Local Anaesthetics (DONE)

Question 1

What is local anaesthesia?

Answer 1

The loss of sensation in a limited region of the body

LAs are important drugs to anaesthetists as we use them for regional anaesthesia

Question 2

Spinal anaesthesia

Answer 2

Can only put needle in from L2 downwards so tends to be used for operations on hips, knees etc.

Question 3

Epidural anaesthesia

Answer 3

Needle can be put anywhere in epidural space up to and including cervical, can leave catheter in, can continue analgesia for as long as you need cf. spinal 90-120 minutes

Question 4

Regional nerve block

Answer 4

Can anaesthetise upper limb through brachial plexus in neck e.g. in patients who don’t want general anaesthetic

Question 5

Structure of a local anaesthetic

Answer 5

Lipophilic aromatic ring
Intermediate (ester or amide chain)
Terminal amine

Question 6

Local anaesthetics preparations

Answer 6

Formulated as the hydrochloride salt making them water soluble
Can contain adrenaline- can increase dose to give prolonged action, but increases risk of toxicity
Can contain glucose giving a heavy formulation for use in spinal anaesthesia- sinks below CSF when patient lying down for use in lower limb surgery

Question 7

Physicochemical characteristics

Answer 7

Potency correlated to lipid solubility
Duration of action closely associated with amount of protein binding
Onset of action closely related to pKa
Local anaesthetics are weak bases

Question 8

High and low pKa

Answer 8

High pKa: greater fraction is ionised, unable to penetrate lipid membrane, slow onset of action
Low pKa: increased fraction unionised, able to cross lipid membrane, faster onset of action

Question 9

Mechanism of action

Answer 9

Local anaesthetics interrupt neural conduction by inhibiting the influx of sodium ions
Physically block the trans-membrane pore
Two main blocking pathways: hydrophobic via the membrane, hydrophilic via the mouth of the channel

Question 10

pH of LAs

Answer 10

Syringe: pH 6.9, local anaesthetic is water soluble
Extracellular: pH 7.4, balance shifts towards unionised
Intracellular: pH 7.1, balance shifts towards ionised

Question 11

Blocking fibres

Answer 11

Local anaesthetics block conduction in small diameter nerve fibres more readily than in large fibres
Pain sensation is blocked more readily than other sensory modalities (touch etc.); motor axons are also relatively resistant

Question 12

Toxicity

Answer 12

1:10,000 for epidurals and 1:1000 for peripheral nerve blocks, depending on the type of block
Important to know toxic doses:
Lidocaine- 3mg/kg (6mg with adrenaline)
Bupivacaine- 2mg/kg

Question 13

Intralipid

Answer 13

The event of local anaesthetic induced cardiac arrest that is unresponsive to standard therapy, in addition to standard cardio-pulmonary resuscitation

Question 14

Surface/topical anaesthesia

Answer 14

Lipid-soluble drugs e.g. lidocaine are used that are absorbed from mucous membranes
Risk of systemic toxicity only when concentrations and large areas are involved- sensitisation/irritation can occur

Question 15

Examples of surface/topical anaesthesia

Answer 15

Lidocaine- patches (neuralgia), ear, nose, oropharyngeal use, EMLA, teething gel
Amethocaine- eye drops, haemorrhoidal preparations
Dibucaine- haemorrhoid ointment
Tetracaine- ophthalmic preparations
Benzocaine- used as a dry powder to dress painful skin ulcers, as throat lozenges/spray, used in condoms to delay ejaculation

Question 16

Lidocaine

Answer 16

Amide, class 1b antiarrhythmic
Fast onset, moderate duration
pKa: 7.9 (mainly ionised)
% unionisd at pH 7.4: 25%
Protein binding 70%

Question 17

Bupivacaine

Answer 17

Amide, racemic mixture S- and R- enantiomer (levobupivacaine is the pure S-enantiomer)
Moderate onset, long duration
pKa: 8.1
% unionised at pH 7.4: 15
Protein binding: 95%

Question 18

Cocaine

Answer 18

Ester
Topical anaesthesia and vasoconstriction
Stimulates CNS
Hyperthermia, arrhythmias, hypertension
pKa 8.6
5% unionised at pH 7.4
95% protein binding

Question 19

EMLA

Answer 19

Eutectic mixture of local anaesthetics
Mixture of the crystalline bases of 2.5% lidocaine and 2.5% prilocaine
Lower melting point so an oil at room temp
Avoid in congenital/idiopathic methaemoglobinaemia