Lecture 12: local anaesthetics Flashcards
General mechanism of action of local anaesthetics?
They become non-ionized and travel into the neuron before becoming re-ionized where they block Na+ channels on membranes from the inside stopping AP travelling.
General structure of local anaesthetics and the implications of this?
Ester bond or amide bond between an aromatic and a amine group
The ester bonds are more rapidly metabolised (shorter acting) and more likely to give an allergic reaction - not used as much these days
Structure-activity relationship?
They are all weak bases so exist in an ionized and non-ionized (free base) and this ratio is determined by pKa of the drug. A low pKa will therefore have more free base so work faster.
Lengthening the alkyl chain also increases their lipid solubilty so they are more potent.
Explain why anaesthetics injected into infected areas are less fast acting?
Because the infected area is acidic and so the pH is lower and thus further away from the pKa of the weak base anaesthetic leading to less free base being available.
What does duration of action vary with?
Protein binding
Lignocaine structure, properties, ideal use?
- Amide
- Low lipid solubility = low potency
- low pKa = fast onset
- low protein binding = short duration
- ideal to cover short surgical procedures (eg. dental or mole removal)
Bupivacaine structure, properties and ideal use?
- Amide
- High lipid solubility = more potent
- High pKa = slower acting
- High protein binding = Longer duration of action
- Ideal for nerve blocks for analgesia
3 other alternative anaesthetics?
Cocaine - ester, topical to nose, vasoconstricts
Prilocaine - Amide, very safe, IV regional anaesthesia -(using cuff = Bier’s block)
Roprivocaine - Amide, slow onset, long acting, low cardiac toxicity
LA toxicity?
- Allergic reactions - very rare with amides
- Dose dependent CNS toxicity -(seizure)
- Dose dependent cardiac toxicity -(cardiac arrest)
- Dose dependent toxicity from accidental IV administration but can be just too much in tissue.
CC:CNS ratio is how much you have to give to induce a cardiac arrest vs a seizure. A bigger number the best chance of not messing up accidentally. If someone has a seizure then STOP.
topical administrtion and uses of LAs?
-
Topical to skin
- EMLA - eutectic mixture of LAs
- Mixture of lignocaine and prilocaine in an oil to allow it all to be free base.
- used for insertion of IV cannulae to children. - Topical to mucus membranes
- Cocaine
- lignocaine spray and viscous preparations for nose/mouth/pharynx/urethra
soft tissue administration and use?
- for minor interventions like mole removal they are fast acting and short lasting
- For post opertative pain relief around the wound
types of nerve blocks?
- Peripheral nerve block
- Neuraxial blockade
Peripheral nerve block?
LA is infiltrated around a specific nerve
Sensory fibres more susceptable but motor fibres can be affected as well
Good for surgery without GA or for post-op pain
Neuraxial blockades?
-
Spinal Anaesthesia
- LA is injested onto the intrathecal space below L2
- Profound distal motor and sensory blockade from level down -
Epidural anaesthesia
- Small catheter inserted into epidural space using loss of resistance technique
- creates a band on numbness at that spinal level for up to 2/3 days if catheter is left in and continual anaesthetic release.