Local Anaesthetic Agents

Question 1

Are local anaesthetic agents weak acids or weak bases?

Answer 1

Weak bases

Question 2

What is the pKa of lidocaine and roughly what proportion is ionised at biological pH?

Answer 2

7.9 and 75% is ionised

Only the unionized molecules are able to pass through the axonal membranes. Lidocaine, with a lower pKa than bupivacaine, therefore has a faster onset due to this higher proportion being unionized.

Question 3

What is the pKa of bupivacaine and roughly what proportion is ionised at biological pH?

Answer 3

8.1 and 85% is ionised.

Only the unionized molecules are able to pass through the axonal membranes. Lidocaine, with a lower pKa than bupivacaine, therefore has a faster onset due to this higher proportion being unionized.

Question 4

What proportion of lidocaine is protein bound? How does this compare to bupivacaine? And what is the clinical result of these differences?

Answer 4

Lidocaine is 70% bound with a maximum duration of action of 90-120 minutes

Bupivacaine is 95% bound with a duration of action of several hours

Question 5

Determine whether the following are true or false regarding safe doses of LA:

A local infiltration of 20 ml 0.25% Chirocaine® (levobupivacaine) in a 60 kg male following inguinal hernia repair provides a safe dose of 50 mg

Answer 5

True.

Chirocaine 0.25% = 2.5 mg/ml
Total dose given = 20 x 2.5 mg = 50 mg
Maximum safe dose for 60 kg patient = 60 x 2.5 mg = 150 mg

Question 6

Determine whether the following are true or false regarding safe doses of LA:

A spinal anaesthesia of 3 ml 0.5% heavy Marcaine® (bupivacaine) for a 75 kg female for a hysteroscopy and D&C provides a safe dose of 15 mg

Answer 6

True.

Marcaine 0.5% = 5 mg/ml.
Total dose given = 3 x 5 mg = 15 mg
Maximum safe dose for patient = 75 x 2 = 150 mg

Question 7

Determine whether the following are true or false regarding safe doses of LA:

A transverse abdominis plane (TAP) block in an 82 kg male for a laparotomy using 60 mls 0.375% Chirocaine® provides a safe dose of 225 mg

Answer 7

False.

Chirocaine 0.375% = 3.75 mg/ml.
Total dose given = 3.75 x 60 = 225 mg
Maximum safe dose = 2.5 x 82 = 205 mg

Question 8

Determine whether the following are true or false regarding safe doses of LA:

An epidural top-up in a 56 kg female for lower segment Caesarean section (LSCS) of 25 mls 0.5% chirocaine® 15 minutes after a rescue dose of 10 ml 0.25% chirocaine provides a safe dose of 140 mg

Answer 8

False.

Chirocaine 0.5% = 5 mg/ml, 0.25% = 2.5 mg/ml.
Top up for LSCS = 25 x 5 = 125 mg
Earlier top up = 2.5 x 10 = 25 mg
Total dose given = 150 mg
Maximum safe dose for 56 kg patient = 56 x 2.5 = 140 mg

Question 9

What is the maximum safe dose of lidocaine (with and without adrenaline)?

Answer 9

3 mg/kg without adrenaline

7 mg/kg with adrenaline

Question 10

What is the maximum safe dose of bupivacaine (with and without adrenaline)?

Answer 10

2 mg/kg without adrenaline

2.5 mg/g with adrenaline

Question 11

What is the maximum safe dose of levobupivacaine (with and without adrenaline)?

Answer 11

2.5 mg/kg - not used with adrenaline

Question 12

What is the maximum safe dose of ropivacaine (with and without adrenaline)?

Answer 12

3-4 mg/kg - not used with adrenaline

Question 13

What is the maximum safe dose of prilocaine (with and without adrenaline)?

Answer 13

6 mg/kg without adrenaline

9 mg/kg with adrenaline

Question 14

Regarding the structure and groups of local anaesthetics used in practice (true or false):

Local anaesthetics are made of two distinct parts, a lipophilic aromatic ring and a hydrophilic tertiary amine group

Answer 14

False. Local anaesthetics have three distinct parts, a lipophilic aromatic ring, a hydrophilic tertiary amine group and a link that defines it as either an ester or an amide.

Question 15

Regarding the structure and groups of local anaesthetics used in practice (true or false):

The structure of the aromatic ring and hydrocarbon chain dictates the lipid-solubility of the drug

Answer 15

True. The structure of the aromatic ring and hydrocarbon chain dictates the lipid-solubility of the drug, which in turn influences potency.

Question 16

Regarding the structure and groups of local anaesthetics used in practice (true or false):

Ester local anaesthetics can be stored for longer than amide local anaesthetics

Answer 16

False. The ester link is less stable and, therefore, cannot be stored for the same length of time as amide local anaesthetics.

Question 17

Regarding the structure and groups of local anaesthetics used in practice (true or false):

All local anaesthetics exist in a greater proportion at an unionized state at physiological pH

Answer 17

False. At physiological pH, local anaesthetics exist in a greater proportion at an ionized state.

Question 18

Regarding the structure and groups of local anaesthetics used in practice (true or false):

The structure of link between the lipophilic aromatic ring and the hydrophilic tertiary amine group determines the class of local anaesthetic

Answer 18

True

Question 19

Regarding the mechanism of action of local anaesthetics used in practice (true or false):

Local anaesthetic agents block the propagation of action potentials along neuronal axons

Answer 19

True. Local anaesthetic agents are membrane stabilizers that block the propagation of action potentials along neuronal axons.

Question 20

Regarding the mechanism of action of local anaesthetics used in practice (true or false):

Local anaesthetics bind to the sodium channel and block the influx of sodium ions to inhibit nerve conduction

Answer 20

True. Local anaesthetic agents block the sodium-potassium channels of the phospholipid membrane in order to stop propagation of the action potential. Their degree of action is thought to be due to the number of ‘open’ sodium channels that the anaesthetic is able to bind to and thereby render inactive.

Question 21

Regarding the mechanism of action of local anaesthetics used in practice (true or false):

The more lipid-soluble a drug, the more is required to penetrate the neuronal membrane and exert an effect

Answer 21

False. The more lipid-soluble a drug, the less is required to penetrate the neuronal membrane and exert an effect. It is, therefore, more potent and smaller amounts are used.

Question 22

Regarding the mechanism of action of local anaesthetics used in practice (true or false):

Changes in physiological pH have a marked effect on the speed of onset of the local anaesthetic

Answer 22

True. Only the unionized molecules are able to pass through the axonal membranes. Lidocaine, with a lower pKa than bupivacaine, therefore has a faster onset due to this higher proportion being unionized. The effect of pH is important and any changes in physiological pH has a marked effect on the activity of these drugs and their speed of onset

Question 23

Regarding the mechanism of action of local anaesthetics used in practice (true or false):

Unmyelinated fibres are blocked prior to myelinated fibres

Answer 23

False. Myelinated fibres are blocked prior to unmyelinated fibres.

Question 24

Regarding the pharmacology of local anaesthetics (true or false):

The vasodilation effect of some local anaesthetics leads to an increased rate of absorption

Answer 24

True

Question 25

Regarding the pharmacology of local anaesthetics (true or false): The metabolism of a local anaesthetic is class-dependent

Answer 25

True. The metabolism of a local anaesthetic is dependent on its group, and this influences its half-life and, in turn, its duration of action.

Question 26

Regarding the pharmacology of local anaesthetics (true or false): Prilocaine is metabolized in the blood by plasma esterases

Answer 26

False. Prilocaine and other amide local anaesthetics such as lidocaine and bupivacaine are metabolized in the liver. Ester local anaesthetics such as procaine, cocaine and tetracaine undergo hydrolysis at their ester linkage site by plasma esterases.

Question 27

Regarding the pharmacology of local anaesthetics (true or false): Adrenaline can be used to prolong the effect of some local anaesthetics

Answer 27

True. Adrenaline is often co-administered with local anaesthetics to counteract the vasodilator actions, and to potentiate the effects in the area needed. The slower the absorption from the site of administration, the longer the desired effects.

Question 28

Regarding the pharmacology of local anaesthetics (true or false): Caution should be used regarding doses of local anaesthetics applied to highly vascular areas to minimize systemic absorption

Answer 28

True. Local anaesthetics tend to be administered directly to the area in which the effect is needed. The amount absorbed systemically depends on the vascularity of the area to which the drug has been applied. The epidural space is more vascular than subcutaneous administration and, therefore, enables greater absorption.

Question 29

Regarding local anaesthetic toxicity and its treatment (true or false): Local anaesthetics may cause allergy, an increase of methaemoglobin in the blood, acidosis in cases of fetal stress and cardiotoxic side-effects

Answer 29

True

Question 30

Regarding local anaesthetic toxicity and its treatment (true or false): When using local anaesthetics, a high degree of suspicion of local anaesthetic toxicity is needed when unusual or unexpected neurological or cardiovascular symptoms present

Answer 30

True. There are several factors that increase the risk of local anaesthetic toxicity. Blocks involving large volumes such as epidural or Bier's blocks increase this risk. The vascularity of the site also increases or decreases the risk.

Question 31

Regarding local anaesthetic toxicity and its treatment (true or false): Early neurological symptoms of local anaesthetic toxicity include altered taste, perioral tingling and tinnitus

Answer 31

True. The early neurological excitatory symptoms of local anaesthetic toxicity include altered taste, perioral tingling and tinnitus. Symptoms of the progression of the toxicity includes motor twitching, grand mal seizures and coma.

Question 32

Regarding local anaesthetic toxicity and its treatment (true or false): Cardiovascular symptoms of local anaesthetic toxicity present as cardiac arrhythmias that respond well to early treatment

Answer 32

False. Cardiac arrhythmias can occur and these may be prolonged and refractory to traditional treatment. Ultimately, complete cardiovascular collapse and cardiac arrest can result.

Question 33

Regarding local anaesthetic toxicity and its treatment (true or false): Treatment of local anaesthetic toxicity involves the use of Intralipid®, which prevents the local anaesthetic agent from being absorbed

Answer 33

True. The treatment of local anaesthetic toxicity involves seizure management, airway protection, life support strategies and a regimen of Intralipid® as part of adjuvant treatment specific to the local anaesthetic plasma levels.

Question 34

In the treatment of a female paediatric patient weighing 8 kg who presents with local anaesthetic toxicity, the Intralipid® regimen is: A. Initial bolus: 8 ml Initial infusion rate: 120 ml/hour Increased infusion rate: 200 ml/hour B. An initial bolus: 12 ml Initial infusion rate: 120 ml/hour Increased infusion rate: 200 ml/hour C. Initial bolus: 12 ml Initial infusion rate: 120 ml/hour Increased infusion rate: 240 ml/hour D. Initial bolus: 8 ml Initial infusion rate: 120 ml/hour Increased infusion rate: 250 ml/hour E. Initial bolus: 12 ml Initial infusion rate: 12 ml/hour Increased infusion rate: 240 ml/hour

Answer 34

C. The initial bolus is 8 kg x 1.5 ml/kg = 12 ml. The initial infusion is 8 kg x 15 ml/kg/hour = 120 ml/hour. The increased infusion rate is 8 kg x 30 ml/kg/hour = 240 ml/hour. Maximum cumulative dose is 12 ml/kg.

Question 35

Regarding bupivacaine, are the following statements true or false? Bupivacaine is enantiopure

Answer 35

False. In the commercial presentation of this local anaesthetic there is a 50:50 proportion: levobupivacaine, L (-) isomer, and dextrobupivacaine D (+) isomer. This preparation which contains both enantiomers is called a racemic mixture. In an enantiomerically pure drug (or enantiopure), all of its molecules have (within limits of detection) the same chirality sense. Note that the term homochiral as a synonym is strongly discouraged. Thus levobupivacaine rather than bupivacaine (which is a racemic mixture) is enantiomerically pure.

Question 36

Regarding bupivacaine, are the following statements true or false? Toxicity is rare in nephrotic syndrome

Answer 36

False. Protein binding of levobupivacaine is more than 97%, mainly to acid alpha1-glycoprotein, rather than to albumin. This union to proteins is somewhat higher than the union of racemic bupivacaine to proteins (95%). This means that less than 3% is free in plasma. It is the free levobupivacaine, a small fraction of the total concentration that can have an action on other tissues, causing side effects, and toxicity. In hypo-proteinaemic, undernourished patients, patients with the nephrotic syndrome and in the newborn there is less protein for binding, causing higher levels of free drug, resulting in toxic effects being seen at lower doses.

Question 37

Regarding bupivacaine, are the following statements true or false? The L isomer of bupivacaine has a higher potential for neurotoxicity

Answer 37

False. Interest in levobupivacaine arose after several cases of severe cardiotoxicity (including death) were reported where it was shown that the D isomer of bupivacaine had a higher potential for toxicity. Consequently, it was thought that if it was possible to use only the levorotatory isomer, levobupivacaine, the risk for cardiac and neurotoxicity could be less than with the racemic bupivacaine but with similar clinical effects.

Question 38

Regarding bupivacaine, are the following statements true or false? Blockade of the sodium channels is stereoselective

Answer 38

True. Electrophysiological studies have been made which demonstrate that blockade of the sodium channels is stereoselective, with the D isomer being more potent and faster than the L isomer.

Question 39

Regarding bupivacaine, are the following statements true or false? The pKa of levobupivacaine is similar to the pKa of racemic bupivacaine

Answer 39

True. The pKa of levobupivacaine is 8.1, similar to the pKa of the racemic bupivacaine.

Question 40

Regarding local anaesthetics (true or false): Ropivicaine is more potent than lidocaine

Answer 40

True. Ropivacaine is four times more potent than lidocaine, reflecting its greater lipid solubility.