Local Anaesthetic Flashcards
How do local anaesthetics stop nerve conduction?
Blocking of voltage-gated Na+ channels
Nerve axons differ in their susceptibility to block by LA, list the order of block of different nerve fibres
- A delta
- C
- A beta
- A alpha
Describe the mechanism by which sodium channels are blocked by LA and how this affects the nerve
- LA binds to a site in the sodium 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
What other areas can LA effect and what problems can this cause?
- LA block Na+ channels in other excitable tissue (e.g. heart muscle)
- LA can cause bradycardia and hypotension
What are the 3 organic components are present in LA?
- Aromatic region (hydrophobic)
- Ester or almond bond
- Basic amine side chain (hydrophilic)
How are LA presented and why is this useful?
Presented as hydrochloride (B.HCL)
- renders the amine base more water soluble
When can LA cross the cell membrane?
Only in un-ionised form
When are LA active?
When they are ionised
Why are LA much less effective on acidic tissues?
Dissociation of B.H+ will not act quickly due to the high number of H+ ions around the tissue. This makes it much more difficult for the LA to pass through the cell membrane
Why are smaller diameter axons more susceptible to LA block?
Because the number of sodium channels in smaller axons is less, therefore less LA is needed to block all sodium channels
Why are myelinated axons susceptible to LA?
Sodium channels (and potassium channels) are concentrated into the nodes of Ranvier
What is ‘safety factor’ in relation to LA?
To block AP in myelinated nerve fibres, the LA needs to act on several nodes of Ranvier along the axon - so more LA is used than in unmyelinated nerve fibres
Describe the composition of LA preparation
- LA base present as hydrochloride to increase solubility in aqueous solution
- 2-4% solutions for dental injections
- Reducing agent (sodium metabisulphide)
- Preservatives and fungicide
- Vasoconstrictor (+-)
What esters have been/are used as LA?
- Cocaine
- Procaine
- Benzocaine (used now)
What amides are used as LA?
- Lignocaine(lidocaine)
- Prilocaine
- Árticaine
- Mepivacaine
- Bupivacaine
- Ropivacaine
Why are vasoconstrictors important to include in LA preparations?
- Most LA are vaso dilators
- increased blood flow will increase ‘wash out’ of LA
- therefore a vasoconstrictor will increase duration of action
What vasoconstrictors are often used in LA?
Adrenaline
Felypressin (synthetic vasopressin)
Describe the adrenoreceptors that vasoconstrictors interact with
- Vasoconstrictors act on receptors on vascular smooth muscle
• adrenoreceptors:
- alpha receptors: vasoconstriction
- Beta 2 receptors: vasodilation
- Beta 1 receptors:
. In cardiac muscle have positive chronotropic and inotropic effect (increase heart rate and force)
How effective is adrenaline as a vasoconstrictor?
How does it effect blood pressure?
- Adrenaline is equally effective on alpha and beta receptors
- Given locally, it has a vasoconstrictor effect (action on Alpha receptors)
- Systemically, it lowers Total Peripheral resistance (B > a)
- Adrenaline increases cardiac output
- but overall has little to no effect on mean arterial blood pressure
How effective is noradrenaline as a vasoconstrictor?
How does it effect blood pressure?
- Noradrenaline is more effective on alpha than beta receptors
- given locally, it has a vasoconstrictor effect (alpha receptors)
2.
- systemically, it increases TPR (a>B)
- increases cardiac output
- therefore raises mean arterial BP
- this can result in a fall of BP
How are LAs inactivated?
- ‘Washout’ from tissues by blood supply
- Countered by presence of vasoconstrictor agent
- Ester types broken down by tissue esterases
- action quite brief - Amide types broken down by liver amidases
- longer duration of action
List different modes of administration for local anaesthetics
- Surface application (‘topical’)
- Injection
- Local infiltration
- Regional nerve block
- Nerve root block (‘spinal’, ‘epidural’)
- IV
List LA preparations for dental injections using lignocaine and prilocaine
- Lignocaine
- 2% lignocaine HCL
- 2% lignocaine HCL + 1:80,000 adrenaline - Prilocaine
- 4% prilocaine HCL
- 3% prilocaine HCL + felypressin (0.03U/ml)
How are percentage solutions calculated?
X% solution = Xmass/volume
What is the maximum dose of lignocaine?
4mg per kg of body weight
What is the maximum dose of adrenaline?
500micrograms
