BMP: drug design 7

Question 1

What is a pharmacophore?

Answer 1

Part of a molecular structure responsbile for the pharmacological or biological effects

Question 2

What is the difference between local anaesthesis and anasethesia

Answer 2

Local anaesthisa is complete loss of sensation in a defined region in the body due to a pharmalogical agent. There is no loss of conscousness

Anaesthesia is the complete loss of sensation over the whole body due to a pharmaolgical agent. Unconsciousness occurs. Usually induced by IV then maintained by inhalayion

Question 3

What does the log P tll us about the type of LA

Answer 3

Log P above 2 it can penetrate the BBB thereofre is total A. Below is Local

Question 4

What was the first ester and first amide LA?

Benefit and negative of ester as opposed to amide?

Answer 4

• Procaine
• Lidocaine
• Stronger bases, less stable to heat

Question 5

What are examples of tropaine alkaloids?

Answer 5

• Atropine
• Hyosaine
• Ecgonine

Question 6

What structures are present in an LA?

Answer 6

• ionisable group (tertiary amine)
• Linker/ spacer (ester or amide)
• Lipophillic group (aromatic)

Question 7

Discuss Procaine properties

Answer 7

• Ester LA
• Comparable activity as cocaine
• Non-addicitive
• Metabolised to p-aminobenzoic acid
• Inherent instability due to ester bond
• Short half life
• P-amino benzoic acid responsible for allergic reactions

Question 8

Describe the properties of lidocaine

Answer 8

• 10 fold more active that cocaine
• Rapid onset of action
• Heat stable / higher chemical and thermal stability
• Non-allergic
• Longer half life
• No metabolism to p-aminobenzoic acid

Question 9

Comparision of Easter vs Amide properties:

Answer 9

Question 10

What are the 3 theories of how LAs work?

Answer 10

1. Membrane expansion: Free base dissolves in the phopholipid membrane of neurons and causes expansion and disrotion of the membrane. LEads to blockage of Na+ channels
2. Membrane surface changes: The cationic form of the LA positions itself on the surface of the cell membrane of neurons and neutralises its negtaive charge
3. LA receptor: LA enters cell membrane in unionised form and beocmes ionised in the neuron. It binds to the intracellular receptor which then blocks Na+ channels thereofre entery of Na+