Drug metabolism & Biotransformation

Question 1

Most drugs/foreign compounds which get into the body are______soluble?When is exretion easiest?

Answer 1

• lipid
• when H2o soluble (prevents reabsorption from kidney tubules

Question 2

Where is metabolism mainly occurring? in what state are drugs more easily eliminated?

Answer 2

Liver cells (SER)

make drugs more polar so they are easier to eliminate

Question 3

What are 3 results of metabolism?

Answer 3

1. lipid soluble——>water soluble (all drugs)
2. active–>inacitve metabolite (most drugs)

inactive (codeine)—>active (morphine)

3. toxic—-> non-toxic

non-toxic—–>toxic (exAcetaminophen (tylenol))

Question 4

What are two ways that drugs get metabolized?

Answer 4

Phase I (uses enzymes-oxidases- to unmask or introduce polar groups) & Phase II (uses transferases to transfer endogenous polar molecules

Question 5

What does Phase I metabolism use?

Answer 5

P450 enzymes

Question 6

What does Phase II metabolism use?

Answer 6

transferases

-conjugation rxns-adding polar molecule

Question 7

What enzymes are included in the “cytochrome p450 family” and an example of non p450 enzymes?

Answer 7

1. heme containing enzymes
2. enzymes not selective–>cause drug interactions
3. CYP 3A4 (most common, met >50% of drugs)(3: family, A: subfamily, 4: isozyme)
4. CYP 2D6: famous for polymorphisms (ex codeine to morphine)
5. other non P450 phase I rxms (ex alcohol dehydrogenase)

Question 8

What are some substrate involved in Phase II metabolism? And some examples?

Answer 8

1. glucoronidation~25% drugs metabolised
   ex. morphine-6-glucuronide (more potent conjugate)
2. glutathione conjugation
   ex. acetaminophen metabolism (non-toxic)
3. acetylation
   ex. isoniazis acetylation (slow acetylators–>toxic effects)
4. sulfation
   ex. minoxidil (prodrug)–>minoxidil sulfate (vasodilator)
5. methylation
   ex. cathecholamines (dopamine, epi, norepi)