Exam II: Drug Metabolism

Question 1

Who performed the first biochemical study showing the passage of waste into urine (himself and his dog) in early 1880s?

Answer 1

Friedrich Wohler

Question 2

What are the possible outcomes of biotransformation

Answer 2

decrease in activity (detoxication)
increase in polarity
increase in activity/bioactivation (prodrug)
increase in toxicity (toxication)

Question 3

T/F a prodrug can be either lipid or water soluble

Answer 3

true

Question 4

do prodrugs increase or decrease bioavailability?

Answer 4

increase

Question 5

define xenobiotic

Answer 5

something not naturally produced by body (aka a drug)

Question 6

Who discovered the first class of antibiotics and which antibiotic was it?

Answer 6

Gerhard Domagk

sulfa drugs

Question 7

which organ is the main site of biotransformation?

where else does biotransformation occur?

Answer 7

liver

intestinal mucosa cells
renal tubular cells
other organs
colon (microbiota)

Question 8

Name the different metabolic pathways of phase I

Answer 8

oxidation
hydrolysis
reduction
add/expose functional group for phase II conjugation

Question 9

Name the different metabolic pathways of phase II

Answer 9

conjugative (inc mass and hydrophilicity)

Question 10

What makes newborns/infants metabolize drugs differently?
which phase II enzyme in particular?
why does chloramphenicol toxicity occur more in newborns?
why does bilirubin toxicity occur more in newborns?

Answer 10

• may not have developed all necessary enzymes for metabolism or not have enough enzymes to properly metabolize
• glucuronosyltransferases
• lack of glucuronidation
• lack of glucuronidation

Question 11

Which diseases primarily affect drug metabolism (organs/drugs)

Answer 11

liver disease
kidney disease
drug-drug interactions

Question 12

Which phase I enzyme do rats lack that is found in humans?

Answer 12

CYP3A4

Question 13

how can certain drugs affect other drug metabolism?

Answer 13

some drugs can induce/inhibit enzymes and thus reduce efficacy of another drug

Question 14

how can certain foods affect drug metabolism?

example with grapefruit:

Answer 14

some foods can inhibit drug enzymes

grapefruit juice can inhibit CYP enzymes

Question 15

Name the phase I hydrolysis enzymes

Answer 15

Carboxylesterase

Peptidase

Question 16

Name the phase I reduction enzymes

Answer 16

Azo-reductase   
carbonyl reductase
disulfide reductase
sulfoxide reductase
quinine reductase

Question 17

Name the phase I oxidation enzymes

Answer 17

Alcohol dehydrogenase
aldehyde oxidase  
Xanthine oxidase
monoamine oxidase
Diamine oxidase 
Cytochromes P450
Flavin monooxygenase

Question 18

What does hydrolysis do?

Answer 18

uses water to break chemical bonds

typically attacks oxygen and breaks the bond leaving OH

Question 19

what does oxidation do?

Answer 19

removes electrons and hydrogens from compound typically by adding something (mainly oxygen)

Question 20

what is N-demethylation

Answer 20

removal of methyl group (CH3) and replacing with a hydrogen on a nitrogen

Question 21

what does reduction do?

Answer 21

adds electrons and hydrogen to compound typically by removing something (mainly oxygen)

Question 22

Why is chloramphenicol toxic in newborns?

what syndrome does it cause?

Answer 22

they lack glucuronidation (phase II) enzymes

grey baby syndrome

Question 23

why does bilirubin toxicity occur in newborns?

Answer 23

they lack glucuronidation and develop temporary jaundice due to lack of excretion of bilirubin

Question 24

to be more easily excreted, acetaminophen turns into a sulfate by what process?

Answer 24

removal of OH replaced by sulfa group

Question 25

Define a genotoxic metabollite

Answer 25

compound that attaches to structures used for DNA causing mutations

Question 26

what is the chiral element in sulindac?

Answer 26

sulfur

Question 27

how are prodrugs activated? which enzymes are involved?

Answer 27

reduction

CYP1A2,3A4,1B1