Drug metabolism

Question 1

Lipophilic drug

Answer 1

Drugs can access tissues by diffusing across membrane (therapeutic effect)

Question 2

Water soluble drug

Answer 2

Drug retained in blood (less tissue access so faster clearance from system) and delivered to excretion sites
-lipid soluble drugs metabolised to water soluble drugs for easy excretion (metabolism aims to alter drug to make it less lipid soluble)

Question 3

Biochemical reactions in drug metabolism

Answer 3

Phase 1-> introduces reactive group to drug (increase polarity)
Phase 2-> add water soluble conjugate to reactive group

Question 4

Phase 1 metabolism

Answer 4

• oxidation/reduction creates new functional groups
• hydrolysis unmasks functional groups

FUNCTIONAL GROUPS SERVE AS ATTACHMENT POINT FOR PHASE II REACTIONS

Question 5

Phase 2 metabolism

Answer 5

• glutathione conjugation
• sulfation
• glucuronidation
• acetylation
• methylation
• amino acid conjugation

Question 6

Most common phase 1 metabolism reaction

Answer 6

Oxidation

Question 7

Most common phase 2 metabolism reaction

Answer 7

Glucuronidation

Question 8

Glucuronidation

Answer 8

• phase 2 metabolism reaction
• low affinity
• high capacity (more likely to occur at high drug dosages)

Question 9

Sulfation

Answer 9

-phase 2 metabolism reaction
-high affinity/low capacity-> more likely to occur at low drug dosages
-opposite of glucurodination
-example: sulfation of low dose paracetamol
R-OH + PAPS-> R-O-SO3^- + PAP
-as paracetamol dose increases, phase 2 metabolism reaction switches to glucuronidation

Question 10

Glutathione conjugation

Answer 10

-electrophilic drugs needed in order to be conjugated or biotransformed to an electrophilic conjugate
Example: R-X + GSH-> R-SG + H-X