Local anaesthetics

Question 1

What is the difference between inactivation and deactivation of voltage-gated ion channels?

Answer 1

Inactivation: ion flow blocked by gating mechanism
Deactivation: ion flow blocked by closing of channel

Question 2

MoA of local anesthetics:

Answer 2

• Stop axonal conduction by blocking sodium channels in axonal membrane when applied locally in appropriate concentration – prevent sodium ion entry
• Drug protonated in low pH, unable to be passed through the bilayer to enter the nerves to exert its action
• Drug is active when protonated
• non-selective modifiers of neuronal function, block action potentials in all neurons to which they have access

Question 3

Factors affecting LA action:

Answer 3

• More lipid soluble drugs are more potent and act longer
  (e. g. tetracaine, etidocaine, bupivacaine)
• Acts on all nerves (small > big, circumferential > deep, myelinated > non-myelinated)
• pH dependency: increased activity in alkaline pH and decreased in acidic pH

Question 4

Main differences between ester type and amide type local analgesics:

Answer 4

Ester type: low incidence of allergy, metabolised by plasma/tissue non-specific esterases
Amide type: very low incidence of allergy, metabolised by hepatic enzymes

Question 5

Notable ester-type local analgesics:

Answer 5

cocaine, procaine, tetracaine, benzocaine

Question 6

Notable amide-type local analgesics:

Answer 6

lidocaine, mepivacine, bupivacaine, etidocaine, prilocaine, ropivacaine

Question 7

Cautions in use of LA:

Answer 7

• Unintended large dose of LA if accidentally injected IV/intra-arterially can cause systemic toxicity
• Excessive LA injected locally can result in high blood level following absorption –> onset of toxic symptoms and signs may appear late compared to direct IV scenario

Question 8

Toxic effects of LA (in general) :

Answer 8

• CNS: sleepiness –> visual auditory disturbances –> restlessness –> nystamus –> shivering –> convulsion –> stoppage of vital functions –> death
• CVS: Cardiac contraction –> arteriolar dilatation –> hypotension –> CV collapse

Question 9

Which LA has the most cardiotoxic effects?

Answer 9

Bupivacaine –> may combine with epinephrine and can reduce bleeding

Question 10

Toxic effects of cocaine:

Answer 10

CNS & CVS effects,

Vasoconstriction and hypertension: due to NA reuptake blocked

Question 11

Toxic effects of prilocaine. How to reverse one of the toxic effect?

Answer 11

CNS & CVS effects

methaemoglobin: caused by O-toluidine (prilocaine metabolite) – reversed by IV methylene blue/ascorbic acid

Question 12

Toxic effects of ester LAs:

Answer 12

Allergic reaction due to PABA derivatives –> skin rash/anaphylactic shock

Question 13

How to chose LA used:

Answer 13

• duration of action
• surface anaesthesia requires rapid penetration of skin and limited tendency to diffuse away (fast onset)
• cocaine gives good penetration and vasoconstriction but any amount can lead to abuse

Question 14

Clinical applications of topical LA:

Answer 14

Skin: minor burns/wounds/inflammation
Eye: removal of foreign objects
Dental: applied to gum due to entry of injection needle
Otorhinolaryngology: insertion of endoscope for gastric ulcer
Gynecology: episiotomy cuts (lidocaine)

Question 15

Common surface anaesthesia:

Answer 15

lidocaine, tetracaine, dibucaine, benzocaine – not effective for skin

Question 16

uses of infiltration anaesthesia:

Answer 16

Direct injection into tissues to reach nerve branches and terminals
for minor surgery

Question 17

Caution during use of infiltration anaesthetics:

Answer 17

epinephrine or felypressin usually added as vasoconstrictors (not with fingers or toes)
only suitable for use in small areas or will have high risk of systemic toxicity

Question 18

Reason for use of nerve-block anaesthesia:

Answer 18

less LA needed than for infiltration anasthesia

Question 19

Caution during use of nerve-block anesthetics:

Answer 19

• Accurate placement of needle is important
• onset of anesthesia may be slow
• duration of anesthesia may be increased by addition of vasoconstrictor

Question 20

LA used in epidural anesthesia:

Answer 20

lidocaine, bupivacaine

Question 21

How does epidural anaesthesia work, and what is it used for?

Answer 21

LA injected into epidural space, blocking spinal roots

used for surgery to abdomen, pelvis or leg, when GA cannot be used and for painless childbirth

Question 22

side effects of epidural anaesthesia:

Answer 22

postoperative urinary retention

other SEs similar to spinal anaesthetics:

• bradycardia, hypotension
• respiratory depression

Question 23

How spinal anaesthesia work:

Answer 23

• LA injected into subarachnoid space (containing CSF) to act on spinal roots and spinal cord
• used for surgery to abdomen, pelvis or leg, when GA cannot be used

Question 24

How to limit spread of LA during spinal anaesthesia:

Answer 24

glucose can be added, tilt patient

Question 25

Side effects of spinal anaesthesia:

Answer 25

main risks: bradycardia, hypotension owing to systemic block, respiratory depression due to effects on phrenic nerve or respiratory center, avoided by minimising cranial spread
- postoperative urinary retention (block of pelvic autonomic outflow) is common

Question 26

How is intravenous regional anaesthesia administered:

Answer 26

LA injected IV distal to a pressure cuff to arrest blood flow, and remains effective until circulation is restored

Question 27

Use of intravenous regional anaesthesia:

Answer 27

limb surgery

Question 28

Caution for use during intravenous regional anaesthesia

Answer 28

risk of systemic toxicity when cuff is released prematurely – risk smaller when cuff remains inflated for at least 20 mins

Question 29

drugs used as intravenous regional anaesthesia:

Answer 29

Lidocaine, prilocaine

Question 30

Drugs used as spinal anaesthesia:

Answer 30

mainly lidocaine

Question 31

LA dose may be reduced with:

Answer 31

combination with opioid (fentanyl) if epidural anaesthetics (lidocaine, bupivacaine)

Question 32

Injected LA for dental use:

Answer 32

lidocaine is short duration, bupivacaine for longer duration