Local Anaesthetics

Question 1

What is the mechanism of LAs?

Answer 1

Block Na+ channel to block nerve conduction (action potentials)
“Membrane-stabilising effect”

Question 2

Describe preferential/differential block.

Answer 2

Larger diameter axons are more heavily myelinated so less susceptible to LA block
Will get nociceptive block before proprioceptive, mechanoreceptive and motor blockade

Question 3

Describe the structure of LAs.

Answer 3

Aromatic group (lipophilic end)
Basic side chain/tertiary amine (hydrophilic end)
EITHER ester OR amide linkage

Question 4

How does pKa affect onset of action of LAs?

Answer 4

Plasma pH = 7.4
pKa further from 7.4 = greater proportion of LA ionised
Greater ionisation = slower onset of action

Question 5

How does pH affect action of LAs?

Answer 5

Plasma pH = 7.4
pH decreases in inflamed tissue
Greater proportion of drug is ionised so less drug can penetrate nerve membrane to bind to Na+ channel
So LAs less effective in inflamed tissue

Question 6

Define potency.

Answer 6

A measure of drug activity expressed in terms of the amount required to produce an effect of given intensity

Question 7

What is the relationship between toxicity and potency of LAs?

Answer 7

LA toxicity increases as potency increases

Question 8

What factors affect duration of action of LAs?

Answer 8

Ease of penetration and amount of drug reaching Na+ channel (lipid solubility)
Strength of binding to channel
Speed of removal - dependent on tissue perfusion (addition of vasoconstrictors)
Metabolism of LA (ester vs amide)

Question 9

Describe ester linkages.

Answer 9

No ‘i’ in name before ‘caine’
Relatively unstable
Rapidly broken down by plasma psuedocholinesterase
Leads to a short plasma half-life

Question 10

Describe amide linkages.

Answer 10

‘i’ in name before ‘caine’
More stable than ester linkages
Subject to biotransformation with conjugation in liver
Longer plasma half-life

Question 11

How are ester linkages metabolised?

Answer 11

Hydrolysis of ester link by plasma esterases (e.g. cholinesterases)
PABA is formed as a product of hydrolysis (can provoke allergic reactions)

Question 12

How are amide linkages metabolised?

Answer 12

Broken down by cytochrome P450 enzymes
Hepatic disease can prolong or limit metabolism
Drugs such as barbiturates (that induce enzymes) can increase drug breakdown
Drugs that inhibit P450 enzymes (e.g. midazolam) can inhibit breakdown

Question 13

How are LAs formulated?

Answer 13

Generally poorly water soluble
Overcome this by making salt solution
Lowers pH of solution if hydrochloride salt (can cause stinging on injection)

Question 14

Define baricity.

Answer 14

Weight of one substance compared with weight of equal volume of another substance
e.g. for spinal anaesthesia, comparator substance is CSF

Question 15

How do we balance baricity for spinal anaesthesia?

Answer 15

Glucose added to solutions to make them heavier
To ensure LAs do not spread too high into epidural space (to avoid affecting muscles of respiration)

Question 16

Describe the addition of vasoconstrictors to LAs.

Answer 16

Reduce risk of toxicity
Reduce bleeding at injection site
Care with end arterial sites as can get ischaemia
Adrenaline commonly added

Question 17

Why are vasoconstrictors added to LAs?

Answer 17

To reduce speed of systemic absorption
Prolong duration of action

Question 18

Describe plasma protein binding.

Answer 18

LAs are absorbed systemically so available for systemic effects e.g. toxicity
Drug must be unbound and unionised to be systemically active
Plasma protein binding is concentration- and pH-dependent
(% binding decreases as concentration rises or pH falls)

Question 19

Describe lidocaine.

Answer 19

Rapid onset of action (2-5 mins)
Intermediate duration of action (20-40 mins)
Lower cardiotoxicity than bupivacaine

Question 20

Describe bupivacaine.

Answer 20

Longer onset of action than lidocaine
Longer duration of action (up to 6 hours)
Greater CVS toxicity than lidocaine

Question 21

Describe EMLA.

Answer 21

Mixture of lidocaine and prilocaine in a cream
Topical anaesthesia - good for IV catheterisation
Onset of action 30-45 mins before full effect

Question 22

What are the risk factors for LA toxicity?

Answer 22

Dose!
Site of injection (determines rate of uptake into systemic circulation)
Smaller animals (essential to give correct dose so use appropriately-sized syringes)

Question 23

Describe CNS toxicity.

Answer 23

Seen at lower concentrations than CVS toxicity
Generalised CNS depression proportional to unbound drug

Question 24

What are the symptoms of CNS toxicity?

Answer 24

Minor behavioural changes
Muscle twitching/tremors
Tonic-clonic convulsions
CNS/respiratory depression
Death

Question 25

How do we treat CNS toxicity?

Answer 25

Symptomatic treatment
Benzodiazepines to control seizures
Oxygen supplementation
Intubation and controlled ventilation if required

Question 26

Describe hypotension as a symptom of CVS toxicity.

Answer 26

Depression of myocardial contractility
Direct relaxation of vascular smooth muscle
Loss of vasomotor sympathetic tone

Question 27

Describe dysrhythmias as a symptom of CVS toxicity.

Answer 27

Most commonly seen with bupivacaine
Lipophilicity means rapid entry to Na+ channels during systole
Drug remains bound during diastole
Presents as re-entrant arrhythmias

Question 28

How do we treat CVS toxicity?

Answer 28

Symptomatic treatment
Manage bradycardias with an anticholinergic
Fluid therapy with inotropic support if needed
Intralipid IV may be successful (mop up the LA)

Question 29

How can we prevent LA toxicity?

Answer 29

Do not exceed max. “safe” dose
If greater volume needed, dilute with 0.9% NaCl
Use appropriately-sized syringes for accuracy
Use appropriately-sized needles to minimise tissue trauma
Aspirate before injection to confirm not in blood vessel

Question 30

What are the possible loco-regional LA techniques?

Answer 30

Epidural
Regional/local
Topical
Infiltration

Question 31

What is the difference between spinal and epidural anaesthesia?

Answer 31

Spinal anaesthesia = injection into sac containing spinal cord, nerves and CSF
Epidural anaesthesia = injection into space around sac containing spinal cord, nerves and CSF

Question 32

Can RVNs carry out an epidural?

Answer 32

No! - into a body cavity

Question 33

What are the possible side effects of epidural anaesthesia?

Answer 33

Hypotension
Hypothermia
Urinarry retention
Infections
(Slowed hair regrowth)

Question 34

What is the difference between local and regional anaesthesia?

Answer 34

Arguably the same thing - may differ in size of affected area
Local e.g. infiltration = small discrete action
Regional = blocking a larger area

Question 35

Give some examples of local and regional anaesthesia.

Answer 35

Ophthalmic block
Dental block
Limb nerve block
IV regional anaesthesia
Intra-articular
Wound soaker catheters

Question 36

Give some examples of topical anaesthesia.

Answer 36

LA eye drops
Lidocaine spray for ET intubation of cats
EMLA cream for IV catheterisation

Question 37

Give some examples of infiltration anaesthesia.

Answer 37

Testicular
Ovarian ligament
Ring block
Incisional line block
Intraperitoneal

Question 38

How do you carry out infiltration anaesthesia?

Answer 38

Usually blind inject in a ‘V’ or inverse pyramid shape
Desensitises this ‘V’ of tissue