Local anaesthetic pharmacology

Question 1

Key pharmacology for how pain treated in animals.

Answer 1

Drug enters nerve and blocks Na+ channels.
Preferential nociceptive blockade before proprioceptive mechanoreceptive and motor blockade.
Ionisation is important (weak bases).
2 forms – esters and amides – affects breakdown.
Side effects on CNS and CVS.

Question 2

Difference between LA and GA?

Answer 2

LA = meds that cause absence of all sensation (incl. pain) in a specific body part w/o loss of consciousness.
GA = eliminate all sensation in the entire body and cause unconsciousness.

Question 3

When / how are LAs used?

Answer 3

• Part of a balanced anaesthetic regimen (e.g. regional infiltration or epidural in a patient under GA).
• Provide anaesthesia in standing, conscious patient (e.g. local block for equine / farm animal surgery).
• Postoperative for procedures (e.g. topical LA into thorax via chest drain).
• Desensitisation for procedures (e.g. topical on cat larynx for ET intubation or EMLA on rabbit ear vein prior to IV catheterisation).
• Lameness investigation in horses (sequence of nerve blocks to pin down painful joint).

Question 4

What is the difference between epidural and spinal anaesthesia?

Answer 4

For epidural, anaesthetics injected into the epidural space (via catheter).
But for spinal, anaesthetic injected directly into the cerebrospinal fluid (via a much smaller needle).

Question 5

Procaine…
1. Licensed for which spp?
2. All licensed versions contain what?
3. Duration of action?
4. Side effects?

Answer 5

1. Horses, dogs and cats (not often used in dogs and cats).
2. Adrenaline.
3. 50 mins (short acting).
4. Can get allergic reactions due to PABA.

Question 6

Lidocaine…
1. Licensed for which spp?
2. Onset of action?
3. Duration of action?
4. Side effects.

Answer 6

1. Horses. dogs, cats, and used in rabbits.
2. 2-5 mins.
3. 20-40 mins (short acting).
4. Lower cardiotoxicity than bupivacaine.

Question 7

Bupivacaine…
1. Licensing?
2. Onset of action as compared to lidocaine?
3. Duration of action?
4. Side effects / risks?

Answer 7

1. Not licensed but widely used in dogs, cats and rabbits.
2. Longer.
3. 6 hours (long acting).
4. Cardiotoxicity.

Question 8

Mepivacaine…
1. Licensed for use in which spp?
2. Use?
3. Duration of action?
4. Risks?

Answer 8

1. Horses.
2. In horses for digital nerve blocks.
3. 2 hours (short duration).
4. Potency and toxicity slightly higher than lidocaine.

Question 9

Ropivacaine…
1. Licensing?
2. Duration of action?
3. Risks?

Answer 9

1. Not licensed but used in small animals.
2. Up to 6 hours (long acting).
3. Lower CVS and CNS toxicity than bupivacaine.

Question 10

EMLA…
1. What is it?
2. Licensing?
3. Use?
4. Onset of action?
5. Use for rabbits?

Answer 10

1. Mixture of lidocaine and prilocaine in a cream.
2. Not licensed but used in SA.
3. Topical anaesthesia.
4. 30-45 mins.
5. Ear IV catheterisation.

Question 11

Proparacaine and tetracaine…
1. Licensing?
2. Use?
3. Duration of action?
4. container?

Answer 11

1. Not licensed.
2. Ophthalmological preparations available for desensitisation of the cornea.
3. 15 mins in cats and 45 mins in dogs.
4. Single use pipettes.

Question 12

1. What does potency mean?
2. Relationship between LA toxicity and potency?

Answer 12

1. The measure of drug activity expressed in terms of the amount required to produce an effect of given intensity.
2. As LA potency increases, so does toxicity.

Question 13

What are the factors that affect the duration of action of LAs?

Answer 13

• Ease of penetration and amount of drug reaching the sodium channel: lipid solubility.
• Strength of binding to the channel: property of some drugs.
• Speed of removal: depends on tissue perfusion (addition of vasoconstrictors ee.g. adrenaline).
• Metabolism of LA: ester vs amide.

Question 14

How will you know if the LA contains esters or amides?

Answer 14

Amides have an ‘i’ before the ‘caine’ in their name e.g. lidocaine, but esters do not e.g. procaine.

Question 15

How are esters metabolised?

Answer 15

Hydrolysis of the ester link by plasma esterases such as cholinesterases.
PABA formed as a product of hydrolysis (can provoke allergic reactions).
Note: CSF does not contain esterases.

Question 16

How are amide metabolised?

Answer 16

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

Question 17

1. What forms does lidocaine come in?
2. How is the poor water solubility of LAs generally overcome? – how does this work? – Drawback of this?

Answer 17

1. • Sterile solutions for parenteral use.
     - Aerosol sprays for nasal / airway use.
     - Topical patches.
2. Making a salt solution. – Lowers pH of the solution if a hydrochloride. – can cause stinging on injection.

Question 18

1. What is baricity?
2. What is the comparator substance for spinal anaesthesia?
3. Why is it important to consider baricity?
4. How LA solutions for epidural or spinal use made heavier?

Answer 18

1. The weight of one substance compared with the weight of an equal volume of another substance.
2. CSF.
3. We don’t want our LA to spread too high into epidural space or could affect muscles of respiration etc.
4. Glucose added to them.

Question 19

1. What is a commonly added vasoconstrictor for LAs and why is it added?
2. Consideration of care?

Answer 19

1. Adrenaline to reduce the speed of systemic absorption and therefore prolong the duration of action.
   Reduces the risk of toxicity.
   Reduces bleeding at the injection site.
2. Care with end arterial sites as can get ischaemia.

Question 20

1. How can LAs be toxic?
2. What must a drug be to be systemically active?
3. How does plasma protein binding affect action and toxicity?
4. How does pH relate to toxicity?

Answer 20

1. When absorbed systemically, they are available for systemic effects i.e. toxicity.
2. Unbound and unionised.
3. LAs which bind more easily to plasma proteins have a longer duration of action and lower risk of toxicity.
4. Lower pH reduces affinity for protein binding and increases risk of toxicity.

Question 21

1.What are the 2 key areas of toxicity of local anaesthetic?
2. What is the biggest overall risk factor of toxicity?
3. What are other considerations associated with risks of local anaesthesia toxicity?

Answer 21

1. Neurotoxicity and cardiovascular toxicity.
2. Dosage.
3. • Site of injection which determines the rate of uptake into the systemic circulation.
     - Care with smaller patients – essential to give accurate dose so use correctly sized syringes.

Question 22

What symptoms are seen with CNS toxicity?

Answer 22

Generalised CNS depression that is proportional to the unbound drug.
Minor behavioural changes.
Muscle twitching and tremors.
Tonic-clonic convulsion.
CNS depression / respiratory depression and death.

Question 23

How is CNS toxicity treated?

Answer 23

Symptomatically.
Benzodiazepines to control seizures.
Oxygen supplementation.
Intubation and controlled ventilation if needed.

Question 24

What is seen with cardiovascular toxicity?

Answer 24

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

Dysrhythmias
– Most commonly seen with bupivacaine.
– Lipophilicity means rapid entry to open sodium channels during systole.
– Drug remains bound to the sodium channel during diastole.

Question 25

How is the cardiovascular toxicity treated?

Answer 25

Symptomatically.
Manage bradycardias with an anticholinergic e.g. atropine.
Fluid therapy w/ inotropic support if needed.
Intralipid IV may be successful to mop up LA.

Question 26

How do we prevent toxicity of LA?

Answer 26

Do not exceed the safe maximum dose.
If greater volume needed, dilute LA w/ NaCl 0.9%.
Use appropriately sized syringed to draw up dose for accuracy.
Use appropriately sized needles to minimise tissue trauma.
Aspirate before injection to confirm not in a blood vessel.