2. Pain Management: Local Anaesthetics

What are local anaesthetics and their use?

• Local anaesthetics cause a loss of sensation to pain in a specific area without affecting consciousness.

• They are used for minor surgical procedures.

• Cocaine was the first local anaesthetic.

All local anaesthetics are ____ bases.

All local anaesthetics are weak bases.

What is the structure of local anaesthetics & what are the 2 classes?

• Local anaesthetics have a general structure with:

  • Aromatic ring (lipophilic)

  • Intermediate linkage (either ester or amide)

  • Terminal amine (hydrophilic)

• They are all weak bases.

• Amino esters and amino amides are the two classes of local anaesthetics.

How can you identify if a medicine is a local anaesthetic?

Most local anaesthetics end with -caine (e.g., lidocaine, bupivacaine, procaine).

What are the characteristics of amino esters as local anaesthetics?

• Unstable in solution and fast-acting

• Rapidly metabolised in plasma by pseudocholinesterases

• Excreted in urine

• Metabolic product PABA (para-aminobenzoic acid) causes allergic reactions

• Examples:

  • Cocaine

  • Procaine

  • Benzocaine

  • Tetracaine (used in venous cannulation)

  • Chloroprocaine (used in spinal anaesthesia)

What are amino amides and how do they differ from amino esters?

• Amino amides are heat stable, have a long shelf life, and are less likely to cause allergies.

• They are metabolised in the liver and have a slower onset and longer half-life than amino esters.

• Examples with uses:

  • Lidocaine (dentistry)

  • Bupivacaine (epidural block)

  • Levobupivacaine (acute post-operative pain)

  • Mepivacaine (nerve block anaesthesia)

  • Prilocaine (minor skin procedures)

  • Ropivacaine (peripheral nerve block)

  • Articaine (dentistry)

how is local anaesthetic injected.

near a nerve, but not directly in the blood.

How do local anaesthetics work?

• Local anaesthetics are weak bases, injected as salts (ionised form).

• They shift to the non-ionised form, allowing them to pass through the neuronal membrane.

• Inside the cell, they return to the ionised form, blocking voltage-gated sodium channels.

• This prevents depolarisation, stopping action potential and pain transmission.

What are the states of voltage-gated sodium channels, and how do they relate to local anaesthetics?

• Three states:

  • Deactivated (closed): At resting membrane potential.

  • Activated (open): At threshold (~-55mV), leading to depolarisation.

  • Inactivated (closed): After depolarisation, leading to the falling phase.

• Local anaesthetics bind to sodium channels, blocking them in the inactivated state, preventing action potentials and pain transmission.

• They are applied near nerves to prevent pain for as long as needed.

How do local anaesthetics affect different nerve fibres and what is their order of sensitivity?

• Local anaesthetics block nerve fibres in the order of their diameter:

  • Aδ (1–5 μm): Sharp pain (myelinated)

  • Type C (0.2–1.5 μm): Dull pain & autonomic postganglionic (unmyelinated)

  • Aβ (5 μm): Sensory (myelinated)

  • Aα (12 μm): Motor (myelinated)

• In myelinated fibres, local anaesthetics act at the Nodes of Ranvier.

• The order of nerve sensitivity is:

  • Autonomic > Pain > Temperature > Touch > Pressure (Proprioception) > Skeletal Muscle Tone.

What factors influence the activity of local anaesthetics?

• Lipid solubility = higher lipid solubility = higher potency

• Volume of agent

• Sites of injection

• pKa value = lower pKa = lower degree of ionisation = better cell penetration = faster onset rate = longer duration of action

How does pH influence anaesthetic activity?

• Most local anaesthetics have a pKa of ~7.6 – 8.9

• At pH 7.4, the ionised cationic form predominates

• At alkaline pH = low proportion of ionised molecules = increased onset of action & effect duration

• In inflamed tissues (acidic pH) = decreased onset & effect duration

How do vasoconstrictors affect local anaesthetics?

• Most local anaesthetics cause vasodilation (except cocaine)

• Adding vasoconstrictors prolongs local effects

• Not suitable for patients with severe hypertension or unstable cardiac rhythm

• Example: Lidocaine + Adrenaline

What are the symptoms of local anaesthetic toxicity?

• Central Effects:

  • CNS irritability → Seizures

  • Tinnitus, lightheadedness, metallic taste in mouth

  • Nausea, slurred speech, drowsiness

  • CNS depression

  • Agitation, confusion, dizziness, blurred vision

  • Muscle twitching, tremor

• Cardiovascular Effects:

  • Depression of cardiac conduction and excitability → Slowing/blocking of heart's electrical signals.

  • Atrio-ventricular block

  • Cardiovascular collapse

  • Cocaine → Enhances sympathetic activity, leading to tachycardia, increased cardiac output, vasoconstriction, and increased arterial pressure.

What is the treatment for local anaesthetic toxicity?

• Stop injection

• Seizure treatment with benzodiazepines

• Cardiovascular support: adrenaline, vasopressors, cardioversion

• Lipid emulsion therapy

What is lipid rescue & how is it used in local anaesthetic toxicity?

• 20% lipid emulsion (Intralipid) used to scavenge uncharged local anaesthetic molecules

• Aqueous IV infusion of fine lipid droplets

• Used in severe toxicity

• NICE guideline:

  • 1.5 mL/kg over 1 min

  • Followed by 15 mL/kg/hour

  • Can be repeated twice during cardiac arrest

What are the clinical applications of topical & regional nerve block anaesthesia?

• Topical anaesthesia:

  • Applied to mucous membranes (nose, mouth, trachea, genitourinary tract), cornea, or skin

  • E.g. lidocaine, tetracaine, benzocaine (not used in ophthalmology/ for eye)

• Regional nerve block:

  • Injected near a peripheral nerve trunk or plexus (e.g. dental nerves)

  • Used for regional anaesthesia in dentistry/surgery

  • May include vasoconstrictor

What are the clinical applications of infiltration & spinal anaesthesia?

• Infiltration anaesthesia:

  • Direct injection near nerve branches & terminals

  • Used for minor surgery

  • Adrenaline often added for vasoconstriction

• Spinal anaesthesia:

  • Injected into lumbar subarachnoid space (below L2) into CSF

  • Blocks spinal roots or cord

  • Used in abdominal & lower body surgery

What is epidural anaesthesia used for & how is it administered?

• Drug injected into the epidural space at any spinal level

• Blocks spinal roots

• Produces anaesthesia of the thorax, abdomen & lower limbs

What are some properties & side effects of the cocaine (e.g. cocaine, procaine, benzocaine)?

• Cocaine:

  • First local anaesthetic

  • Effective surface anaesthetic

  • Used in otolaryngology (e.g. nasal spray – low dose)

  • Side effects:

    • Euphoria

    • ↑ Sympathetic activity = tachycardia, ↑ cardiac output & arterial pressure, vasoconstriction

    • Addictive – never given by injection

• Procaine (Novocaine®): first cocaine derivative

• Benzocaine: low potency & toxicity, used topically (e.g. throat lozenges)

What are the properties, uses & side effects of lidocaine?

• Properties:

  • Hypoallergenic (less likely to cause allergic reactions)

  • Rapid onset

  • Effective for several hours

• Administration methods:

  • Injections (e.g. dental cartridges)

  • Surface anaesthesia: gel, ointment, solution, cream (EMLA®), jet spray

  • Topical solution for ear, nose, oropharynx (with phenylephrine)

• Side effects:

  • Confusion

  • Respiratory depression

  • Convulsions

  • Hypotension

  • Bradycardia

What are the properties, uses & side effects of bupivacaine?

• Properties:

  • Longer duration of action than other local anaesthetics

  • Slow onset (~30 min)

• Uses:

  • Principal drug for spinal anaesthesia

  • Suitable for continuous epidural analgesia in labour

• Side effects:

  • Similar to lidocaine (e.g. confusion, respiratory depression, convulsions, hypotension, bradycardia)