19.5 Drugs affecting nerve excitability

Question 1

What is the difference between:

analgesic

local anaesthetic

general anaesthetic?

Answer 1

Analgesic: targets pain/sensory pathways

Local anaesth: regionalised inhibition of pain/sensory pathways, (no LOC)

General anesthetic:
depresses cortical processing of pain/sensory signal (LOC, systemic)

Question 2

What type of drug is cocaine? What does it do?

Answer 2

Active alkaloid, NA uptake inhibitor and CNS stimulant

Question 3

How do local anesthetics work?

Answer 3

Reversibly block conduction (selective Na+ binding) of nerve impulses at axonal membrane

Question 4

What are the differences between local anasthetic (weak bases):

aminoesters:

aminoamides

benzocaine

Answer 4

aminoesters: procaine (shorter acting, hydrolysis by esterases)
aminoamides: lignocaine, bupivicaine, ropivicaine (longer acting, hepatic metabolism)
benzocaine: weak… (lozenge)

Question 5

Do local anasthetics affect all or some nerves? Are they safe?

Answer 5

All nerves (peripheral, autonomic, heart)

Considered safe

Question 6

In local anaesthetics e.g. an epidural, is there greater motor or sensory block sensitivity?

Answer 6

Greater sensory block sensitivity

Question 7

Where is the site of action of local anaesthetics?

Answer 7

Bind inside Na+ channel (membrane interaction)

Question 8

What local anaesthetics work by:
hydrophobic

hydrophilic

mechanisms? What is the difference between them?

Answer 8

Hydrophobic: benzocaine (fast, non use dependent)

Hydrophilic: aminoesters/amides (slow, use dependent)

Question 9

Is there a RMP change with local anaesthetics?

Answer 9

No change in RMP, they stabilise the axon membrane

Question 10

What are the side effects of local anaesthetics that are proportional and not proportional to blood level?

Answer 10

Proportional: CV (depression), CNS (excitation)

Not proportional: Hypersensitivity reactions

Question 11

How do benzos work?

Answer 11

Enhance GABA (inhibitory) input

Question 12

How does e.g. phenytoin work?

Answer 12

Reduced excitatory input (glutamate)

Question 13

What are 2 theories of the mechanism of action as how the pharmacodynamics are affected with general anaesthetics

Answer 13

1. Lipid theory (potency and lipid solubility)

2. Receptor interaction (inhibition of excitatory R’, enhance inhibitory R’)