Local anaesthtics - AI from notes

Question 1

What form do local anaesthetics (LA) take when injected?

Answer 1

Injected as a solution

They are stored as ionized hydrochloride salt at a low pH.

Question 2

At what pH are local anaesthetics stored for stability?

Answer 2

pH of 5-6

Question 3

What happens to local anaesthetics once injected into the body?

Answer 3

They become unionized at pH 7.4

Question 4

What are the two forms that local anaesthetic dissociates into at physiological pH?

Answer 4

• Unionized form
• Ionized form

Question 5

Which form of local anaesthetic is lipid soluble and can cross the cell membrane?

Answer 5

Unionized form

Question 6

What is the pH inside the cell where local anaesthetics bind to sodium channels?

Answer 6

pH 7.1

Question 7

How do local anaesthetics affect sodium channels?

Answer 7

They prevent the sodium channel from leaving the inactive state

Question 8

What are the two main structural types of local anaesthetics?

Answer 8

• Esters
• Amides

Question 9

What enzyme breaks down esters?

Answer 9

Pseudo-plasma esterase enzymes

Question 10

What is a characteristic of esters regarding their stability?

Answer 10

They are more unstable in light and have a short shelf life.

Question 11

How are amides metabolised?

Answer 11

In the liver

Question 12

What is the effect of the R antomer of local anaesthetics?

Answer 12

More cardio-toxic and more selective for cardiac voltage-gated ion channels.

Question 13

What factors influence the absorption of local anaesthetics?

Answer 13

• Method of administration (injection, spray, transcutaneous)
• pKa and percentage of unionized component

Question 14

How does pKa affect the onset of action of local anaesthetics?

Answer 14

Higher pKa leads to greater ionized form and slower onset; lower pKa leads to faster onset.

Question 15

Why are local anaesthetics generally ineffective in infected tissue?

Answer 15

Due to the low pH of infected tissue.

Question 16

What is the relationship between protein binding and duration of action for local anaesthetics?

Answer 16

Greater protein binding correlates with greater duration of action.

Question 17

Which type of local anaesthetic is more extensively protein bound?

Answer 17

Amides

Question 18

What is the effect of conditions like MI, pregnancy, and renal failure on protein binding?

Answer 18

Protein binding is increased.

Question 19

Do amides cross the placenta?

Answer 19

Yes

Question 20

Do esters cross the placenta?

Answer 20

No

Question 21

What determines in vivo potency of local anaesthetics?

Answer 21

Lipid solubility

Question 22

What determines in vitro potency of local anaesthetics?

Answer 22

• Vasodilator properties
• Duration of action

Question 23

How are esters metabolised?

Answer 23

Ester linkage is broken by plasma esterase’s rapidly in the blood.

Question 24

What are the cardiac effects of local anaesthetics?

Answer 24

• Block cardiac Na channels
• Can treat arrhythmias but also cause them
• Myocardial depressant properties

Question 25

What is a specific cardiac toxicity property of bupivacaine?

Answer 25

Has greater affinity for Na channels and slower dissociation, leading to greater cardiac toxicity.

Question 26

What is the CNS effect of local anaesthetics?

Answer 26

* Rapid penetration of the brain * Bi-phasic effect (inhibitory and excitatory phenomena)

Question 27

What is Intralipid used for?

Answer 27

Treatment of local anaesthetic toxicity.

Question 28

What is the initial bolus dose for Intralipid treatment?

Answer 28

20% intralipid 1.5mg/kg over 1 min.

Question 29

What is the infusion rate for Intralipid after the initial bolus?

Answer 29

0.25ml/kg/min.