Local Anaesthesia Flashcards
What is the difference between inactivation and deactivation of ion channels?
Inactivation - ion flow blocked by gating mechanism, not the closing of channel itself
Deactivation - ion flow blocked by closing of the channel
What is the MOA of LA?
Stop axonal conduction by blocking sodium channels in the axonal membrane, when applied locally in appropriate concentration -> prevent sodium ion entry -> slow down or bring conduction to a halt
When does LA bind most strongly to the channel?
LAs bind most strongly to the inactivated and activated states.
What is the use dependency of LAs?
The depth of LA nerve block increases with action potential frequency bc LA molecules gain access to the sodium channel more readily when the channel is open and have higher affinity for the inactivated than for the resting (closed) channels
Are LAs selective?
No, LAs are non selective modifiers of neuronal function. They block action potentials in all neurons to which they have access. Hence, we deliver LAs to a limited area.
What are the factors affecting LA action?
- more lipid soluble drugs are more potent and act longer. the more hydrophobic drugs are: tetracaine, etidocaine and bupivacaine. the less hydrophobic drugs are: lidocaine, procaine and mepivacaine.
- size: smaller nerve > bigger nerve
- myelination: myelinated > non-myelinated
- frequency of firing: high (sensory) > low (motor)
- position: circumferential > deep
hence, small, myelinated axons > small, non-myelinated axons > large, myelinated axons (SIZE MORE IMPT THAN MYELINATION)
nociceptive and sympathetic transmission is blocked first bc they are small and myelinated.
- pH dependency: LA molecules are weak bases, mainly ionized at physiological pH. Alkaline pH -> increased LA activity bc proportion of ionized molecules is low. Acidic pH (like in inflammation) -> decreased LA activity bc proportion of ionized molecules is high -> cannot pass through membrane to reach intracellular part of sodium channel.
What are the four ester LAs?
Cocaine, procaine, tetracaine and benzocaine.
Procaine: Short acting
tetracaine: long acting
What are the three amide LAs?
Lidocaine (medium acting), mepivacaine (medium acting), bupivacaine (long acting)
How are ester LAs metabolized?
Plasma/tissue non-specific esterases
How are amide LAs metabolized?
Hepatic enzymes. Hence, don’t use amide LAs in hepatic disease.
What determines how much LA gets into the blood?
LAs mostly have local action. Blood flow to the site of administration determines how much gets absorbed into the blood.
What is the toxicity of LAs?
Toxicity occurs when unintended large doses of LA is accidentally injected IV/intra-arterial -> systemic toxicity.
Or if excessive (overdose) of LA is injected locally and subsequently high levels in blood following absorption -> onset of toxic signs and symptoms may appear late.
What can you combine LAs with?
Can combine LA with epinephrine to prevent LA systemic distribution from the site of action. (epinephrine causes vasoconstriction and hence reduces blood flow)
What are the two types of LA toxicity?
CNS toxicity and CVS toxicity (both contain a lot of sodium channels).
Both of which can lead to death.
Bupivacaine is more cardiotoxic than most other LAs.
Cocaine blocks NA reuptake, increased NA causes vasoconstriction and hypertension.
How can LA lead to methaemoglobin?
O-toluidine (metabolite of prilocaine) causes methaemoglobin (haemoglobin becomes dysfunctional).
Use IV methyleneblue/ascorbic acid to convert methaemoglobin to haemoglobin.
