LA symposium 2 - Local anaesthetics Flashcards
How do local anaesthetics stop nerve conduction
by blocking voltage-gated Na channels
which receptor in the nerve pathway does LA work on
first order afferent receptor (we don’t interfere with CNS)
Why will the nerve axon closest to the LA injection site be the first to be anaesthetised
it’s closer and the number of membranes that it has to cross is the same as axons further in the bundle
what very important characteristic does LA need to be to cross membranes in peripheral nerves
lipophilic
what impact does fat within the peripheral nerve have on the LA
allows it to stay longer
Nerve axons differ in their susceptibility to block by LA, what is the order that the fibres block in
- A delta
- C
- A beta
- A alpha
Why might a dentist tell a patient the tooth will be numb but you might feel pressure
- because nerve axons differ in their susceptibility to block by LA
- A alpha fibres blocked last are involved in proprioception
What are the functions of the different types of nerve axon
A alpha
- sensory (proprioception)
- motor (skeletal muscle)
A beta
- sensory (mechanoreception)
A gamma
- motor (muscle spindles)
A delta
- sensory (mechano-, thermo- noci- and chemo-receptors)
C
- sensory (noci-, thermo- and chemo- receptors)
- autonomic (post-ganglionic)
What is the mechanism of action of LA
- LA binds to a site in the Na channel
- LA blocks the channel and prevents Na+ influx
- this blocks AP generation and propagation
- block persists so long as a sufficient number of Na channels are blocked
what effect does LA have on the heart and why
- can cause bradycardia and hypotension
- LA block Na channels in other excitable tissue e.g. heart muscle
what are the components of LA
3 components:
- aromatic region (hydrophobic)
- ester or amide bond
- basic amine side chain (hydrophilic)
Why are LA’s presented as hydrochloride (B.HCl)
renders the amine base more water soluble (so increases solubility)
What form do LA’s have to be to cross the membrane
partly dissociated
- active in ionised form
- can cross membrane only in un-ionised form
Why are small diameter axons more susceptible to LA block
because of number of channels which are blocked. Small diameter axon has less channels to block
How do myelinated axons impact susceptibility to LA
- more channels to block
- Na+ channels (and K+ channels) are concentrated at the nodes of ranvier
- so need safety factor
why do we need safety factor
- on myelinated axons the local currents are strong enough to flow past the blocked region, and to regenerate the AP at the next node of ranvier
- to block the AP, the LA needs to act on several nodes of ranvier along the axon
How should LAs be prepared
- LA base present as hydrochloride, to increase solubility in aqueous solution
- for dental injections, 2-4% solutions
- reducing agent (sodium metabisulphide)
- preservative(s) and fungicide
- +/- vasoconstrictor
When people say they are allergic to LA what do they usually mean
- that it’s the preservative/ reducing agent that they are allergic to
- check manufacturer
- possible but rare to be allergic to the actual LA
what are the 2 types of LA
- esters
- amides
What is the ester that we normally use
Benzocaine (topical LA)
What amides do we use
- Lignocaine (lidocaine)
- prilocaine
- articaine
- bupivacaine (surgical procedures)
Why are vasoconstrictors added to most LAs
- most LAs are vasodilators
- increased blood flow will increase ‘wash-out’ of LA
- to increase duration of action, LA preparations often include a vaso-constrictor
what are used as vasoconstrictors
- adrenaline
- felypressin (synthetic vasopressin)
What do vasoconstrictors act on
receptors on vascular smooth muscle
- adrenoreceptors (alpha and beta)
- ADH receptors (vasopressin)
What effect does adrenaline have as a vasoconstrictor
- EQUALLY effective on alpha and beta receptors
- given locally, it has a vasoconstrictor effect (alpha receptors)
- systemically, it LOWERS TPR (as beta more than alpha)
- increases cardiac output
- has little or no effect on mean arterial bp
- more force, more flow, less peripheral resistance
what effect does NA have as a vasoconstrictor
- NA is MORE effective on alpha than on beta receptors
- given locally, it has a vasoconstrictor effect (alpha receptors)
- systemically it INCREASES TPR (alpha more than beta)
- NA increases cardiac output
- overall raises mean arterial BP
- BUT this can result in a fall of bp…
why does the fact that NA raises mean arterial blood pressure actually potentially result in a fall in blood pressure
response of body that isn’t necessary is trying to compensate and reduce peripheral resistance - compensation overshoot
How is LA inactivated
- washout from tissues by blood supply
- countered by presence of vasoconstrictor agent
- ester types broken down by tissue esterases (action brief)
- amide types broken down by liver amidases (action longer duration)
What are the different modes of administration of LA
- surface application (‘topical’)
- injection
- local infiltration
- regional nerve block
- nerve root block (‘spinal’, ‘epidural’)
- intravenous
What are the LA preparations for dental injections
Lignocaine
- 2% lignocaine HCl
- 2% lignocaine HCl + 1:80,000 adrenaline
Prilocaine
- 4% prilocaine HCl
- 3% prilocaine HCl + felypressin (0.03U/ml)
How do you work out what a solution should contain from percentages
X% 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
why are vasoconstrictors given as a ratio rather than a percentage
because very small amounts of vasoconstrictor are present in LA preparations
e.g. rather than <0.001%, 1:80,000 (same for fluoride concentrations)
what is the max dose of lignocaine
approx 4mg per kg body weight
what is the max dose of adrenaline
500µg (BNF)
how much adrenaline does a cartridge contain
27.5µg
- if this entire amount was injected into 5 litres of blood –> 5µg/l
- plasma levels of adrenaline following dental injections increase with amount injected
- the plasma levels following ‘normal’ injections are within the physiological range (up to 0.5µg/litre)
- max physiological levels (intense exercise) can reach 0.5µg/litre
