Anaesthesia, analgesia and opioids

Question 1

How do local anaesthetics affect neurons?

Answer 1

They target voltage-gated sodium ion channels (VGSCs), reducing Na⁺ entry into axons → Prevents sequential channel opening needed for depolarisation.

Question 2

Why do local anaesthetics primarily target nociceptive neurons?

Answer 2

Aδ & C fibres have small diameters, increasing drug sensitivity → Local application ensures selectivity.

Question 3

What are the clinical benefits of local anaesthesia over general anaesthesia?

Answer 3

Increased patient safety, allows outpatient surgical procedures, minimizes systemic effects

Question 4

What role do Na⁺ and K⁺ channels play in action potentials?

Answer 4

• Rapid Na⁺ influx → Depolarisation.
• K⁺ efflux → Repolarisation and return to resting potential

Question 5

What are the depolarisation thresholds for VGSC gating?

Answer 5

1. Resting (-70 mV): m-gate closed, h-gate open.
2. Active (-50 mV): Both gates open → Na⁺ influx.
3. Inactivated (-20 mV): m-gate open, h-gate closed → Prevents reopening.

Question 6

What restores ion channel conformation after action potential?

Answer 6

K⁺ efflux repolarises membrane (-70 mV) → m-gate returns to closed state, h-gate reopens.

Question 7

How do local anaesthetic drugs enter the axon?

Answer 7

• Lipid-soluble free base penetrates membrane.
• Protonated inside the axon → Binds to inactivated VGSC state, preventing reopening.

Question 8

What happens when enough VGSCs are blocked?

Answer 8

Membrane potential falls below depolarisation threshold, preventing action potentials → Loss of sensation.

Question 9

What determines the effectiveness of local anaesthetics?

Answer 9

1. Lipid solubility → Influences tissue penetration.
2. Binding preference for inactivated channels → Use-dependence enhances efficacy in highly active neurons

Question 10

What are the three key chemical regions of local anaesthetics?

Answer 10

1. Lipophilic region (aromatic) → Penetrates membrane.
2. Hydrophilic region (amine group) → Protonation allows activation inside axon.
3. Ester/amide linker → Influences metabolism & duration

Question 11

How do local anaesthetics block ion channels?

Answer 11

Bind to inactivated VGSC state, preventing transition back to resting conformation.

Question 12

What are commonly used local anaesthetics?

Answer 12

• Lidocaine, prilocaine, articaine → Rapid onset, short-medium duration.
• Bupivacaine → Slow onset, long duration, used for epidurals in labour and surgery.

Question 13

What is the main side effect of local anaesthetics?

Answer 13

Cardiovascular effects due to off-target VGSC block, minimized by localized delivery

Question 14

How do general anaesthetics differ from local anaesthetics?

Answer 14

• Local anaesthetics target VGSCs → Prevent action potentials locally.
• General anaesthetics reduce synaptic transmission across CNS → Loss of consciousness.

Question 15

What is the correlation between general anaesthetics and lipid solubility?

Answer 15

Higher lipid solubility enhances CNS penetration, increasing effectiveness

Question 16

What are key risks of general anaesthesia?

Answer 16

• Depression of cardiac & respiratory function.
• Narrow therapeutic window → Dose precision required.

Question 17

What drugs are used in a typical in-patient surgical procedure?

Answer 17

1. Pre-med anxiolytic (e.g., benzodiazepine/barbiturate).
2. Injected anaesthetic (e.g., propofol → Rapid induction).
3. Peri-operative opioid analgesic (e.g., alfentanil).
4. Inhaled general anaesthetic (e.g., isoflurane).
5. Neuromuscular blocker (e.g., tubocurarine).
6. Antiemetic (e.g., ondansetron).
7. General muscarinic antagonist (e.g., atropine).
8. Acetylcholinesterase inhibitor (e.g., neostigmine) → Reverses neuromuscular blockade post-surgery.
9. Post-operative opioid analgesic (e.g., morphine).

Question 18

Why must patients be closely monitored during general anaesthesia?

Answer 18

To prevent overdose, maintain airway function, manage cardiovascular risks