Local Anaesthetics Flashcards
Give examples for amide-containing local anaesthetics and describe them
- Lidocaine/Lignocaine - medium-acting, rapid onset
- Prilocaine - medium-acting, no vasodilation
- Bupivacaine/Levobupivacaine - long-acting, slow onset
- Articaine - short-acting, rapid onset
Give examples for ester-containing local anaesthetics and describe them
- Tetracaine - long-acting, very slow onset
- Chloroprocaine - medium-acting
- Benzocaine - atypical mechanism of action
Difference between ester-containing and amide-containing local anaesthetics
Ester-containing
- unstable
- easily hydrolysed by enzymes (e.g.: duration of action of Procaine depends on action of plasma esterases)
- the breakdown products can cause allergic reactions
Amide-containing
- more stable
- doesn’t break down aka less chance of inducing allergic reactions
- longer duration of action
- metabolised in liver in a controlled process
What is a local anaesthetic molecule made up of?
- Aromatic region (aka they are hydrophobic/lipophilic)
- Ester/amide bond
- Basic amine side chain that can become protonated/charged
What do we lose and in what order after being treated by local anaesthetics?
- Pain
- Temperature
- Proprioception (unconscious perception of movement)
- Skeletal muscle tone
What factors determine the sensitivity of fibres to local anaesthetics?
- Diameter of fibres - smaller nerve fibres get blocked more easily since less voltage gated Na+ channels on their walls
- Myelination status - myelinated fibres get blocked more easily since less “holes” on axon aka less voltage gated Na+ channels
- Length of nerve exposed to drug
- Length of time exposed to drug
- Concentration of drug
What is the Henderson-Hasselbalch weak base equation?
What is it used for?
pKa - pH = log10( [BH+]/[B] )
Used to calculate the proportion of ionised and deionised drugs
What is the pKa value?
The pH at which 50% of the molecule is disassociated/drug is ionised
aka: if we place LA of pKa of 8 into pH8, we would get 50-50%
Most LAs have a pKa of 8 or 9
How do local anaesthetics block the voltage gated Na+ channels?
Local anaesthetics cross the membrane unionised/uncharged and then they can either:
- pass through the lipids and get to the v.g. Na+ channels without opening the channels (hydrophobic pathway; no use-dependence), where they block them
- get to the cytoplasm and enter the v.g. Na+ channels by opening them (hydrophilic pathway; use-dependence), and block them
What is the duration of action of local anaesthetics dependent on?
- Blood flow
- Action of plasma esterases (in ester-linked LAs only)
- Hydrophobicity of drug
What is the onset of the local anaesthetics dependent on?
Since many LAs show use-dependence, they bind to the channels to open them
- there is a faster onset on faster firing neurons
How can the duration of action of local anaesthetics be increased?
Decreasing rate of removal
- decreased blood flow (so washed away slower)
- vasoconstriction (adrenaline) - ischaemic damage at extremities though
What are the routes of administration of local anaesthetics?
- Surface (nose, mouth)
- Infiltration (injection into tissues to reach nerve branches)
- Nerve block (injection around nerve)
- Intravenous regional (double-cuff method to contain LA to limb)
- Subarachnoid (into CSF)
- Extradural (mostly Bupivacaine; in thoracic, lumbar, sacral regions)
What is EMLA (Eutectic Mixture of Local Anesthetics)?
- Mixture of lignocaine and prilocaine, used for dermal anaesthesia; very low melting point
- Takes 30-40 minutes
Possible side effects of local anaesthesia
Cardiovascular system
- Dysrhythmias
- Sudden fall in blood pressure
CNS
- Restlessness
- Tremors
- Convulsions
- Respiratory centre depression
- Death
