LA and adrenaline

Question 1

Local anaesthetics contain which three main components?

Answer 1

• An aromatic ring, usually based on benzine
• An amide or ester link
• A terminal amine

Most modern local anaesthetics (except benzocaine) have an amide intermediate linkage.

Question 2

How do local anaesthetics work?

Answer 2

• Bind to sodium channels
• Inactivate sodium channels
• Prevent propagation of action potential

Local anaesthetic must diffuse across the cell membrane into the neuron to gain access to the sodium channel.

Question 3

Define a strong acid.

Answer 3

Completely dissociates in solution

Example: HCl.

Question 4

Define a weak acid.

Answer 4

Partially dissociates in solution

Example: CH3COOH.

Question 5

What does Ka measure?

Answer 5

Strength of an acid and its relative degree of dissociation

The greater the dissociation, the greater the concentration of products, so Ka increases.

Question 6

What does Le Chatelier’s principle state?

Answer 6

If a system in equilibrium is subjected to a change, the position of equilibrium will move to oppose the change

This principle is fundamental in understanding chemical equilibria.

Question 7

Local anaesthetics exist in equilibrium between which two forms?

Answer 7

• Non-ionised, fat soluble form
• Ionised, water soluble form

The fat soluble form is better able to diffuse into the neuron through the myelin sheath.

Question 8

What is the Henderson-Hasselbach equation used for?

Answer 8

To compare the relative strengths of acids

pKa is the pH at which exactly 50% of the local anaesthetic is in its weak acid or base form.

Question 9

At higher temperatures, how does pH affect the entry of local anaesthetics into cells?

Answer 9

pH decreases, leading to less un-ionised, fat soluble drug entering cells

In inflamed tissue, a reduced pH results in a greater proportion of the ionised drug.

Question 10

List some indications for local anaesthetics.

Answer 10

• ID block or buccal infiltrations
• 5% lidocaine topical gel
• 5% lidocaine cream for nervous patients
• Post-operative pain relief with longer-lasting LA

Examples of longer-lasting LA include bupivacaine or levobupivacaine.

Question 11

What are some side effects of local anaesthetics?

Answer 11

• Affects excitable membranes
• Cardiac arrhythmias
• CNS function suppression
• Mild vasoconstrictor or vasodilator activity

Allergy to LA is uncommon, especially with ester-based compounds.

Question 12

Where does the metabolism of local anaesthetics occur?

Answer 12

In the liver

Ester-containing LA can also be metabolised by plasma pseudo-cholinesterase.

Question 13

What is adrenaline also known as?

Answer 13

Epinephrine

It is an endogenous catecholamine secreted by the adrenal medulla.

Question 14

What are the effects of adrenaline dependent on?

Answer 14

The type of adrenoceptor that is bound

Adrenaline has different effects on alpha and beta receptors.

Question 15

What does the alpha 1 receptor do?

Answer 15

Causes vasoconstriction and raises blood pressure

It also aids in gluconeogenesis and increases plasma glucose concentration.

Question 16

What is the role of beta 2 receptors?

Answer 16

Causes bronchodilation and reduces airway resistance

This facilitates easier gas exchange.

Question 17

How is adrenaline metabolised?

Answer 17

• By Mono-Amine Oxidase (MAOs)
• By Catechol-O-methyltransferase

Some adrenaline is also excreted unchanged by the liver.

Question 18

What are some side effects of adrenaline in local anaesthetics?

Answer 18

• Palpitations
• Raised heart rate
• Anxiety
• Tremor

The effect is short-lived.

Question 19

Is adrenaline in local anaesthetics safe during pregnancy?

Answer 19

Yes, if clinically indicated

Elective treatment should be deferred unless urgent.

Question 20

A dentist administers lidocaine for a tooth extraction.
Explain step-by-step how lidocaine prevents pain transmission.

Answer 20

Step-by-step mechanism:
Lidocaine exists in ionised and non-ionised forms
The non-ionised (lipid-soluble) form diffuses across the nerve membrane
Inside the neuron, it becomes ionised
The ionised form binds to voltage-gated sodium channels
This blocks sodium influx
→ Prevents depolarisation
→ Action potential cannot propagate
→ Pain signal is not transmitted

Question 21

Why must a local anaesthetic enter the neuron before it can block sodium channels?

Answer 21

Local anaesthetic must enter the neuron because sodium channels are located on the inner side of the membrane. The non-ionised (lipid-soluble) form diffuses across the membrane, then becomes ionised inside the cell and binds to sodium channels, blocking depolarisation.

Question 22

A drug blocks sodium channels but cannot cross the cell membrane. Would it be effective?

Answer 22

No — it would not be effective.
Sodium channels are located on the inside of the neuron
The drug must enter the neuron to access and block them
If it cannot cross the membrane, it cannot reach its site of action
→ Therefore, it will not block action potentials

Question 23

A local anaesthetic exists in both ionised and non-ionised forms.
Which form:
Crosses the membrane?
Binds to the sodium channel?

Answer 23

Non-ionised form (lipid-soluble) → crosses the membrane
Ionised form (charged) → binds to the sodium channel
The nerve membrane is made of a lipid bilayer
→ Only lipid-soluble (non-ionised) molecules can diffuse through
Sodium channels are accessed from the inside of the neuron
→ The ionised form is the active form that blocks the channel

Question 24

A patient has an abscess (inflamed, acidic tissue). The local anaesthetic does not work well.
Explain why.

Answer 24

Inflamed tissue is acidic (low pH)
This shifts equilibrium towards the ionised form of the local anaesthetic
The ionised form cannot cross the nerve membrane
→ Less drug enters the neuron
→ Reduced sodium channel blockade
→ Poor anaesthetic effect

Question 25

If pH < pKa, which form predominates — ionised or non-ionised?

Answer 25

ionised form predominates ✅ Using Henderson-Hasselbalch: When pH is lower (more acidic) → more H⁺ present This pushes equilibrium toward the protonated (ionised) form 👉 For local anaesthetics (which are weak bases): Ionised form = LAH⁺ Non-ionised form = LA

Question 28

Why is **onset slower** in inflamed tissue?

Answer 28

More drug is ionised → less crosses membrane So it takes longer for enough drug to enter neurons → Slower onset and reduced effectiveness ## Footnote Inflammation affects the ionisation of drugs, impacting their ability to penetrate membranes.

Question 29

What are the **3 components** of a local anaesthetic and their roles?

Answer 29

* Aromatic ring: lipid solubility (helps membrane penetration) * Intermediate linkage (amide/ester): determines metabolism * Terminal amine: allows ionisation (important for binding) ## Footnote Each component plays a crucial role in the pharmacokinetics and pharmacodynamics of local anaesthetics.

Question 30

Amide vs ester metabolism — why does it matter?

Answer 30

* Amides (e.g. lidocaine): Metabolised in liver, longer duration * Esters: Broken down by plasma pseudocholinesterase, faster metabolism → shorter duration ## Footnote The metabolism pathway affects the duration of action and potential side effects of local anaesthetics.

Question 31

Why is **articaine different**?

Answer 31

Has a thiophene ring → increases lipid solubility Contains an ester group → can be metabolised in plasma → Faster breakdown + good penetration ## Footnote Articaine's unique structure contributes to its effectiveness and duration of action.

Question 32

Why do LAs cause **seizures** then **CNS depression**?

Answer 32

Initially block inhibitory neurons in CNS → Leads to uncontrolled excitation → seizures At higher levels: Suppress all neuronal activity → CNS depression (reduced consciousness, coma) ## Footnote The mechanism of action of local anaesthetics can lead to both excitation and depression of the central nervous system.

Question 33

Why can LAs cause **cardiac arrhythmias**?

Answer 33

Cardiac cells rely on sodium channels for conduction LA blocks these → disrupts electrical signalling → Arrhythmias, reduced contractility ## Footnote The impact on sodium channels is critical for cardiac function and can lead to serious complications.

Question 34

Why do LAs affect **multiple tissues**?

Answer 34

Because they act on all excitable membranes, including: * Peripheral nerves * CNS neurons * Cardiac muscle ## Footnote The broad action of local anaesthetics is due to their ability to interact with various types of excitable tissues.

Question 35

Why use **bupivacaine** post-op?

Answer 35

More lipid-soluble → stays in tissue longer Slower dissociation from sodium channels → Longer duration of analgesia ## Footnote Bupivacaine's properties make it suitable for prolonged pain relief after surgical procedures.

Question 36

Why are **amide allergies** rare?

Answer 36

They produce fewer antigenic metabolites compared to esters → Lower immune response ## Footnote The metabolic byproducts of amides are less likely to trigger allergic reactions.

Question 37

Why is **adrenaline** added to **LA**?

Answer 37

* Vasoconstriction (α1 receptors) * Reduces blood flow at injection site * Prolongs duration * Reduces systemic absorption ## Footnote Less drug enters circulation → ↓ toxicity.

Question 38

What are the receptor effects of **adrenaline**?

Answer 38

* α1 → vasoconstriction → ↑ BP * β1 → ↑ heart rate + contractility → ↑ cardiac output * β2 → bronchodilation → ↓ airway resistance ## Footnote These effects are crucial for understanding adrenaline's role in the body.

Question 39

Why do **palpitations** occur after LA with adrenaline?

Answer 39

* Adrenaline stimulates β1 receptors in the heart * Increased heart rate and force * Patient feels palpitations/anxiety ## Footnote This is a common side effect due to adrenaline's action on the heart.

Question 40

Why should caution be exercised in **cardiac patients** when using adrenaline?

Answer 40

* Increases heart rate * Increases blood pressure * Can worsen hypertension, arrhythmias, ischaemic heart disease ## Footnote Cardiac patients are at higher risk for complications.

Question 41

Why do **MAO inhibitors** increase adrenaline effects?

Answer 41

* MAO normally breaks down adrenaline * Inhibition → adrenaline lasts longer * Increased and prolonged effects ## Footnote This interaction can lead to heightened responses to adrenaline.

Question 42

Why should LA be avoided in the **1st & 3rd trimester** of pregnancy?

Answer 42

* 1st: risk to developing fetus * 3rd: effects on labour + circulation ## Footnote Caution is necessary to protect both mother and fetus.

Question 43

Is **adrenaline** safe in **pregnancy**?

Answer 43

Yes, in controlled doses if necessary ## Footnote Minimal transfer + short action makes it relatively safe.

Question 44

Explain why LA fails in an **infected tooth** and its management.

Answer 44

* Mechanism: Low pH → more ionised LA * Cannot cross membrane → Reduced effect * Management: Inject away from infection, use nerve block, increase dose safely ## Footnote Treating the infection first can improve LA effectiveness.

Question 45

How does **adrenaline** prolong LA and reduce toxicity?

Answer 45

* Vasoconstriction → ↓ blood flow * Slower removal of LA → longer duration * Less systemic absorption → ↓ toxicity ## Footnote This mechanism is essential for effective local anesthesia.

Question 46

Compare **normal vs inflamed tissue** regarding LA effectiveness.

Answer 46

* Normal: Higher pH, More non-ionised LA → Good penetration → effective * Inflamed: Low pH, More ionised LA → Poor penetration → ineffective ## Footnote Understanding tissue conditions is key for effective anesthesia.