Local Anesthetics

Question 1

What is the mechanism of action of LA?

Answer 1

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

Question 2

Which type of voltage-gated sodium channels do LA mostly bind strongly to?

Answer 2

Inactivated and Activated states

Question 3

Why does depth of LA nerve block increase with action potential frequency?

Answer 3

LA molecules gain access to channel more readily when channel is open and has higher affinity for inactivated than resting channels

Question 4

How to achieve selectivity for LAs?

Answer 4

Deliver LA to limited area (most LAs are topical and not in pill form)

Question 5

What are some factors the affect LA action?

Answer 5

1. Lipid solubility - more lipid soluble more potent and act longer
2. Size - smaller nerves>bigger nerves
3. Frequency of firing - high (sensory)>low (motor)
4. Position - circumferential>deep (large nerve trunk)
5. Myelination - myelinated>nonmyelinated
6. pH dependency - alkaline (low proportion of ionised molecules)>acidic

Question 5

Example of ester-type

Answer 5

Procaine, cocaine, tetracaine, benzocaine

Question 5

Example of amide-type

Answer 5

Lidocaine, mepivacaine, bupivacaine

Question 5

What is the method of metabolism for ester-type LA?

Answer 5

Plasma/tissue non-specific esterases

Question 6

What is the method of metabolism for amide-type LA?

Answer 6

Hepatic enzymes

Question 7

What happens in phase I of systemic distribution?

Answer 7

Steep exponential decline in [LA] and rapid distribution in blood and highly perfused organs

Question 8

What happens in phase II of systemic distribution?

Answer 8

Slower decline in [LA] and distribution to less well perfused tissue

Question 9

What can unintended large dose of LA lead to?

Answer 9

Systemic toxicity

Question 10

What can LA combine with to prevent LA systemic distribution from site of action?

Answer 10

Epinephrine

Question 11

Which LA is more cardiotoxic?

Answer 11

Bupivacaine

Question 12

Toxic effects of cocaine

Answer 12

Blocks NA reuptake -> increased NA causes vasoconstriction and hypertension

Question 13

Toxic effects of O-toluidine (metabolite of prilocaine)

Answer 13

Methaemoglobin (iv methyleneblue/ascorbic acid methaemoglobin to haemoglobin)

Question 14

What does hydrolysis of ester LAs lead to?

Answer 14

Ester LAs hydrolysed to PABA -> allergic reaction in small percentage of population

Question 15

2 ways of injected LAs

Answer 15

1. Epidural anaesthetics (Lidocaine, bupivacaine)
   -Regional nerve block
2. Dental anaesthesia (Lidocaine - short time, bupivacaine - long time)

Question 16

5 ways of topical LAs

Answer 16

1. Skin
   -minor burns/inflamed/wounds
2. Eye
   -remove foreign objects
3. Dental
   -applied to gum due to entry of injection needle
4. Otorhinolaryngology
   -insertion of endoscope for gastric ulcer scope
5. Gynaecology (Lidocaine)
   -episiotomy cuts

Question 17

What affects choice of drug?

Answer 17

-Duration of action
-Surface requires rapid penetration of skin and limited tendency to diffuse away

Question 18

What is the clinical use of cocaine?

Answer 18

Good penetration and vasoconstriction -> most often used for ENT procedures

Question 19

Difference between ester-type and amide-type LAs

Answer 19

1. Ester type occasionally cause allergic reaction but amide-type rarely cause allergic reaction
2. Ester-type is inactivated by blood esterases but amide-type is inactivated by liver enzymes