pharmacophore

Question 1

what is a pharmacophore?

Answer 1

An ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response

Question 2

what do new local anaesthetics (spacer) consist of?

Answer 2

Ionisable moiety (tertiary amine)
Lipophilic moiety (aromatic group)
Spacer

Question 3

what is the function of a local anaesthetic

Answer 3

Retain nerve blocking properties while eliminating CNS activity

Question 4

what are the features of an ester type local anaesthetic?

Answer 4

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

Question 5

give an example of an ester type local anaesthetic?

Answer 5

procaine

Question 6

what are the features of an amide type local anaesthetic?

Answer 6

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

Question 7

give an example of an amide type local anaesthetic?

Answer 7

lidocaine

Question 8

what are the features of lidocaine?

Answer 8

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

Question 9

what are the features of procaine?

Answer 9

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

Question 10

what is the difference between properties of esters and amide type local anaesthetics?

Answer 10

ester type-
metabolism: rapid in plasma cholinesterase
systemic toxicity: less likely
allergic reaction: possible- PABA derivatives
stability in solution: breaks down
onset of action: slow
pKa’s value: higher than pH

amide type-
metabolism: slow-hepatic
systemic toxicity: more likely
allergic reaction: very rare
stability in solution: very stable chemically
onset of action: moderate to fast
pKa’s value: close to pH

Question 11

how do local anaesthetics block nerve impulses?

Answer 11

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)

Conduction of nerve impulses is mediated by action potential, identified by accumulation of cations inside of the neurons