19- sar part 5 metabolism

Question 1

what is phase i of metabolic stability

Answer 1

• Adds polar functional groups to reduce lipophilicity
• Oxidation
  
  • functional groups get added to make something more water soluble
• Hydrolysis
  
  • adding an ester or an amide to cut the molecule into smaller part

Question 2

what is phase ii of metabolic stability

Answer 2

Conjugation (add groups) to improve water solubility

Question 3

explain the example of CYP450 in phase i metabolism

Answer 3

• Oxidation of aliphatic or aromatic groups → at electron rich sites
• Cytochrome P450 contains a heme iron (it has 4 N atoms that hold it in place, which controls the oxidation states allowed for the O)

Question 4

what two cycles are used to oxidize iron inside drugs

Answer 4

NADP and NADPH

Question 5

explain the insertion step of the catalytic cycle of the enzyme

Answer 5

• take a H on the drug that is connected to some other atom (usually C), and you insert an oxygen in between the H and the C
• go from R-H to R-OH

Question 6

where does metabolism tend to happen in the molecule

Answer 6

electron rich areas (test this by formal charge)

Question 7

what does phase ii allow kidney to dispose of

Answer 7

• Glucuronic acid
• Sulfonation
• Acetylation
• Glutathione

Question 8

what are two common measurements of metabolism

Answer 8

• Liver microsomes
  
  • Half-life is measured (T1/2)
  • mix the drugs and the liver microsomes and measure the half life
• Plasma stability
  
  • T1/2
  • mix blood plasma and drug

Question 9

what are the eight effects of structure of molecular properties

Answer 9

• Potency
• Solubility
• Permeability
• pKa
• Melting point
• Bioavailability
• Metabolic Stability
• Chemical Stability