W19-L5: Regulating Neuronal Excitability

Question 1

Analgesics

Answer 1

Targets pain/sensory pathways

Question 2

Local anaesthesia

Answer 2

Regionalised inhibition of pain/sensory pathways (primary afferent nerves) with no loss of consciousness

Question 3

General anaesthesia

Answer 3

Depresses cortical processing of pain/sensory signals which is not regionalised with loss of consciousness (stops processing)

Question 4

Local Anaesthetic Agents

Answer 4

Weak bases that reversibly block conduction of nerve impulses at the axonal membrane by interfering with influx of Na+, which differ in onset, duration and toxicity

Question 5

Aminoesters

Answer 5

Local anaesthetics eg procaine

•Shorter acting, hydrolysis by esterases

Question 6

Aminoamides

Answer 6

Local anaesthetics eg lignocaine, bupivicaine, ropivicaine

•Longer acting, hepatic metabolism

Question 7

Lethal toxins

Answer 7

-tetrodotoxin (puffer fish)

– saxitoxin (dinoflagellates)

Question 8

Benzocaine

Answer 8

in its own group of local anaesthetics

Question 9

Clinical use of local anaesthetics is considered safe because

Answer 9

• selective binding to Na+ channel
• reversible binding with no nerve damage
• will affect all nerves / excitable tissue
• Local application to limit systemic distribution

Question 10

Sensitivity of Nerves to Local Anaesthetics

Answer 10

non selective for a nerve type, by blocking sensory nerves you will also get motor nerves blocked too, which increases as you block more of the sensory nerves

Question 11

Where do local anaesthetics bind

Answer 11

Transmembrane domain which is intracellular

Question 12

Where do toxin bind

Answer 12

extracellular domains

Question 13

Hydrophobic mechanism for Local Anaesthetics

Answer 13

fast, non use dependent
- eg benzocaine
drug is usually in mainly non-ionised form and doesn’t allow the channel to conduct Na

Question 14

Hydrophilic mechanism for Local Anaesthetics

Answer 14

slow, use dependent - eg aminoesters & aminoamides
intracellular environment promotes charged form and in the charged form it requires the channel to be open to access the binding pocket

Question 15

General properties of local anaesthetics

Answer 15

• prevent propagation of nerve action potential
• small fibres more sensitive - (sensory > ANS > motor)
• stabilize axon membrane
• no change in resting membrane potential
• effect more pronounced in basic medium
• greater effect at high frequency

Question 16

Local Anaesthetic Toxicity

Answer 16

Proportional to blood level are CV eg hypotension (except cocaine) and CNS, not proportional are allergic reactions

Question 17

How many stages are there of general anaesthetics and what are they called?

Answer 17

Stage 1
Stage 2: Excitement
Stage 3: Surgical anaesthesia
Stage 4: Medullary depression

Question 18

General anasethetics side effects

Answer 18

Respiratory eg impaired ventilation, retention of secretions (anti-muscarinics are used) and cardiovascular eg cardiac arrythmias

Question 19

General Anaesthetics Theories on Mechanism of action

Answer 19

Lipid theory: Close correlation between anaesthetic potency and lipid solubility

Receptor Interaction:
Many anaesthetic agents inhibit excitatory receptors (glutamate, NMDA) and enhance effects on inhibitory receptors (GABA, glycine)