Local Anaesthetics Flashcards
basics of how LA work
stop nerve conduction by blocking the voltage-gated Na+ channels
what part of the nervous system do LAs work on
peripheral nervous system (doen’t touch CNS)
work on first order afferent receptors
what do the connective tissue layers in peripheral nerves act as
diffusion barriers
what factor determines which nerve will be affect by LA first , when they are in similar proximity to the LA
number of membranes that are barriers
what is the general rule for anaesthetising and weaning out
in general anaesthetised first, tends to be weaned out first
what type of molecule can cross connective tissue nerve membranes
lipophillic
aromatic ring
how can the lipophilic characteristics of LA influence how they perform
adheres, penetrates the membrane easier, like to be around fat - take longer to leave, will work in certain areas longer
fat allows to stay in nerve for longer
Cannot be too great affinity as can stay in fat and not reach nerve
what is the order of blockage by LA in different nerve fibres
A delta
C
A beta
A alpha
how can we assess whether a nerve fibres have been blocked or not
different nerve fibres have different functions so can assess if worked effectively
myelination status of A alpha
myelinated
myelination status of A beta
myelinated
myelination status of A gamma
myelinated
myelination status of A delta
myelinated
myelination status of C fibres
unmyelinated
function of A alpha fibres
sensory (proprioception)
motor (skeletal muscle)
function of A beta fibres
sensory (mechanoreceptors)
function of A gamma fibres
motor (muscle spindles)
function of A delta fibres
sensory (mechano-, themo-, noci- and chemoreceptor)
function of C fibres
sensory (noci-, thermo- and chemoreceptors)
autonomic (post ganglionic)
what function of C nerve fibres do you not want to anaesthetise
autonomic (post ganglionic)
mechanism of LA action
LA binds to a site in the Na+ channel
LA blocks the channel and prevents Na+ influx
- This blocks action potential generation and propagation
Block persists so long as a sufficient number of Na+ channels are blocked
- Enough blocked but not necessarily all
- Enough to avoid AP reaching maximum level
Local anaesthetics block Na+ channels in other excitable tissue, e.g. heart muscle
- LA can cause bradycardia and hypotension
Distressing for pt
- could faint
what group of nerve fibres are you aiming to anaethetise
A beta (3rd in order)
sensory (mechanoreceptors)
what class of molecule is LA
organic
what are the 3 basic components of LA
aromatic ring (hydrophobic)
ester or amide bond
basic amide side chain (hydrophilic)
what is evidence that the amine base in more water soluble than the chloride?
the LA is presented as a hydrochloride (B.HCl)
what is the active form of LA
B.H+
partially dissociated
what is the diffusible form of LA
B (inactive)
cannot cross membrane in active B.H+ form
what form of LA renders and block sodium channels in nerve
B.H+
how many B.H+ active molecules are needed to deactivate each sodium channel
one per channel
why are small diameter axons more susceptible to LA block
more channels are blocked proportionally
- less number of total channels
what is the distribution of sodium channels like in myelinated nerves
greater concentration at nodes of Ranvier
- more channels to block
is anaethetism by LA a linear process
no
what is the ‘safety factor’ of myelinated nerves
The local currents are strong enough to flow past the blocked region, and to regenerate the AP at the next node of Ranvier
- Block one node of ranvier
- Not able to block nerve or that axon
- Can bypass that LA block
Need to block a greater area
Need to dissolve to greater extent to anaesthetised axons that are myelinated
To block the AP, the LA needs to act on several nodes of Ranvier along the axon
what must the LA do in order to be effective on a myelinated nerve
Need to dissolve to greater extent to anaesthetised axons that are myelinated
To block the AP, the LA needs to act on several nodes of Ranvier along the axon
what is the role of the LA base present as hydrochloride in LA preparations
needed to increase solubility in aqueous solutions
what is the % range for dental preparations of LA
2-4%
what is the cartridge volume for dentistry LA use in UK
1.8 or 2.2ml
what is a common reducing agent in LA
sodium metabisulphide
4 basic constituents of LA preparations for dental use
LA base as hydrochloride
reducing agent (sodium metabisulphide)
preservative(s) and fungicide
and/or vasoconstrictor
what is the role of vasoconstrictor in LA preparations
prolong effect of aesthetic
- More time in certain area
- less LA volume needed
thus
- Reduce clearance
- Reduce need for larger volume
2 disadvantages of adding a vasoconstrictor
increase HR
Reduces the blood flow - needed in certain treatments
- Periodontal treatment - recreate healthy tissue (flap - stick gingiva from other area over)
Need to consider if affected by vasoconstrictor
- Tissue may not survive
what is the more likely cause of pt being allergic to LA
they are allergic to brand of LA
Preservative and reducing agent (preservative vary brand to brand, reducing less so)
E.g. Latex glaze on plug - common allergy
what should you do if you recognise that a pt is having an allergic reaction to a LA
note the product and manufacturer
both need to be ID to work out true cause of reaction
- rare to react to lidocaine
2 families of LA
esters
amides
3 ester LAs
benzocaine
(cocaine)
(procaine)
use of benzocaine
ester LA
Topical anaesthetic reduce pain but sting
Taste unpleasant
Varies between clinicians whether to use
- Technique can reduce need for topical
use of cocaine as LA
ester LA
good topical LA
hard to use
use of procaine as LA
ester LA
has toxic effects
6 amide LAs
ligocaine (lidocaine)
prilocaine
articaine
bupivacaine
(mepivacaine)
(ropivacaine)
what is a commonly used LA
ligocaine (lidocaine)
amide LA
common action of LA on circulation
most LAs are vasodilators
what is the effect of increased blood flow on the action of LA
increase ‘wash-out’
what can be added to LA to increase their duration of action
a vasoconstrictor
e.g. adrenaline, felypressin (synthetic vasopressin, for prilocaine)
what do vasoconstrictors act on
receptors in vascular smooth muscle
adrenoreceptors - alpha - beta 2 - beta 1 ADH receptors
in general what is the effect of vasoconstrictors
heart rate and force increased
alpha adrenoreceptor vasoconstrictor effect
vasoconstriction
beta 2 adrenoreceptor vasoconstrictor effect
vasodilation
beta 1 adrenoreceptor vasoconstrictor effect
on cardiac muscle
- positive chronotropic effect (increase rate)
- positive inotropic effect (increase force)
effect of adrenaline as a vasoconstrictor
Adrenaline is equally effective on alpha and beta receptors equal effect
- not preferential
Given locally, it has a vasoconstrictor effect (action on alpha receptors)
Systemically, it lowers TPR (beta > alpha - works on beta-2 more than alpha)
increases Cardiac Output
Overall, adrenaline has little or no effect on mean arterial BP
- More force and flow and less peripheral resistance
increase in HR and force gives feelings of palpitations
effect of noradrenaline as a vasoconstrictor
More effective on alpha than beta receptors
Given locally, it has a vasoconstrictor effect (alpha receptors)
Systemically, it increases TPR (alpha > beta)
- Effect lesser on beta
- So increase in arterial BP
increases Cardiac Output
Overall, NA raises mean arterial BP
- can cause a FALL of BP –Response of body when have increase in BP us not necessary or physiological
- Drive blood flow to other areas
- Reduce peripheral resistance
Can overshoot if go too high can cause fall in BP (overshoot)
what is a possible side effect of noradrenaline as a vasoconstrictor
Overall, NA raises mean arterial BP
- can cause a FALL of BP –Response of body when have increase in BP us not necessary or physiological
- Drive blood flow to other areas
- Reduce peripheral resistance
Can overshoot if go too high can cause fall in BP (overshoot)
what process occurs to inactivate LA
Washout’ from tissues by blood supply
Countered by presence of vasoconstrictor agent
how are ester LAs broken down
by tissue esterases
in general what is the duration of action of ester LAs
action is quite brief
topical anaesthetic
how are amide LAs broken down
by liver amidases
in general what is the duration of action of amide LAs
longer duration of action
6 modes of LA administration
Surface application (‘topical’)
Injection
Local infiltration
Regional nerve block
Nerve root block (‘spinal’, ‘epidural’)
Intravenous
why is it important to ask about pt liver medical history
amide LAs are broken down by liver amidases
re-evaluate how to use LA as process of removal is effected
what type of nerve blocks do dentists use
local nerve blocks
- ID nerve block
rare to use root nerve blocks (maxillofacial)
2 common drugs used for LA preparations in dentistry
ligocaine
prilocaine
common LA dental preparation of ligocaine
2% ligocaine HCl
2% ligocaine HCl and 1:80,000 adrenaline
common LA dental preparation of prilocaine
4% prilocaine HCl
3% prilocaine HCl + felypressin (0.03Uml)
why would there need to be a higher concentration of prilocaine in LA preparation without a vasoconstrictor
reduced clearance with vasoconstrictor hence lesser volume required
% solution =
X mass/volume
e.g.
3% Prilocaine HCl solution
- 3% = 3g / 100ml
- = 30mg / 1ml
A 2ml cartridge of 3% prilocaine HCl will contain
2 x 30 = 60mg prilocaine HCl
In clinic 2.2 calculate
1ml=
1g
how are vasoconstrictors volumes given for LAs
very small volumes are present
content is expressed as a ratio:
e. g. 1:80,000
- 1 part of adrenaline in 80,000 parts of liquid
maximum dose of ligocaine
4mg per kg body weight
Reach max dose of LA first before adrenaline
- But symptoms tend to be more associated with adrenaline
Although bradycardia is serious
maximum dose adrenaline
500 micrograms (ug)
Cartridge contains 27.5 ug adrenaline
- If this entire amount was injected into 5 litres of blood then 5ug/l
Plasma levels of adrenaline following dental injections increase with amount injected
- Increase in force and speed of heat
The plasma levels following ‘normal’ injections are within the physiological range (up to 0.5 ug /litre) *
- Not inject BV – entering blood stream
Maximum physiological levels (intense exercise) can reach 0.5 ug /litre
Reach max dose of LA first before adrenaline
- But symptoms tend to be more associated with adrenaline
Although bradycardia is serious
