Ep.37b: Local Anaesthetic Quiz For The FRCA Primary

© GasGasGas – The FRCA Primary Anaesthetic Sciences Podcast 2025

Section 1: Mechanism of Action

Q1.1 How do local anaesthetic agents exert their effects on nerve conduction?

• Sodium channel blockade on internal aspect of voltage-gated sodium channels
• Must cross neuronal membrane in unionised form
• Re-ionises inside nerve to become active ionised form
• Use-dependent block – preferentially binds to open/activated channels
• Why pain fibres are preferentially blocked: C fibres (unmyelinated) are most sensitive, A-alpha fibres (heavily myelinated motor) are least sensitive

Q1.2 What type of drugs are local anaesthetics chemically?

• Amphipathic compounds with lipophilic aromatic ring and hydrophilic amine group
• Weak bases with pKa > 7.4
• Ionisation at physiological pH
• Joined by either amide or ester linkage

Section 2: Classification

Q2.1 How are local anaesthetic agents classified?

• Amide vs ester classification based on chemical linkage
• Memory aid: Amides have 2 i’s (bupivacaine, lidocaine), esters have 1 i (cocaine, procaine)

Q2.2 How are these agents metabolised? 

• Chemical structure differences
• Stability in solution
• Metabolism pathways (liver N-dealkylation for amides vs plasma and tissue esterases for esters)
• Esters more likely to cause allergic reactions/skin reactions
• Amides last longer due to liver-only metabolism

Q2.3 Why are ester local anaesthetics associated with more allergic reactions?

• Role of PABA breakdown products (para-amino-benzoic acids)
• Amide allergic reactions are very rare

Section 3: Pharmacokinetic Properties

Q3.1 What factors determine the onset of action of local anaesthetics?

• pKa values and degree of ionisation
• Lower pKa = more unionised fraction = faster onset
• Clinical example: lidocaine (pKa 7.7, 25% unionised) vs bupivacaine (pKa 8.1, 15% unionised)

Q3.2 What factors determine the duration of action?

• Protein binding percentage – higher binding = longer duration
• Vascularity and washout
• Addition of vasoconstrictors (adrenaline)
• Bupivacaine 95% protein bound vs lidocaine 64-70% protein bound

Q3.3 What is the significance of pKa in local anaesthetic action?

• Definition of pKa
• Henderson-Hasselbalch equation application
• Lower pKa = faster onset (more unionised fraction available)

Section 4: Specific Agent Comparisons

Q4.1 Compare and contrast lidocaine and bupivacaine

• Chemical classification (both amides)
• pKa values (7.7 vs 8.1)
• Protein binding (64-70% vs 95%)
• Onset times: lidocaine faster (20-30 seconds skin, 3-5 min nerve) vs bupivacaine slower (10-20 min)
• Duration: lidocaine 90min-3hrs vs bupivacaine 5-16 hours
• Maximum safe doses: lidocaine 3mg/kg (7mg/kg with adrenaline) vs bupivacaine 2mg/kg
• Toxicity: bupivacaine highly cardiotoxic vs lidocaine moderate cardiotoxicity

Q4.2 How does levobupivacaine differ from bupivacaine?

• Pure S-enantiomer vs racemic mixture of R and S enantiomers
• Reduced cardiotoxicity – the major selling point
• Less motor block at low concentrations
• Same maximum dose: 2mg/kg (some sources say 2.5mg/kg but exam-safe to use 2mg/kg)

Q4.3 What are the advantages of ropivacaine over bupivacaine?

• Differential blockade – less motor block relative to sensory block
• Sensory block onset similar to bupivacaine, motor block slower onset and faster recovery
• Lower cardiotoxicity – higher maximum dose: 3mg/kg
• Pure S-enantiomer preparation

Q4.4 Describe the properties of prilocaine

• pKa 7.7-7.9 and 33% unionised – good onset characteristics
• EMLA cream composition: 2.5% lidocaine + 2.5% prilocaine
• Methaemoglobinaemia risk at doses >600mg (>10mg/kg) due to O-toluidine metabolite
• Maximum dose: 6mg/kg (8mg/kg with felypressin)
• Used for Bier’s blocks and day surgery spinals

Section 5: Clinical Applications

Q5.1 Why might a local anaesthetic block fail in infected tissue?

• Lower tissue pH (more acidic) reduces unionised fraction
• Increased ionisation of drug
• Enhanced washout due to hyperaemia –
  • if you’ve ever had a filling and then gone for a run anecdotally your numbness gets cleared! And I wonder if this is why large doses of epidural local for top ups actually wears off quite quickly because of the high cardiac output of the parturient!
• Adding bicarbonate can help by raising pH

Q5.2 How can you improve the onset time of local anaesthetics?

• Addition of sodium bicarbonate to raise pH
• Increases unionised fraction
• Particularly useful with lidocaine
• Note: bicarbonate precipitates with bupivacaine, levobupivacaine and ropivacaine

Q5.3 What is EMLA cream and how does it work?

• Eutectic Mixture of Local Anaesthetics
• Composition: 2.5% lidocaine + 2.5% prilocaine
• Onset: 1-2 hours, Duration: up to 5 hours
• Topical anaesthesia for procedures

Section 6: Toxicity and Safety

Q6.1 What are the maximum safe doses of common local anaesthetics?

• Lidocaine: 3 mg/kg (7 mg/kg with adrenaline)
• Bupivacaine: 2 mg/kg
• Levobupivacaine: 2 mg/kg
• Ropivacaine: 3 mg/kg
• Prilocaine: 6 mg/kg (8 mg/kg with felypressin)
• Cocaine: 1.5 mg/kg topically

Q6.2 What factors affect local anaesthetic toxicity?

• Total dose administered
• Site of injection and absorption rates
• Patient factors: cardiac output, acidosis, beta-blockers
• Inadvertent intravascular injection

Q6.3 Rank injection sites by systemic absorption rate

• Intercostal > Caudal > Epidural > Brachial plexus > Subcutaneous
• Remember: “ICEBS”
• Clinical significance for toxicity risk

Q6.4 What are the systemic effects of local anaesthetic toxicity?

• CNS effects: biphasic response (initial excitation of inhibitory interneurons → then depression)
• Early signs: perioral tingling, tinnitus, metallic taste, agitation
• Late signs: seizures, coma, respiratory depression
• Cardiovascular effects: initial hypertension → hypotension, arrhythmias, cardiac arrest

Q6.5 What precautions should you take to avoid toxicity?

• Dose calculations using ideal body weight
• Drug selection (e.g., levobupivacaine vs bupivacaine for safety)
• Injection technique: aspiration before injection, incremental dosing
• Wait 4 hours between nerve blocks and IV lidocaine infusions

Q6.6 Describe the management of local anaesthetic toxicity

• ABC approach + ALS protocols
• Intralipid 20%: 1.5ml/kg bolus, then 15ml/kg/hr infusion
• Call for help immediately
• Treat seizures with benzodiazepines or propofol

Section 7: Special Considerations

Q7.1 Compare cocaine as a local anaesthetic

• Ester classification
• pKa: 8.6 (only 6% unionised at physiological pH)
• Dual mechanism: sodium channel blockade + central monoamine reuptake inhibition
• Causes vasoconstriction + sympathomimetic effects
• Still used in ENT surgery for excellent vasoconstriction
• Maximum dose: 1.5mg/kg topically
• Contraindicated in IHD, uncontrolled hypertension, porphyria

Q7.2 What is the mechanism behind differential nerve blockade?

• Fibre sensitivity order: C fibres (most sensitive) → B fibres → A-delta → A-gamma → A-beta → A-alpha (least sensitive)
• Unmyelinated fibres blocked first, heavily myelinated motor fibres blocked last
• Clinical relevance: sympathetic block → sensory block → motor block
• Test cold sensation (A-delta fibres) to assess block onset

Q7.3 How do you calculate safe dosing for local anaesthetics?

• Weight-based calculations using maximum mg/kg doses
• Consider injection site (higher absorption = lower doses)
• Example: 75kg patient, lidocaine 3mg/kg = max 225mg = max 22.5ml of 1% lidocaine
• With adrenaline: 7mg/kg = max 525mg = max 52.5ml of 1% lidocaine

Additional Clinical Pearls

Q7.4 Why should lidocaine be avoided for spinal anaesthesia?

• Transient neurological symptoms (TNS) incidence up to 33%
• 82-90% reduction in TNS when any other LA used instead of lidocaine
• TNS: buttock/leg pain and dysaesthesia lasting up to 7 days

Q7.5 What are the advantages of prilocaine for day surgery spinals?

• Faster recovery than bupivacaine
• Motor block recovery: 158 minutes vs 220 minutes for bupivacaine
• Dosing strategy: 10-20mg for saddle block, 40-60mg for procedures below T10

Q7.6 What is special about IV lidocaine infusions?

• Maximum rate: 120mg/hour regardless of weight
• Loading: 1.5mg/kg over 10 minutes, then 1.5mg/kg/hour
• Requires monitored bed space and lipid rescue available
• Evidence shows heterogeneous results with unclear distinct benefit
• Most complications from dosing errors

Key Clinical Pearls

• pKa closer to 7.4 = faster onset
• Intercostal blocks have highest systemic absorption
• Higher lipid solubility = greater potency
• Higher protein binding = longer duration
• Infected tissue = reduced efficacy

I hope you enjoyed this fun filled quizatz haderach, and your prescience for local anaesthetic pharmacology is refined to a crisp perfection!

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“Thanks for listening guys… Every day you are getting better at this. Take it day by day, don’t overcook yourself, don’t freak out, and keep studying!”

Podcast Information

Transcript – Gas Gas Gas – Local Anaesthetics Quiz Part 2

Pre-Quiz Introduction

00:49-01:16

I hope that you’ve maybe listened to the first part this morning and now or yesterday – now you’re listening to this second part and you’re going to smash through these questions and really reinforce that knowledge. If you’ve listened to that on your way to a night shift and now you’re coming home from a night shift in the car, I think you need to put some power metal on like DragonForce. Don’t listen to this, you’ll fall asleep in the car. But anyway, look out for yourselves. We’re going to get straight into it.

Mechanism of Action

01:17-01:57

How do local anaesthetic agents exert their clinical effects on conduction?

You’re right. They work on the internal aspect of the sodium channel, this being a voltage-gated sodium channel. But to do so they must cross the membrane of this nerve, and to do so they must be in their unionised form. They re-ionise inside that nerve, binding to these voltage-gated sodium channels, and they have a use-dependent block, i.e. they prefer to bind to channels that are open, not closed.

Fibre Selectivity

01:59-02:48

Why are some fibres more readily blocked than others?

This is based chiefly on how myelinated these fibres are. Unmyelinated fibres are exceedingly susceptible to local anaesthetic agent, whereas heavily myelinated fibres are more resistant. As an example, motor nerves – very rapid in their conduction, very myelinated – take the longest period of time for a clinical effect to be observed compared to sensory or autonomic nerves.

Chemical Classification

02:49-03:22

What type of drugs are local anaesthetics chemically?

Now this is a bit of an awkward question, but they are amphipathic compounds. Remember they have a lipophilic aromatic ring on one end and a hydrophilic amine group on the other end. They are linked with either an ester or an amide linkage.

Classification and Examples

03:24-04:17

How are local anaesthetic agents classified? Remember this is a classify or die question, folks. And then also please give me some examples of local anaesthetic agents in these classifications.

So remember it’s amide and ester, the two classes of local anaesthetic agents. Although ketamine also has some local anaesthetic effect, but let’s not go there.

And then naming some agents: amide agents – bupivacaine, levobupivacaine, ropivacaine, lidocaine, prilocaine; ester agents – cocaine, 2-chloroprocaine and then procaine if you’re looking for a third one.

Metabolism

04:18-05:06

How are these local anaesthetic agents metabolised?

And remember we’re back to our classification here guys, so you’d say amide anaesthetic agents are broken down in the liver by N-dealkylation, whereas ester agents are broken down by plasma and tissue esterases because they are ester-based agents. Esters break down more quickly than amide agents, but note that ester agents have a breakdown product called para-aminobenzoic acid (PABA), which has a proclivity for causing allergic reactions and irritation.

Onset Time Factors

05:07-05:46

What factors determine the onset time of a local anaesthetic agent?

So classically the lipophilicity of the agent dictated by the benzene rings – this is fairly consistent across a number of molecules. More importantly is the pKa of the molecule. pKa of a molecule being the pH at which the drug is 50-50% unionised. However, we’re more interested in the unionised fraction at physiological pH. Noting that the greater the unionised fraction, the faster the onset.

Duration Factors

05:47-06:27

What factors determine the duration of action of a local anaesthetic agent?

So the protein binding of the local anaesthetic has a significant impact. The higher the protein binding, the more prolonged the onset. But also it’s important to think about the vascularity of the space. Highly vascular space clears agent quicker. And whether or not you’ve introduced additives to that agent, such as adrenaline or clonidine that might cause local vasoconstriction or work synergistically with that agent to prolong the effect.

Lidocaine vs Bupivacaine Comparison

06:27-07:39

Compare and contrast lidocaine and bupivacaine.

Both of these agents are amide anaesthetics. The onset times differ. Lidocaine has a faster onset time than bupivacaine. Offset times – lidocaine offsets faster than bupivacaine, although this can be modified by the addition of adrenaline.

Pharmacokinetically, lidocaine has a greater unionised fraction at 25% because of its pKa of 7.7, whereas bupivacaine is 15% unionised, with a pKa of 8.1, and this dictates the onset times I’ve just mentioned.

The maximum safe dose of lidocaine is 3mg per kilo or 7mg per kilo with the addition of adrenaline, whereas bupivacaine safe dose is 2 milligrams per kilo. Bupivacaine is more cardiotoxic than lidocaine.

Levobupivacaine Properties

07:40-08:35

How does levobupivacaine differ from bupivacaine though, Doctor?

Bupivacaine is a racemic mixture of R and S enantiomers, whereas levobupivacaine is just the S enantiomer. The chief reason for doing this is that there is markedly reduced cardiotoxicity of levobupivacaine versus bupivacaine. You tend to see CNS toxicity effects of levobupivacaine before cardiovascular effects, giving you a greater opportunity and window to alter the clinical outcome of a toxicity event. Interestingly, at lower concentrations, it tends to produce more of a sensory than motor blockade.

Prilocaine Properties

08:35-09:31

Describe the properties of prilocaine, Doctor.

Prilocaine is another amide local anaesthetic agent. It has a pKa of 7.7 to 7.9 and is a third unionised, so it has excellent onset characteristics when used intrathecally. It is less protein bound than bupivacaine at 95% and lidocaine at 64-70%. Prilocaine’s protein binding is 55%. Therefore, its duration is shorter, but it may mean that there’s a greater free fraction of molecule at injection site. It’s also found within EMLA cream and historically had been used for Bier’s blocks. In high doses, it can cause a methaemoglobinaemia due to a metabolic byproduct of its hepatic clearance.

Local Anaesthetic Failure in Infection

09:31-10:17

Why might a local anaesthetic agent fail to achieve surgical field anaesthesia in an infected site?

This is chiefly an issue to do with the pharmacokinetic property of these agents, the pKa. Infected tissues are more acidic. This leads to a smaller unionised fraction of local anaesthetic agent available to cross nerve membranes and exert effect when injected into sites of a more acidic pH environment, i.e., infected. Equally, duration of action may actually be shortened if the site is hyperaemic courtesy of the inflammatory process.

Improving Onset Time

10:19-11:03

How might you go about improving the onset time of local anaesthetic agents?

This is primarily achieved with the addition of sodium bicarbonate to raise the pH of the solution. More importantly, it will raise the pH of the tissues the local anaesthetic agent is introduced into, increasing the unionised fraction leading to faster onset times as more agent crosses into neuronal cytoplasm. This is chiefly done with lidocaine. Bicarb is not optimally compatible with bupivacaine and levobupivacaine.

EMLA Cream

11:09-12:12

What is EMLA cream and what is it used for?

EMLA stands for Eutectic Mixture of Local Anaesthetics, being composed of 2.5% lidocaine, 2.5% prilocaine. Onset time, 1-2 hours, lasting for up to 5 hours if it remains on the skin long enough to exert its full effect. Its use is topical anaesthesia for procedures classically in paediatric practice for cannulation.

They might ask you to define what a eutectic mixture is, and a eutectic system or mixture is a homogeneous mixture that has a melting point lower than those of the constituents. In the case of local anaesthetics, these agents would be considered solid at room temperature, but become an oily preparation when mixed. In this case, you find them as an emulsion of oil and water.

Maximum Safe Doses

12:13-12:49

What are some maximum safe doses of common local anaesthetic agents?

Lidocaine 3mg per kilo, 7mg per kilo with adrenaline. Bupivacaine and levobupivacaine 2mg per kilo. Ropivacaine, 3mg per kilo. Prilocaine, 6mg per kilo. No one’s going to ask you about cocaine. And if they do, shame on them.

Systemic Toxicity Risk Factors

12:51-13:54

What factors influence local anaesthetic systemic toxicity?

And you probably could be quite clever and break this down into patient factors, environmental factors and anaesthetic factors. Patient factors would be their cardiac output, their hepatic function, their renal function, their body mass. Surgical factors – site of surgery, and therefore what you’re trying to block, if it’s a high absorption versus a low absorption tissue.

And then anaesthetic factors – I’d think about these in terms of human factors, so not doing a stop before you block. Patient being covered up prior to administering block, not having a mark on the patient, patients being poorly informed. Performing more than one block increases your risk of error. And not using ultrasound increases the odds of toxicity by four times.

Injection Sites by Absorption Rate

13:54-14:16

Please rank the injection sites in terms of most to least systemic absorption rate.

Whatever acronym you use here guys, remember that it starts with intercostal and then caudal and then epidural, then brachial plexus, and then subcutaneous.

Systemic Effects of Toxicity

14:18-15:21

What are the systemic effects of local anaesthetic systemic toxicity?

You should be able to say I break this down to central nervous system effects and cardiovascular system effects. Both seem to have an early and late stage.

CNS: sensory disturbance such as tinnitus, circumoral tingling, pressure in the ears, metallic taste in mouth, or other altered sensorium, leading to seizures, agitation, respiratory depression and coma.

Whereas cardiovascularly you may see a brief hypertension before finding a hypotensive state with poor inotropy and deranged cardiac conduction leading to an assortment of arrhythmias – VT, VF, asystole, bradycardia.

Toxicity Prevention Measures

15:27-15:52

What precautions can you apply to reduce the odds of toxicity when administering a regional nerve block?

Calculate the right dose. Choose an appropriate drug – levobupivacaine being safer than bupivacaine. Aspirate before you inject. Use incremental dosing. And remember that ultrasound reduces your chances of problems four times over.

Prilocaine vs Bupivacaine for Day Case Surgery

15:53-16:31

What are the advantages of prilocaine over bupivacaine for day case spinal anaesthesia?

Prilocaine’s prompt offset improves the chances of same-day discharge for patients having day case surgery. Noting that the motor block recovers after 158 minutes instead of 220 minutes. Just remember folks when you’re using prilocaine, it does fix pretty quick. So make sure you’re pretty rapid in lying that patient down, tipping them where you want them to be, or keeping them sat up if you’re aiming for that subtle block.

Closing

16:32-17:22

Okay, that is probably enough question fun times for you guys. I don’t want to stretch it out too long. You need to have an excellent weekend. There are going to be some more questions on the show notes for the episode if you’re really loving life. Or if you want to quiz your mates when you’re doing some practice. Anyway, thank you very much. Have a great weekend. And hope you’re enjoying the show. Cheerio and goodbye.

Thanks for listening, guys. I hope you found it useful. But if you found it awful, do let me know. Please like and subscribe, register with whichever podcast platform you find yourself using, and leave a comment if you think I need to square something away. I just want to make sure that you guys know that every day you are getting better at this. There is a bucket of content to try and consume, and it is like drinking from a fire hose. Take it day by day, don’t overcook yourself, don’t freak out, and keep studying.

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