Local Anaesthetics

Question 1

What is a local anaesthetic drug?

Answer 1

• Reversibly prevents transmission of the nerve impulse - In region to which is applied - Without affecting consciousness

Question 2

What are there two types of local anaesthetics?

Answer 2

Esters (only have one ‘i’ in the name) Amides (all contain 2 or more ‘i’s’ in the name - for the exception of 2…)

Question 3

What are local anaesthetics composed of?? How do the two different types of local anaesthetics differ in composition?

Answer 3

Composed of two groups:

• Lipid soluble hydrophobic aromatic group
• Charged, hydrophilic amide group

Esters - groups joined by ESTER link

Amides - groups joined by AMIDE link

Question 4

What is the difference between Esters and Amides?

Answer 4

Stability

• Esters are comparitively less stable in solution ∴ shorter shelf life
• Amides = more stable (~2 yr shelf life). Also, are heat stable and can be autoclaved

Allergic Reactions

• Esters metabolised to para-aminobenzoate (PABA) = ass with allergic reactions
• Amides rarely causes allergic reactions

Question 5

What factors determine the physiochemical and clonical characteristics of local anesthetics?

Answer 5

• pKa of Local anaesthetic
  
  • pH at which both ionised (charged) and unionised (uncharged) forms of LA exist in equal amounts.
  • Unionised drug pass through lipid membrane more readily vs ionised
  • ∴ drug which = more unionised at physiological pH (i.e. lower pKa) will reach its target site more quickly than the drug which is less so e.g. lignocaine pKa 7.9 vs bupivacaine pKa 8.1
• Drug solubility
  
  • Higher the lipid solubility, the higher the drug penetration into cell memebrane ∴ higher the potency (amount required to produce given effect)
• Degree of Protein Binding
  
  • ​The higher the protein binding (i.e. albumin), the longer the duration of effect

Question 6

Why are local anaesthetics ineffective in infected tissue?

Answer 6

• Acidic environment further ↓ unionised drug fraction available to diffuse into and block the nerve.
• Also ↑ vascularity = ↑ drug removal

Question 7

What are the two proposed mechanisms by which local anaesthetics work?

Answer 7

1. Unionised lipid-soluble drug passes through phospholipid membrane where it is then ionised ► binds to Na+ channel, holding them in an inactive state ► stops depolarisation ► prevents AP transmission. Has a membrane satbilising effect
2. ‘Membrane expansion’ Unionised drug dissolves into the phospholipid membrane ► cause Na+ channel/lipoprotein matrix to swell ► inactivation.

Question 8

What are short acting Ester local anaesthetics?

Answer 8

Procaine

Benzocaine

Cocaine

Question 9

What is the medium acting ester local anaesthetic?

Answer 9

Prilocaine

Question 10

What are the long acting ester local anaesthetics?

Answer 10

Amethocaine

Question 11

What are the medium acting amide local anaesthetics? What are their doses?

Answer 11

• Lidocaine (Lignocaine) without adrenaline 3mg/kg
• Lidocaine (Lignocaine) with adrenaline 7mg/kg
• Mepivacaine

Question 12

What are the long acting amide local anaesthetics? What are their doses?

Answer 12

Bupivacaine/Levobupivacaine (with or without adrenaline) 2mg/kg
Ropivacaine

Question 13

What is the short acting amide local anaesthetics? What is its dose?

Answer 13

Prilocaine without adrenaline - 6mg/kg

Ptrilocaine with adrenaline - 8 mg/kg

Not often used on wards but drug of choice for Biers block

Question 14

Why can you use higher doses when local anaesthetics are combined with adrenaline?

Answer 14

• Causes vasoconstriction ∴ reduces drug absorption and toxicity.
• Also prolongs block duration (except for long acting bupivacaine or ropivacaine) and reduces blood loss

Question 15

Which types of fibres are more affected by local anaesthetics? How does this translate to sensation?

Answer 15

• Small nerve fibres = ↑ sensitive
• Myelinated fibres are blocked before non-myelinated fibres of the same diameter.
• ∴ loss of nerve function proceeds as:
• Pain ► temperature ► touch ► proprioception ► skeletal muscle tone.

Question 16

What routes can local anaesthetics be administered by?

Answer 16

• *Topical** - EMLA (Eutactic mixure of LA’s), Ametop
• *Mucosal** - ENT procedures
• *Tissue infiltration** - around incision
• *Peripheral nerve block** – e.g. femoral
• *Plexus block** – e.g. brachial
• *Epidural**
• *Spinal**

Question 17

What are the local anaesthetic additives? What do they do?

Answer 17

• Adrenaline - vasoconstrictor. ↓ drug removal (prolongs action) ↓ absorption (toxicity) and ↓ blood loss
• Clonidine - alpha-2 adrenoreceptor agonist. Prolongs and intensifies blocks when added to local anaesthetics (↓ sympathetic drive)
• Sodium bicarbonate - ↑pH of environment thus ↑unionised form ► ↑ speed of onset
• Glucose - added to bupivacaine - ↑baricity of solution to greater than that of CSF. When administered as spinal, ↑ spread of solution in intrathecal space

Question 18

What are the side effects of local anaesthetics? Which LA is most dangerous? Which LA is safest?

Answer 18

• All LAs toxic if sufficient amounts absorbed into systemic circulation.
• Perioral/tongue paraesthesia, a metallic taste, and dizziness ► Slurred speech ► diplopia ► tinnitus ►confusion, restlessness ► muscle twitching ► convulsions ► coma ►respiratory arrest ► cardiac arrest
• Bupivacaine = most dangerous as v cardiotoxic (arrhythmias ↓ myocardial contractility)
• Lignocaine - can be used as an antiarrhythmic (low doses)

Question 20

What is the underlying mechanism for LA SEs?

Answer 20

• Initially excitatory Sx ► inhibition of inhibitory neurons via GABA receptors
• Later, neuronal depression ► widespread Na channel blockade

Question 21

What is the Tx for Local anaesthetic Toxicity?

Answer 21

Question 22

How do you work out doses for local anaesthetics?

Answer 22

• 1% Lignocaine means 1g/100ml
• i.e. 1000 mg/100ml
• i.e. 10mg/ml

e.g. Safe dose of lignocaine with adrenaline = 3 mg/kg.

For 70kg 210mg. For 1% lignocaine…

= 1000 mg per 100ml or 10mg/ml

► 210/10 = 21 ml