module 3: first pass, phase i, and phase ii metabolism

Question 1

where is metabolism occurring?

Answer 1

liver -> hepatocytes -> smooth ER

Question 2

what is the path of blood supply to the liver during general metabolism?

Answer 2

liver -> inferior vena cava -> heart -> aorta -> celiac artery -> common hepatic artery -> liver

Question 3

what is first pass metabolism?

Answer 3

metabolism of a drug before it reaches the systemic circulation

Question 4

what are the two blood supplies to the liver?

Answer 4

hepatic artery
hepatic portal vein

Question 5

list the pathway of a pill being swallowed

Answer 5

intestines -> hepatic portal vein -> liver

Question 6

true or false: drugs given by mouth are not able to get to the rest of the body before they get metabolized and are subject to first pass metabolism

Answer 6

true

Question 7

true or false: rectal administration of a drug is subject to first pass metabolism

Answer 7

true

Question 8

list the pathway of a drug given rectally

Answer 8

rectum -> hepatic portal vein -> liver

Question 9

what are some administration pathways that won’t undergo first pass metabolism?

Answer 9

sublingual
IM

Question 10

what is bioavailability?

Answer 10

fraction of a drug given that reaches systemic circulation

Question 11

true or false: drugs with low bioavailability do not undergo first pass metabolism

Answer 11

false

Question 12

the intestines contain enzymes that help metabolize drugs and ________ bioavailability

Answer 12

reduce

Question 13

less drug absorbed means ________ plasma concentration

Answer 13

decreasing

Question 14

true or false: drugs that undergo first pass metabolism have decreased plasma

Answer 14

true

Question 15

metabolizing an active drug or molecule does what to it?

Answer 15

inactivates it

Question 16

what happens when the body thinks a drug is toxic?

Answer 16

metabolizes drug to make it non-toxic

Question 17

what is the drug called when given in its inactive form and becomes active once metabolized by the body?

Answer 17

pro drug

Question 18

whats an example of a pro drug turning into an active drug?

Answer 18

codeine -> morphine

Question 19

what is an example of a non toxic drug metabolizing to toxic?

Answer 19

acetaminophen -> hepatotoxic metabolites

Question 20

what happens when a lipid drug becomes metabolized?

Answer 20

becomes water soluble

Question 21

excretion is easiest when in what form?

Answer 21

water soluble

Question 22

what enzymes do phase I use?

Answer 22

CYP 450, oxidases (oxidation reactions, unmask O2)

Question 23

what does phase II use to metabolize?

Answer 23

conjugation reactions

Question 24

what is the function of oxidases?

Answer 24

to unmask or introduce polar groups (-OHs, -Os) on the drug

Question 25

what does cytochrome p450 do?

Answer 25

heme-containing enzymes that bind O2 and CO

Question 25

what does cytochrome p450 do?

Answer 25

heme-containing enzymes that bind O2 and CO

Question 26

when oxygen binds to the drug and water is also formed, where do the hydrogens come from?

Answer 26

NADPH

Question 27

where does NADPH come from?

Answer 27

by product from G-6-P----->G-PG (pentose phosphate shunt)

Question 28

how does NADPH act as a reducing agent?

Answer 28

it causes other molecules to get reduced and gain an electron and then as a result loses an electron, becoming oxidized which forms NADP+

Question 29

what is an example of a non-p450 phase I reaction enzyme?

Answer 29

alcohol dehydrogenase

Question 30

what is the purpose of alcohol dehydrogenase?

Answer 30

breaks down alcohol and takes it to form acetaldehyde (later broken down into acetate)

Question 31

what are the first and second most common cytochrome p450 enzymes?

Answer 31

CYP 3A4 and CYP 2D6

Question 32

explain the breakdown of the name CYP 3A4

Answer 32

3: family of drug A: subfamily of enzyme 4: isozyme

Question 33

what type of enzyme does phase II metabolism use and why?

Answer 33

transferases to attach small endogenous polar molecules to a drug (to make more water soluble)

Question 34

what are examples of polar molecules added to a drug through phase II metabolism?

Answer 34

glucuronate glutathione sulfate acetate

Question 35

what kind of reactions does phase II use?

Answer 35

conjugation

Question 36

what enzyme would be used to add acetyl to a drug?

Answer 36

N-acetyltransferase

Question 37

what is the purpose of adding an acetyl group to a histone?

Answer 37

increase gene transcription

Question 38

what are the most common conjugation reactions?

Answer 38

glucuronidation (most common) sulfation acetylation

Question 39

95% of tylenol is metabolized by _________ enzymes that form a non-toxic metabolite

Answer 39

phase II

Question 40

which phase I enzyme metabolizes over 50% of available drugs?

Answer 40

CYP 3A4

Question 41

which phase I enzyme is famous for polymorphisms (codeine)?

Answer 41

CYP 2D6

Question 42

what does the phase II enzyme UGT stand for and is responsible for what reaction?

Answer 42

UDP-glucuronosyltransferase -----> glucuronidation

Question 43

what does the phase II enzyme GST stand for and is responsible for what reaction?

Answer 43

glutathione-S- transferase ------> glutathione conjugation

Question 44

what does the phase II enzyme NAT stand for and is responsible for what reaction?

Answer 44

N-acetyltransferase ------> acetylation

Question 45

what does the phase II enzyme SULT stand for and is responsible for what reaction?

Answer 45

sulfotransferase -----> sulfation