LA Flashcards
Types of local anaesthetics (2)
- Esters
- Procaine
- Tetracaine - Amides
- Lidocaine
- Mepivacaine
- Bupivacaine (cardiotoxicity)
Stages of voltage-gated Na+ channels (4)
- Closed
- Activated
- Inactivated
- Deactivated
Inactivated vs Deactivated Na+ channels
Inactivated
- channel open
- gate closed
Deactivated
- channel closed
- gate closed
MOA of LA
- block Na+ channel in axonal membrane intracellularly
- at appropriate dose
- locally
(( prevent depolarisation ))
Use-dependency
Depth of LA nerve block increases with action potential frequency (increase transition between the various stages of channel) cos
- gain access to the channel more readily when channel is open
- have higher affinity for inactivated than closed channels
hence, increasing pain, frequency of action potential increases, increasing LA action
Selectivity of LA
- non-selective
Methods to minimise systemic absorption of LA
- Apply locally to minimise blocking of action potentials in all neurons
- Use of epinephrine to constrict blood vessels
Factors affecting LA actions (6)
- Size (small > large)
- Myelination
- Frequency of firing : high(sensory) > low(motor)
- Position of nerve (circumferential > deep)
- pH (intracellularly & extracellularly)
eg inflammation - Lipid solubility of LA
Types of nerve fibres
Type A - least sensitive to LA block - but most myelinated Type B - most sensitive to LA block - smaller size Type C - most sensitive to LA block - smallest size
Why pH can affect LA action?
- LA pKa 8-9 (weak bases)
- at low pH, LA ionised to positively charged, reduce amount available to cross membrane
- LA bind intracellularly to block Na+ channels
pH and LA relationship
Low pH (acidic) - low activity High pH (alkaline) - high activity
How LA causes anaesthesia?
- Unionised LA passes through lipophilic membrane intracellularly
- Ionisation of LA
- Binding of LA to the inner end of the sodium channel (activated/inactivated)
Esters LA (2)
- Procaine
- short acting - Tetracaine
- long acting
Amides LA (3)
- Lidocaine
- moderate acting - Mepivacaine
- moderate acting - Bupivacaine
- long acting
Incidence of LA allergies (esters vs amides)
Esters
- low
- due to metabolism to p-aminobezoic acid (PABA)
Amide
- very low
Metabolism of LA (esters vs amides)
Esters
- plasma/tissue non-specific esterase
Amide
- hepatic enzymes
Distribution phases of LA
2.
Phase l - highly perfused tissues
- steep decline
- heart, liver, kidney, lungs
Phase ll - less perfused tissues
- less steep, assume nearly linear
- GI, muscles
Causes of LA toxicity (2)
- Incidental administration of LA IV/intra-arterial
- Overdosage lead to systemic absorption
Hence, combine with epinephrine to prevent systemic distribution of LA from site of action
LA toxicity (4)
- bupivacaine (cardiotoxicity)
- cocaine (constricts blood vessels -> hypertension)
- o-toluidine (metabolite of prilocaine, causes methaemoglobin)
- esters LA (metabolised to p-aminobenzoic acid which trigger allergies)
Methods of local anaesthesia
- Surface anaesthesia (not for skin)
- Infiltration anaesthesia
- Nerve-block anaesthesia (close to nerve trunks)
- Epidural anaesthesia (epidural space)
Choice of LA (2)
- Duration of action
2. Site of action
Patients with liver dysfunction
Esters LA
- cannot give amide LA cos it decrease metabolism, increase duration of action
Patients with PABA allergies
Amide LA
- very low chance of triggering allergy
Treatment for Methaemaglobin
IV methylene blue or ascorbic acid
Lipid solubility of LA
More hydrophobic (TEB)
- Tetracaine
- Etidocaine
- Bupivacaine
Less hydrophobic (LPM)
- Lidocaine
- Procaine
- Mepivacaine
High frequency of activation of action potentials
Sensory neurons
Low frequency of activation of action potentials
Motor neurons
How does lipid solubility of LA affects its action?
Increase lipid solubility increase LA action
- permeation through membrane
- permeation through myelin sheath
How does application of LA on inflamed wound affect its action?
Inflammation
- more acidic extracellularly
- more positive ionisation of LA
- decrease permeation across membrane
- decrease LA blocking of Na+ channels intracellularly
Hierarchy of the factors affecting LA action
size vs myelination
size > myelination
small myelinated > small non-myelinated > large myelinated
What kind of transmission is blocked first? (2)
- Nociceptive transmission
- Sympathetic transmission
Why is pH important in affecting LA action?
pH plays a critical role in LA penetration of nerve sheath and axon membrane to reach inner end of the Na+ channels (which is LA binding site)
Hence, LA action is strongly dependent on pH
pKa of LA
pKa 8-9 (weak bases)
- mainly ionised (but not completely) at physiological pH of 7.4
