs at high frequency
reason for this is that inactivated sodium channels have higher affinity for local anaesthetics than resting ones, also when nerve depolarises it drives LAs into the sodium channel
this process is called use-dependency block
how does LA structure affect membrane permeability and how they are administered
most LAs are weak bases, charged forms cannot penetrate axon membrane
uncharged forms diffuse across
once inside 80-90% become charged at intracellular pH
they are administered as water soluable hydrochlorides
after injection the tertiary amine base is liberated by alkaline pH of tissue fluids
what is the most significant property of LAs in determining potency
lipid solubility
what affects duration of block
capacity of LA to bind plasma and tissue proteins
how does pKa of the LA affect speed of block
pKa= pH which substance is 50% ionic
lower pKa greater fraction exists in uncharged form, so faster blockade
how does size of fibre effect block
thin fibres are blocked more easily than thicker ones
myelinated ones are blocked more readily than non myelinated ones
small diameter C and Adelta pain fibre, fire at high frequency so size and rate means they are very easily blocked and more selectively blocked than Aalpha fibres
in terms of sensation, what is blocked first-last
degree of block of sensations: pain>cold>warm>touch>pressure>motorneurones
how does structure affect how LA stability and metabolism
amino ester LAs: relatively unstable in solution, rapidly hydrolysed by plasma cholinesterase and other esterase’s
amino amide LAs: stable in solution, slowly metabolised in liver by hepatic amidases
what are CNS side affects of LAs in low concs
tinnitus, numbness of tongue, blurred vision, drowsiness
what are CNS side affects of LAs in large concs?
agitation with hyperactivity, occasional convulsions followed by CNS depression and respiratory depression
what are CV effects of LAs
vasodilation and slowing of heart rate leading to hypotension
what metabolite of LAs is associated with hypersensitivity reactions
pABA, metabolite of amino ester LAs
what are methods of administration of LAs
topical application for surface anaesthsia e.g lidocaine or benzocaine
drug injected into tissue for inflitration anaesthesia e.g lidocaine and prilocaine
injected LAs are usually supplemented with vasoconstrictors to delay absorption which prolongs duration of action and reduces risk of systematic toxicity, lowers dose required
examples of vasoconstrictor adjuncts are (nor)adrenaline and vasopressin
how would you anaesthetise an area served by a specific nerve
nerve block anaesthesia: drug injection close to nerve trunk