L4 - Drug Target Pharmacodynamics - Part 2

Question 1

WHat is special about the amino acids that borer the active site in COX

Answer 1

• produce a particular 3D-shape that maximised interactions between the enzyme and the substrate
• these interactions ensure that the substrate is held in the correct position so that reaction can be catalysed
• can expand and contract to allow subsrates in and out
  
  • lowers activation energy
  • forces substrate into a transition-state conformation

Question 2

interactions between COX and substrate

Answer 2

• mixture of H-bonds
  
  • which are directional and specific for H-bonding groups on the substrate
  • point directly at eachother
• short-range van der Waals interactions between the surface of the substrate and the surface of the active site

Question 3

How do NSAIDs inhibit COX

Answer 3

• flurbiprofen is a competive inhibtor of cox enzymes
• binds in preference to arachidonic acid
  
  • therefore blocking prostaglandin syntehesis which reduces the inflammatory response
• some structural resembelance to match the 3D shape of the active site
• to compete effectively, must form stronger interactions with active site
  
  • binds in preferance to substrate
• binding process is dynamic
  
  • molecules will associate and dissociate regularly#
  • inhbitors need to stay in longer than the substrate to be effective

Question 4

What are the features of flurbiprofen that allow it to have a stronger affinity?

Answer 4

• additional pi-cation interaction between the phenyl ring electron cloud and the positively charged Arg 120 side chain
  
  • absent in substrate

Question 5

WHat is the difference in the structures of salbutimol and adreanaline which allow it bind more effectively?

Answer 5

*

Question 6

pharmacodynamics

Answer 6

• what the drug does to the body
  
  • the therapeutic effect of the drug
  • how it exerts its effect
  • how it interacts with the target

Question 7

pharmokinetics

Answer 7

• what the body does to the drug
  
  • how well it is absorbed into the body
  • where it goes to in the body
  • how long it stays in the bod
• small changes causes changes in the pharmokinetic action of a drug
  
  • e.g. absorbtion, CNS penetration

Question 8

what is the problem with changing a drugs function group to modify pharmacodynamic effects

Answer 8

• will also affect its pharmacokinetic profile and vice versa
• physiochemical properties facilate absorbtion via oral administraon
• function group modifications can control metabolism and half-life