Unit 1: Drug Biotransformation

Question 1

Molecules with a ______ charge are usually reabsorbed

Answer 1

Neutral

Question 2

Which organ excretes most drugs?

Answer 2

Kidneys

Question 3

Other drugs that are often reabsorbed are ________, aka “_______”

Answer 3

Lipophilic or “protein bound”

Question 4

What process changes drugs to allow for excretion?

Answer 4

Metabolism

Question 5

Name the factors that affect the rate of excretion from the kidneys:

1.
2.

Answer 5

1. Blood flow to the kidneys

2. GFR (glomerular filtration rate)

Question 6

What helps to get rid of drugs that are protein-bound?

Answer 6

OAT or OAC

Organic anion transporters
Organic cation transporters

Question 7

Remember: Lipophilic drugs can easily be ______ and therefore prevent excretion

Answer 7

Reabsorbed

Question 8

General changes during drug metabolism:

1.
2.
3.
4.

Answer 8

1. Active drug —> active metabolite
2. Active drug —> inactive metabolite
3. Pro-drug —> active drug
4. Active drug —> toxic metabolite

Question 9

Drug metabolism occurs in how many phases?

Answer 9

Phase I and Phase II

Question 10

Most biotransformation occurs when?

Answer 10

Between absorption into circulation and elimination

Question 11

What does Phase I do?

Answer 11

Converts drug to more polar metabolite

Question 12

Name some processes for Phase I:

Answer 12

Oxidation
Hydrolysis
Reduction

Question 13

What is the overall effect of Phase I on a drug?

Answer 13

Enhances water solubility

Question 14

Why do we need Phase II?

Answer 14

To further polarize metabolites so the kidney can excrete them.

Phase 2 processes add something to the drug to make it
Inactive
Polar
More readily excretable

Question 15

Name processes involved in Phase 2:

Answer 15

Acetylation
Methylation
Glucuronidation

Question 16

Where do phase I and phase II processes generally occur?

Answer 16

Rough endoplasmic reticulism

Question 17

Name 2 key enzymes in phase I reactions

Answer 17

P450 oxidoreductase

Cytochrome P450

Question 18

Where are the enzymes housed which perform oxidative drug metabolism?

Answer 18

In the smooth ER

Question 19

Abbreviations for Cytochrome P450

Answer 19

P450

CYP

Question 20

What genetic factors are important to remember with the CYP450 mechanism?

Answer 20

CYP2D6 for caucasians (deficient in some)

CYP2C19 for caucasians and Japanese (completely absent for some)

Question 21

Name most important family in CYP450 mechanism?

Answer 21

CYP3A4: responsible for 50% of drug metabolism by liver

Question 22

Effect of a CYP inducer:

Answer 22

Speed up metabolism of other drugs —> decreases effectiveness

Question 23

Effect of CYP or P450 inhibitor:

Answer 23

Blocks enzymes that metabolize other drugs —> increases potential for toxicity

Question 24

Phase II reactions are

 Faster or Slower?

than P450 catalyze reactions

Answer 24

FASTER

Question 25

Diseases that affect drug metabolism

Answer 25

Anything that affects the liver: hepatitis, cirrhosis
Cardiac disease or renal disease that affects blood flow to liver
Hypothyroidism: increases half life of some drugs
Hyperthyroidism does the opposite

Question 26

Phase I enzymes are involved in the biotransformation of ____% of prescription drugs

Answer 26

75%