pharm: local anaesthesia

Question 1

What are the classes of LA?

Answer 1

Ester-type & Amide-type

Question 2

How are ester-type LAs metabolised & excreted?

Answer 2

By plasma / tissue non-specific esterases in blood (hence inactivated in blood)
→ metabolites travel to kidney for excretion

Question 3

How are amide-type LAs metabolised and excreted?

Answer 3

Metabolised by hepatic enzymes (usually CYP450) (hence inactivated in liver)
** contraindicated in pts with liver disease!

Question 4

Do LAs cause allergic reactions?

Answer 4

Ester-type occasionally causes allergic reactions.
Amide-type rarely cause allergic reactions.

Question 5

List ester-type LAs.

Answer 5

Don’t have letter “i” before prefix (before “-caine”)

Cocaine
Procaine
Tetracaine
Benzocaine

Question 6

List amide-type LAs

Answer 6

Has letter “i” in prefix (before “-caine”)

Lidocaine
Mepivacaine
Bupivacaine
Etidocaine
Prilocaine
Ropivacaine

Question 7

What is the mechanism of action of LAs?

Answer 7

LAs stop nerve conduction by blocking sodium channels in the axon membrane → prevent sodium entry → slow down or bring conduction to a halt.

Question 8

Explain the use-dependency of LAs.

Answer 8

Passage of train of action potentials causes sodium channels to cycle through open and inactivated states.
Depth of LA nerve block increases with action potential frequency because:
1. LAs gain access to the channel more readily when the channel is open.
2. LAs have higher affinity for the inactivated channels than for the resting (closed) channels.

Question 9

How to achieve selectivity for LAs?

Answer 9

Deliver LAs to a limited area.
(because LAs are non-selective & block action potentials in all accessible neurones)

Question 10

List factors affecting LA action.

Answer 10

1. Lipid solubility
2. Characteristics of nerves
3. Physiological pH

Question 11

How does lipid solubility affect LA action?

Answer 11

More lipid soluble drugs: more potent and act longer

More lipid soluble (& hence hydrophobic): bupivacaine, tetracaine
Less lipid soluble (& hence hydrophobic): lidocaine, procaine, mepivacaine

Question 12

Describe the characteristics of nerves that are blocked first.

Answer 12

Size: Smaller (#1)
Frequency of firing: High
Position: Circumferential
Myelination: Myelinated (#2)

Question 13

Assuming equal frequency of firing and position, rank the characteristic axons in order of which is blocked first to last.

Answer 13

Small myelinated axons > small non-myelinated axons > large myelinated axons
Nociceptive & Sympathetic transmission is blocked first.

Question 14

Explain how pH affects LA action.

Answer 14

LAs are weak bases, mainly ionised at physiological pH.
Alkaline pH: small proportion of LA ionised → increased LA activity
Acidic pH: large proportion of LA ionised → decreased LA activity

Question 15

Short acting LAs?

Answer 15

Procaine (Novocaine) – Ester-type LA

Question 16

Medium acting LAs?

Answer 16

Lidocaine (Lignocaine, Xylocaine) – Amide-type LA
Mepivacaine (Carbocaine, Isocaine) – Amide-type LA

Question 17

Long acting LAs?

Answer 17

Tetracaine (Pontocaine) – Ester-type LA
Bupivacaine (Marcaine) – Amide-type LA

Question 18

How to prevent LA systemic distribution and systemic toxicity?

Answer 18

Combine LA with Epinephrine to prevent LA systemic distribution from site of action

Question 19

In what instances do LAs cause toxic effects?

Answer 19

Unintended large dose of LA via IV / intra-arterial → systemic circulation → systemic toxicity
Excessive topical application → absorption into bloodstream → systemic circulation → systemic toxicity

Question 20

What are the toxic effects of Bupivacaine & its contraindications?

Answer 20

More cardiotoxic than most other LAs.
Contraindicated in CVS-compromised pts.

Question 21

What are the toxic effects of Cocaine?

Answer 21

Cocaine blocks norepinephrine uptake → increases vasoconstriction → causes hypertension

Question 22

What are the toxic effects of O-tuluidine (metabolite of prilocaine)? Can it be treated?

Answer 22

Causes methaemoglobin (When Fe2+ in haem group of Hb is oxidised to Fe3+)
Treated with: IV Methyleneblue or Ascorbic acid → converts methaemoglobin to haemoglobin

Question 23

Describe how adverse side effects may occur for ester-type LAs.

Answer 23

Ester LAs are hydrolysed to p-aminobenzoic acid (PABA) derivatives → cause allergic reactions in a small percentage of population

Question 24

List some topical applications of LAs.

Answer 24

Skin: minor burns, inflammed wounds
Eye: remove foreign objects
Dental: applied to gum before entry of injection needle
Otorhinolaryngology: insertion of endoscope for gastric ulcer scope
Gynaecology: episiotomy cuts (lidocaine)

Question 25

List some injected applications of LAs.

Answer 25

Lidocaine, Bupivacaine: Epidural anaesthetics, Dental anaesthesia