L30 - local anaesthetics Flashcards
types of local anaesthetic
regional anaesthesia
local infiltration
topical
regional anaesthesia
loss of sensation to a region or body part
local infiltration anaesthesia
cuts, skin incisions
topical anaesthesia
eye / skin (venepuncture)
non-pharmalogical anaesthesia methods
cold (below 8-10 degrees)
pressure
hypoxia
how does hypoxia act as an anaesthetic
makes the area go numb
reversible local anaesthetic
loss of sensation to a localised area
after a period of time, the nerve impulse will become normal
non-reversible local anaesthetic
phenol, ethanol, radio frequency, surgical
once used, nerve conduction is blocked forever (patients with chronic pain)
LA definition
A drug which reversibly prevents transmission of the nerve impulse in the region which it is applied without affected consciousness
mechanism of LA
At the site of injury, LA block sodium channels opening by binding to subunits from inside the membrane
- Na can no longer enter the cell
- depolarisation
- no action potentials = no pain flowing
endoneurium
a layer of connective tissue surrounding nerve fibres
fascicle
a bundle of nerves in the endoneurium
perineurium
surrounds the fascicles
epineurium
surrounds the perineurium
where does LS bind in a Na channel
S6 transmembrane domain from the inside, causing closure of the channel
how does LA travel across the membrane
only the unionised form can cross as it is liquid soluble (the majority is ionised)
which form of LA binds to the sodium channel
only the ionised / protonated form can bind to the channel
what determines speed of action of LA
% of unionised form of LA present
what does binding of LA to sodium channel do
- slows the rate of AP
- increases the threshold for stimulation
- reduces rate of conduction
- eventually blocks conduction completely
ideal LA
- reversible
- good therapeutic index (ratio of effective dose / legal dose)
- quick onset
- suitable duration
- no irritation even on repeated application
- no side effects
- no potential to induce allergy
- applicable by all routes
- cheap, stable, soluble
structure of LA
aromatic (lipophilic part)
intermediate chain
hydrophilic substituted amino acid (protein acceptor)
two types of LAs
amides
esters
how to know if a LA is an amides
…i…caine
how to know if a LA is an ester
…caine
onset of action
depends on their ability to go into the nerve cell and cross the membrane
- drug must be unionised
pH and onset of action
further away the pKa of LA from the body pH (7.4), there will be fewer in unionised form = slower onset
pH in inflammation
low - so LA less effective
differential block - type of nerve fibre
larger fibre = slower onset
differential block - location of nerve fibre
nearer the centre of the mantle = takes longer to work
what is commonly given with a LA
vasoconstrictors
action of vasoconstrictors
- prolong action
- reduce plasma levels
- greater anaesthesia or reduces dose
when should vasoconstrictors not be used
not used with LAs which are supplied by end-vessels
e.g., fingers, toes, penis, ear lobe
adrenaline
stimulation of alpha adrenoreceptors - constrict blood vessels
examples of vasoconstrictors
- adrenaline
- felypressin (less effective than adrenaline)
adverse effects of LAs
- hypersensitivity
- methaemoglobinaemia
hypersensitivity
- anaphylactic reaction
- ester> than amides
methaemoglobinaemia
Main toxic effect of prilocaine due to its metabolic O-toluidine, which oxidises ferrous to ferric ions
symptoms of methaemoglobinaemia
cyanosis, lethargy, respiration distress which does not respond to oxygen
dose of lidocaine
3mg/kg
with adrenaline: 7mg/kg
bupivacaine / levobupivacaine
2mg/kg
with adrenaline: 2mg/kg
prilocaine
6mg/lg
with adrenaline: 8mg/kg
treatment of LA toxicity
- stop injection with LA
- call for help
- A: open the airway
- B: give 100% oxygen and ensure adequate lung ventilation
- C: confirm or establish IV access
- D: control seizures
- consider drawing
treatment of LA toxicity - in circulatory arrest
- start cardiopulmonary resuscitation
- use standard ALS protocol
- give IV lipid emulsion
how do LA diffuse in to the body
outside the nerves - they then diffuse through the epineurium, perineurium and endometrium to act on the Na channels on nerve axons
(they are never injected into nerves)
-COO- link
ester
who initially used cocaine as a LA
Karl Koller
examples of amide LAs
bupivacaine
ropivacine
prilocaine
ligocaine
what determines potency of the LA
lipid solubility
duration of action in a more protein binding LA
More protein binding = longer the duration of action
potency
dose required to produce required effect
