Local anaesthetics

Question 1

Outline the physiology of an action potential

Answer 1

Question 2

What are the potential mechanisms of action of local anaesthetics?

Answer 2

• Sodium (or K/Ca) channel blockers
• Block nerve impulse propagation
• Complete sensation blockage (anaesthesia)

Question 3

Outline the structure of a local anaesthetic agent.

Answer 3

1. An aromatic ring - lipophilic
2. Amine - hydrophilic
3. Intermediate amide/ ester

Question 4

Name three amino-ester and three amino-amide local anaesthetics.

Answer 4

1. -ester
   
   1. Cocaine
   2. Procaine
   3. Benzocaine
2. -amides
   
   1. Lidocaine
   2. Mepivacaine
   3. Bupivacaine
   4. Ropivacaine

Question 5

How are local anaesthetics metabolised in the body?

Answer 5

1. -ester - hydrolysed by plasma pseudocholinesterases
2. -amides - liver metabolism

Question 6

Explain the concept of weak bases and how it relates to action of local anaesthetics.

Answer 6

Weak bases are partially dissociated (inequilibrium depending on pH)

pKa is the pH at which the agent is half ionised

• Non-ionised drug (B) can cross membrane
• Ionised drug (BH+) cannot but bind Na+ channel internally

Question 7

How does speed of onset of LAs relate to the pKa of a substance?

Order these LAs as to their speed of onset.

Procaine, bupivacaine, ropivacaine, lidocaine and mepivacaine.

Answer 7

Inversely related to pKa. So….

1. A more alkaline (higher pKa) = more ionised, slower onset
2. A more acidic (lower pKa) = less ionised, faster onset

P (5 mins), L/C (10 mins), B/ R (30 mins)

Question 8

How does the duration of action of LAs relate to protein binding and vasoactivity?

Order these LAs according to their duration of effect.

Bup, Rop, Lido, Mepiva, Pro

Answer 8

1. Protein binding = longer lasting (more ionized at 7.4)
2. Vasoactivity = Faster systemic absorption during vasodilation = shorter effect

P (1H), L (1.5H), M (2H), R/B (4H)

Question 9

How does potency of LAs relate to lipid solubility and molecular size?

Which LAs are most potent?

Answer 9

1. Lipid solubility = > is more potent
2. Smaller = more soluble

More able to cross membrane barriers

Rop/bup

Question 10

Which type of afferent nerve fibres are most susceptible to nerve blocks?

Order Aa, Ab, Ad, c and b

Answer 10

1. Aa motor - most susceptible
2. Ab touch/proprioception
3. Ad/C temperature/pain
4. B sympathetic - least susceptible

Question 11

Name a LA which is highly selective for C and A fibres.

Answer 11

Ropivacaine and bupivacaine (more than others)

Question 12

Outline the factors which affect LA activity in the body.

Answer 12

1. Concentration - greater degree and duration
2. Volume - higher extension
3. Acidity - decreased activity at acidic pH due to greater ionisation
4. Vascular absorption - vasoconstriction leads to increased duration

Question 13

Systemic absorption of LAs results in…

Answer 13

1. Liver/ kidney metabolism/ excretion
2. Side effects when reach heart and brain

Question 14

What side effects can result from systemic absorption of LAs?

Answer 14

Increased at higher doses.

• Neurotoxicity
  
  • Sedation
  • Visual disturbances
  • Seizures
  • Coma
• Cardiotoxicity
  
  • Arrhythmias
  • Cardiac arrest

Question 15

Order these LAs in terms of their cardiotoxic effects.

• Ropivacaine
• Lidocaine
• Bupivacaine
• Procaine
• Mipivacaine

Answer 15

Least - P/L/M

High - R

Most - B

Question 16

Why should LAs be deposited around rather than directly into a nerve?

Answer 16

Can cause direct nerve damage.

Mepivacaine is the least toxic

Question 17

What systemic effects can lidocaine have which are used beneficially?

Answer 17

• Anti-arrhythmic
• Systemic analgesia
• Decreased anaesthetic requirement
• Pro-kinetic GI
• Anti-endotoxic
• Anti-inflammatory
• Neuro-protectant (< intra-cranial pressure)

Question 18

Which LA is the only product liscenced in FPAs?

Answer 18

Procaine