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
