local anaesthetics

Question 1

how do local anaesthetics work

Answer 1

reversible blocking the generation and conduction of APs via blocking voltage gated sodium channels

Question 2

what is mechanism of local anaesthetics

Answer 2

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

Question 3

how does LA structure affect membrane permeability and how they are administered

Answer 3

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

Question 4

what is the most significant property of LAs in determining potency

Answer 4

lipid solubility

Question 5

what affects duration of block

Answer 5

capacity of LA to bind plasma and tissue proteins

Question 6

how does pKa of the LA affect speed of block

Answer 6

pKa= pH which substance is 50% ionic

lower pKa greater fraction exists in uncharged form, so faster blockade

Question 7

how does size of fibre effect block

Answer 7

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

Question 8

in terms of sensation, what is blocked first-last

Answer 8

degree of block of sensations: pain>cold>warm>touch>pressure>motorneurones

Question 9

how does structure affect how LA stability and metabolism

Answer 9

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

Question 10

what are CNS side affects of LAs in low concs

Answer 10

tinnitus, numbness of tongue, blurred vision, drowsiness

Question 11

what are CNS side affects of LAs in large concs?

Answer 11

agitation with hyperactivity, occasional convulsions followed by CNS depression and respiratory depression

Question 12

what are CV effects of LAs

Answer 12

vasodilation and slowing of heart rate leading to hypotension

Question 13

what metabolite of LAs is associated with hypersensitivity reactions

Answer 13

pABA, metabolite of amino ester LAs

Question 14

what are methods of administration of LAs

Answer 14

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

Question 15

how would you anaesthetise an area served by a specific nerve

Answer 15

nerve block anaesthesia: drug injection close to nerve trunk

Question 16

how is spinal anaesthesia administered, what is it used for

Answer 16

injection into subarachnoid space between L2-5, used for major surgery where patient still need to be awake, e.g C section

Question 17

how is epidural anaesthesia administered

Answer 17

injection into epidural space (outside dura mater) which causes direct action on nerve roots and spinal cord, used in obstetrics