local anaesthetics

Question 1

how can action potentials be studied

Answer 1

Tetrodotoxin blocks neuronal voltage gates sodium channels: abolishes action potentials but not initial depolarization.

TEA blocks neuronal voltage gated potassium channels: slows repolarization and no hyperpolarization.

ouabain inhibits Na K atpase reduces AP progressively until membrane Na gradient is so reduced no ap can fire.

Question 2

describe myelination

Answer 2

formed by proteins and phospholipids
insulating layer around axon membrane to allow quick AP transmission
provided by glial cells
PNS: schwann cells
CNS: astrocytes microglia oligodendrocytes

better at increasing speed of transmission than increasing axon diameter

Question 3

what is saltatory conduction

Answer 3

rapid AP propagation of the AP between nodes of ranvier (where ion channels are)

Question 4

describe VGIC structure

Answer 4

4 subunits 6TM for Kv (not connected)
4 domains 6TM for Nav and Cav
auxillary 1TM beta subunits

Question 5

describe how VGSC are related to pain

Answer 5

loss of function mutations in Nav1.7 linked to congenital insensitivity to pain
(condition which inhibits ability to percieve pain.)
in terms of pain:
stimulus at sensory terminal (from pain) > transduction element activation leading to ion flux > VGSC amplifies this flux which allows membrane potential to reach threshold and transmits pain information to spinal cord

Question 6

what is the function of local anaestethics

Answer 6

inhibit VGSC at the intracellular side to block the conduction of action potentials to block pain.

Question 7

give examples of LA’s

Answer 7

esters: metabolised by non specific esterases in plasma and tissues
procaine
proxymetacaine
cocaine

amides : more stable longer half life only metabolised by liver amidases in liver
lidocaine
prilocaine
benzocaine

Question 8

what are side effects of LA’s

Answer 8

cns: agitation, confusion, tremors, respiratory depression
CVS: myocardial depression and vasodilatation
other: hypersensitivty (allergic)

must have controlled administration.

Question 9

what causes different sensitivities to LA’s

Answer 9

myelinated and thicker axons ex: hardest Aalpha (motor) Abeta (touch) Agamma (motor) Adelta (pain) easier
C fibres (pain) transmitting pain signals easiest to block
LA’s reduce pain at lower doses more rapidly than affecting sensation and motor functions

Question 10

what does LA being weak bases cause

Answer 10

more ionised form exists if they are lower pH than their pka
only unionized forms can cross plasma membrane to act on vgsc