Lecture 32: Local Anaesthetics Flashcards
Describe the conceptual operation of the voltage gated Na channel:
RMP
Threshold: With inner and outer gates open, Na influxes
Automatic deactivation: Inner gate closes
Recovering: Outer gate closes, inner gate opens, Back to RMP status
Describe the basic ion flow of neural cell depolarisation:
Na influxes and threshold is reached. All Na channels open and cell depolarizes. K channels open, K effluxes and cell repolarizes.
How do local anaesthetics work?
Local anaesthetic molecules block the Na channel, prevent voltage dependent increase in Na ion conductance.
What is the structure of local anaesthetic molecules?
Aromatic group (Hydrophobic)
Amide or ester link
Amine (HYdrophilic)
What is the structure activity relationship?
Ester or amide bonds determine site of metabolism and potential to produce allergic reactions
Esters are more rapidly metabolized (and shorter acting) and more allergenic.
What are the important esters (LA)?
Cocaine
Procaine
Benzocaine
Tetracaine
What are the important amides (LA)?
Prilocaine
Most commonly used LA:
Lignocaine
Bupivocaine
Ropivacaine
Describe the relationship between acid base status and LA activity:
ALL LOCAL ANAESTHETICS ARE WEAK BASES
- ONLY FREE BASES (non ionised) CAN CROSS MEMBRANES
Therefore, the amount of free base present at physiological pH depends on the pKa of the drug.
More free base = faster onset of action
High pKa vs low pKa, what is better?
High pKa = Ionized from
Low pKa = Free based, i.e faster diffusion, ie quicker onset
Order the 7 common La in rank of onset speed:
Slower i.e higher pKa:
Procaine Tetracaine Bupivacaine Ropivacaine Prilocaine Lignocaine
Faster i.e lower pKa
Explain why La arent effective as a block in acidic infected tissue
LAs with pKa closest to physiological pH have fastest onset of action
This explains poor quality of block when LA injected into acidic infected tissue.
What increases the solubility of LAs? Rank 4
Lengthening alkyl chain increases lipid solubility. In general: More lipid soluble = more potent
Most lipid soluble: Bupivicaine Lignocaine Prilocaine Procaine Least:
What influences the duration of LA? Rank 4:
Protein binding, the more protein binding the more duration of action
Most: Bupivicaine Ropivacaine Lignocaine Prilocaine Least:
What breaks down LA?
Esters: Plasma cholinesterases
Amides (And some cocaine): Liver metabolism
Write some notes on Lignocaine/Lidocaine:
AMIDE (standard agent to which others compared)
Potency -> Low lipid solubility, Low potency
Onset -> Lower pKa, non-ionised, FAST ONSET
Duration -> Low protein binding, Short Duration of action
Ideal for short surgical procedures i.e dental or mole removal
Write some notes on bupivocaine:
AMIDE
Potency -> High lipid solubility, More potent that ligno
Onset -> High pKa, slower onset that ligno
Duration -> High protein binding, Longer Duration of action that ligno
Ideal for nerve blocks for prolonged anaesthesia (peripheral nerve block)
Write some notes on cocaine:
Ester, topical to nose, vasoconstrictor
Write some notes on prilocaine:
Amide, SAFEST agent, used in IV regional anaesthesia (Lowest CV toxicity)
Write some notes on Ropivacaine:
Amide, slow onset, long acting like bupivacaine, but less cardiac toxicity.
How can LA be toxic?
- Allergic reactions (rare amides)
- Dose dependent CNS toxicity i.e seizures, tinnitus
- Dose dependent CV toxicity i.e heart block, Vfib, both more likely and dangerous with bupivacaine
- CC-CNS ratio:ratio dose required to cause cardiac VS CNS toxicity i.e Lignocaine 7, bupivicaine 3 i.i.e Takes 3x the dose of bupivicaine to cause cardiac vs CNS toxicity
- Usually inadvertant IV administration
Write some notes of LA use topical to skin:
EMLA (Eutectic mixture of LAs)
- Mixture of lignocaine and prilocaine as an oil prep (more free base and can cross skin)
Write some notes of LA use topical to mucous membranes:
- Cocaine (also vasocon adv)
- Lignocaine spray and viscous preps (Instrumentation of the nose/mouth/pharynx/urethra
Write some notes on the soft tissue infiltration of LAs:
Soft tissue infiltration
- For minor interventions i.e mole removal (fast acting, short duration agent)
- For post operative pain relief in surgical wounds (Slow acting, long duration agent)
Where can a nerve block be placed?
- Peripheral NB
- Neuroaxial (spine) NB
Write some notes on a peripheral nerve block:
Peripheral nerve block
- LA is infiltrated around a specific nerve i.e brachial plexus for surgery on the arm
- A mixed nerve, smaller sensory more susceptible, but motor can be affected
- For surgery without GA, or post op pain releif
Write some notes on neuralaxial blockade specifically a spinal block:
Spinal anesthesia
- LA injected into the INTRATHECAL space (ONLY BELOW L2) where SC terminates
- Profound distal motor and sensory blockade
- i.e major surgery of knee, hip, C section IN AWAKE Pt
Write some notes on neuroaxial blockade specifically an epidural anaesthesia:
Epidural anesthesia
- Small catheter inserted into epidural space and LA infused. Bathes spinal nerves passing through space. can be done at any level
- Distal sensory +/- motor blockade
- Excellent post op or labor analgesia if inserted at correct level.
