Local Anesthetics Flashcards
What is the mechanism of action of LA?
Stop axonal conduction by blocking sodium channels in axonal membrane when applied locally in appropriate concentration -> prevent sodium ion entry -> slow down or bring conduction to halt
Which type of voltage-gated sodium channels do LA mostly bind strongly to?
Inactivated and Activated states
Why does depth of LA nerve block increase with action potential frequency?
LA molecules gain access to channel more readily when channel is open and has higher affinity for inactivated than resting channels
How to achieve selectivity for LAs?
Deliver LA to limited area (most LAs are topical and not in pill form)
What are some factors the affect LA action?
- Lipid solubility - more lipid soluble more potent and act longer
- Size - smaller nerves>bigger nerves
- Frequency of firing - high (sensory)>low (motor)
- Position - circumferential>deep (large nerve trunk)
- Myelination - myelinated>nonmyelinated
- pH dependency - alkaline (low proportion of ionised molecules)>acidic
Example of ester-type
Procaine, cocaine, tetracaine, benzocaine
Example of amide-type
Lidocaine, mepivacaine, bupivacaine
What is the method of metabolism for ester-type LA?
Plasma/tissue non-specific esterases
What is the method of metabolism for amide-type LA?
Hepatic enzymes
What happens in phase I of systemic distribution?
Steep exponential decline in [LA] and rapid distribution in blood and highly perfused organs
What happens in phase II of systemic distribution?
Slower decline in [LA] and distribution to less well perfused tissue
What can unintended large dose of LA lead to?
Systemic toxicity
What can LA combine with to prevent LA systemic distribution from site of action?
Epinephrine
Which LA is more cardiotoxic?
Bupivacaine
Toxic effects of cocaine
Blocks NA reuptake -> increased NA causes vasoconstriction and hypertension
Toxic effects of O-toluidine (metabolite of prilocaine)
Methaemoglobin (iv methyleneblue/ascorbic acid methaemoglobin to haemoglobin)
What does hydrolysis of ester LAs lead to?
Ester LAs hydrolysed to PABA -> allergic reaction in small percentage of population
2 ways of injected LAs
- Epidural anaesthetics (Lidocaine, bupivacaine)
-Regional nerve block - Dental anaesthesia (Lidocaine - short time, bupivacaine - long time)
5 ways of topical LAs
- Skin
-minor burns/inflamed/wounds - Eye
-remove foreign objects - Dental
-applied to gum due to entry of injection needle - Otorhinolaryngology
-insertion of endoscope for gastric ulcer scope - Gynaecology (Lidocaine)
-episiotomy cuts
What affects choice of drug?
-Duration of action
-Surface requires rapid penetration of skin and limited tendency to diffuse away
What is the clinical use of cocaine?
Good penetration and vasoconstriction -> most often used for ENT procedures
Difference between ester-type and amide-type LAs
- Ester type occasionally cause allergic reaction but amide-type rarely cause allergic reaction
- Ester-type is inactivated by blood esterases but amide-type is inactivated by liver enzymes
