Local anaesthetics

Question 1

How do Local Anaesthetics Work on the Eye?

Answer 1

Local anesthetics (LAs) are used to provide temporary loss of sensation in the eye by blocking nerve conduction. They block voltage gated Na+ channels.

Question 2

Describe normal nerve conduction

Answer 2

1. Resting potential. No nerve impulse so a potential difference of –70mV is kept across the axon via sodium potassium pump. 3Na+ move out of cell, 2 K+ into cell.
2. During an action potential: Sodium channels open, allowing Na⁺ to flow into the cell. K+ channels remain closed.
3. This depolarizes the nerve membrane, membrane potetial goes from –70mV to +40mV triggering the nerve signal to travel along the axon.
4. Repolarisation. Na+ channels close, K+ channels open. K+ diffuse out of cell down concentration gradient.
5. Hyperpolarisation. K+ channels remain open longer than needed so membrane becomes hyperpolarised to –90mV. Sodium potassium pump brings it back to –70mV.
6. Refractory period. The period of time following an action potential in which the neuron can’t fire another action potential.

Question 3

Describe how Local Anaesthetics effect nerve conduction?

Answer 3

1. Local anesthetics, in their unionised (lipophilic) form, will cross the lipid membrane.
2. Once inside, the pH is slightly more acidic, so will become ionised.
3. The ionised form binds to the voltage gated sodium channels, blocking them.
4. This binding prevents sodium ions from entering the cell, preventing depolarisation and nerve signal transmission.
5. As a result, temporary loss of sensation.

Question 4

What are the factors which affect LA binding effects?

Answer 4

1. pKa levels - Lower pKa = more unionised = faster onset
   Higher pKa= longer duration of block
2. pH levels - Inflamed or infected tissue have a lower pH, more acidic, more ionised so less effective.
3. Metabolism of LAs - This depends on their aliphatic link.
4. Nerve morphology - the diameter of fibre determines sensitivity to being blocked. The smaller the diameter the more sensitive.
5. Amount of myelination of axon affects sensitivity to being blocked. Less myelination > Non myelination > Large myelination
6. Concentration of LA.

Question 5

Describe characteristics of ester link

Answer 5

1. Rapidly hydrolysed by pseudo-cholinesterases
2. Shorter half life
3. Hydrolysed to ParaAminoBenzoic Acid (PABA) causing allergic responses

Question 6

Describe characteristics of Amide link

Answer 6

1. Metabolised in liver by CYP450 enzymes
2. Longer half life
3. Rarely causes allergic reactions

Question 7

What is the need of formulation of LAs?

Answer 7

Local anaesthetics are weak bases so are largely unionised, thus poorly water soluble.

Local aneasthetics are formulated as HCl salts at a pH of 4-7 to increase solubility and stability. This makes it mostly ionised, but still works due to equilibrium; physiological buffers raise the pH so that unionised fraction increases.

Question 8

What are the ideal characteristics of LAs?

Answer 8

1. Quick onset of action –
   Depends on: Nerve fibre diameter, concentration, pH, pKa
2. Good duration and rate of removal – Depends on hydrolysis/metabolism (aliphatic link)
3. No effect on pupil size/ accommodation/ IOP -
   They do have an effect.
   Pachymetry – Transient corneal thickening can occur, can take measurement after 80 secs
   Tonometry – IOP reduction after 15mins, can take measurement between 1-15mins
4. No interference with Mydriatics, Cycloplegics, antibiotics.
5. No discomfort -
   Proxymetacain least stinging, Oxybuprocaine, Lidocaine, Tetracaine most stinging.
6. No local toxicity -
   They could cause allergic reactions
   They increase absorption of other drugs due to vasodilatory effects Indirect corneal damage from foreign body and rubbing eyes
   Direct damage from frequent use which melts cornea
   More stinging with dry eye patients
7. No interference with healing process -
   However, LA slows down healing
8. No systemic toxicity
   CNS and cardiovascular effects due to blocking Na+ channels.
   However, this is less of a problem due to ophthalmic LAs being in small doses, being applied topically, eye is less vascular, blood aqueous barrier.

Question 9

Name the Local anaesthetics

Answer 9

1. Proxymetacaine HCl
2. Oxybuprocaine HCl
3. Tetracaine HCl
4. Lidocaine HCl

Question 10

What are the legal classifications for each of the LAs?

Answer 10

All are POMs. Optometrists can use in clinics but can’t prescribe.

Never used for the management of ocular symptoms
Never prescribed for use at home.

Question 11

Which LA to use if you need to take a corneal / conjunctival swab?

Answer 11

Proxymetacaine as it doesn’t have antibacterial properties unlike the others.

Question 12

Explain why less myelination is the most sensitive to LAs?

Answer 12

Lower myelination means that the nerve still has exposed nodes of Ranvier, where local anesthetics can effectively block Na+ channels and stop conduction.

Unmyelinated require more time or a higher concentration of the drug because the anaesthetic has to diffuse across the entire fiber

Largely myelinated means the myelination prevents the anaesthetic from easily reaching the nodes of Ranvier and blocking the Na+ channels.

Question 13

Name the applications of each

Question 14

Name the advantages of each

Question 15

Name the disadvantages of each