Local Anaesthetics Flashcards
Describe the mechanism of action of LA
Stops axonal conduction by blocking sodium channels in axonal membrane when applied at appropriate concentrations
Sodium ion entry prevented, slow down/ halt conduction
Factors affecting LA action
Lipophilicity
Size of nerve small> large
Frequency of firing greater frequency, greater LA effect
Position circumferential > deep
Myelination myelinated> non myelinated
pH dependency (less ionised, tissue cannot be inflammed)
What kind of LA has the fastest onset of action?
Lipophilic, small, lowly ionised LA as can penetrate nerve sheath and axon membrane to reach inner Na channel
Name more lipophilic LAs
tetracaine, etidocaine, bupivacaine
Name less lipophilic LAs
lidocaine, procaine, mepicaine
Name the LAs that are esters
Procaine, cocaine, tetracaine, benzocaine
Name the LAs that are amides
Lidocaine, etidocaine, mepivacaine, bupivacaine, prilocaine, ropivacaine
Metabolism of esters vs amides
esters metabolised in blood by esterases
amides metabolised in liver by hepatic enzymes
Why LAs that are esters have higher incidence of allergy reactions?
Esters are hydrolysed into p-aminobenzoic acid (PABA) derivatives which some people might be allergic to
Why higher action potential frequency results in greater nerve block?
More access to sodium channel is gained when it is open (activated)
Higher affinity to inactivated sodium channel than closed
How selective are LAs?
Non-selective modifiers of neuronal function so block action potentials in ALL neurons
Hence u gotta deliver it to a LIMITED area
How to choose which LA to use?
Based on duration of action
If u have PABA allergy use AMIDES
If u have liver problems use ESTERS
If you need surface
Fun fact: cocaine has good penetration of skin and cause vasoconstriction as blocks Na reuptake so can be used as surface anesthesia (rapid penetration, limited diffusion)
Systemic distribution of LAs
Steep exponential decline in [LA], rapid distribution in blood and highly perfused organs
Slower decline in [LA] (linear), distribution to less well perfused organs
Toxicity occurs when…
How to prevent toxicity?
Unintended large dose of LA administered IA/ IV can lead to systemic toxicity
Excessive LA injected locally lead to high and toxic blood levels following absorption
Can combine with epinephrine to prevent SD from site of action as it causes vasoconstriction that reduces blood flow to other areas
List possible toxic effects of specific LAs
Bupivacaine more cardiotoxic
Prilocaine metabolised into O-toluidine which causes methaemoglobin which means rbcs cannot transport O2 (bluish blood)
