Lecture 7

Question 1

what is a pharmacophore?

Answer 1

an ensemble of steric and electronic features that are necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger/block its biological response.

Question 2

what is anaesthesia and what is it characterised by?

Answer 2

a state of drug-induced absence of perception of all sensations.

it is characterised by unconsciousness, analgesia, amnesia and muscle relaxation

usually induced with intravenous anaesthetics and maintained with inhalation anaesthetics.

Question 3

what is local anaesthesia?

Answer 3

a state of drug induced absence of local nerve impulse transmissions (analgesia) in the region it is applied without loss of conciousness.

Question 4

design of new local anaesthetics

Answer 4

• tertiary amine group
  -aromatic group
• spacer
• retain nerve blocking properties while eliminating CNS activity.

(procaine and lidocaine)

Question 5

what is an example of an ester-type local anaesthetics?

Answer 5

procaine

Question 6

procaine features

Answer 6

• comparable activity as cocaine
• non-addictive
• metabolised to p-aminobenzoic acid

Question 7

ester-lype LA features

Answer 7

• inherent instability due to ester bond
  -short half life
  -p-aminobenzoic acid responsible for allergic reactions

Question 8

what is an example of an amide-type local anaesthetic?

Answer 8

lidocaine

Question 9

lidocaine features.

Answer 9

• 10 fold more active than cocaine
• rapid onset action
• heat stable
• non-allergenic

Question 10

amide-lype LA features

Answer 10

-higher chemical and thermal stability
- longer half life
- no metabolism to p-aminobenzoic acid

Question 11

membrane expansion

Answer 11

disruption of the topology of the cell membrane of the neurones by the free base form of LA.

Question 12

membrane surface charge

Answer 12

the cationic form of LA positions itself on the surface of the cell membrane of the neurones and neutralises its negative charge

Question 13

local anaesthetic receptor

Answer 13

intracellular receptor that mediates disruption of nerve signal when it is complexed with a LA

Question 14

Putative mechanism of action

Answer 14

-Conduction of nerve impulses is mediated by action potential, identified by accumulation of cations inside of the neurons
-Cationic form of anaesthetic binds at inner surface of Na+ channel – preventing Na+ influx (rising phase of membrane potential) which initiates action potential → blockade of nerve impulses (e.g., those mediating pain