Metabolism and Excretion

Question 1

metabolism

Answer 1

administered drug is biochemically altered producing a metabolite - sometimes has activity. 75% of drugs undergo

Question 2

Excretion

Answer 2

removal of the drug from the body. kidney is the primary excretion organ for drugs. drugs can be eliminated through the bile or pulmonary route

Question 3

drug is renally excreted

Answer 3

unchanged parent drug eliminated this way. 25% of drugs undergo

Question 4

prodrug

Answer 4

biochemically activated through the body

Question 5

purpose of drug metabolism

Answer 5

inactivate a drug molecule and make it more hydrophilic - make it more polar to increase the polarity by introducing H bonding

Question 6

functional group modifications can be done to accomplish this

Answer 6

dealkylation, oxidation, all metabolism pathways

Question 7

hepatocyte - how can drugs enter? (2)

Answer 7

cell type in the liver responsible for drug metabolism. 1. passive diffusion 2. carrier transporters

Question 8

OATP inhibitor

Answer 8

plasma levels will go up- keep the drug from getting from blood to the hepatocyte.

Question 9

phase 1 hepatic metabolism

Answer 9

introduce or expose a functional group to increase polarity EX: oxidation, hydroxylation, hydrolysis

Question 10

phase 2 hepatic metabolism

Answer 10

1. Conjugating reactions

2. When we are adding a large functional group - hydrophilic

Question 11

cytochrome p450 enszymes

Answer 11

ox/redox reactions and hyrolysis. steroids, fatty acids, prostaglandins, bile acids. critical in removal of drugs, carcinogens, insecticides, plant toxins and enviromental pollutants

Question 12

Cytochromes: substrates drugs and other xenobiotics (coming outside the body , toxic)

Answer 12

CYP1, CYP2, CYP3

Question 13

Cytochromes: substrates fatty acids, prostaglandins, thromboxanes

Answer 13

CYP4, CYP5, CYP8

Question 14

Cytochromes: substrate steroid hormones

Answer 14

CYP7, CYP11, CYP17, CYP21, CYP24, CYP27

Question 15

factors influencing activity: nutrition

Answer 15

grape fruit juice 3A4 inhibitor - statins metabolized by 3A4 - you would have a higher than expected level if you drink grape fruit juice while taking statins (1A1, 1A2, 2E1, 3A3, 3A4,5)

Question 16

factor influencing activity: smoking

Answer 16

smoking induces 1A2 - smoker would need a higher dose even if hydrocarbons in food can go up - decreases the effect (1A1)

Question 17

factor influencing activity: Alcohol

Answer 17

2E1, chronic ethanol intake the effect of the drug would be lower so you will need a higher dose

Question 18

factor influencing activity: environment

Answer 18

1A1, 1A2, 2A6, 1B, 2E1, 3A3, 3A4, 5

Question 19

factor influencing activity: drugs

Answer 19

1A1, 1A2, 2A6, 2B6, 2C, 2D6, 3A3, 3A4, 5

Question 20

factor influencing activity: genetic polymorphism

Answer 20

NO 3A4,5!!! but! 1A, 2A6, 2C9, 19 ; 2D6, 2E1

Question 21

phase 2 reactions

Answer 21

involve attaching hydrophilic/polar molecule to a drug. independently of P450 enzymes or after P450 has metabolized to the drug. always inactivates the parent drug molecule but some instances where a phase 2 metabolite could still have activity.

Question 22

glucuronidation

Answer 22

deconjugating:b-glucuronidase, morphine, valpuric acid, more hydrophillic,
phase 2
enzyme: UGT
Co-sub: UDPGA

Question 23

sulfation

Answer 23

deconjugating enzyme: sulfatase, 
enzyme: sulfotransferase, 
co-sub: PAPS
more hydrophilic
phase 2

Question 24

glutathione conjugation

Answer 24

deconjugating enzyme: acetaminophen
enzyme: GST
co-sub: GSH
phase 2

Question 25

amino acid conjugation

Answer 25

glycine, glutamine, aspartic acid, serine
deconj enzyme: amidase
enzyme: N-acyltransferase
phase 2

Question 26

acetylation

Answer 26

less hydrophilic
co-sub: acetyl-coA
enzyme: NAT
deconj enzyme: amidase