Drug Metabolism

Question 1

types of oxidation reactions

Answer 1

hydroxylation, S-oxidation, N-oxidation, N-dealkylation, O-dealkylation

Question 2

drugs for hydroxylation

Answer 2

midazolam, propranolol

Question 3

drugs for S-oxidation

Answer 3

cimetidine

Question 4

drugs for N-oxidation

Answer 4

diphenhydramine

Question 5

drugs for N-dealkylation

Answer 5

methylxanthines (caffeine/theophylline), diazepam

Question 6

drugs for O-dealkylation

Answer 6

codeine–>morphine (activating)

Question 7

CYP-independent oxidations

Answer 7

1. ethanol and dehydrogenases
2. biogenic amines and MAO
3. hydrolases
4. hydrolysis

Question 8

hydrolytic rxns meaning

Answer 8

addition of water (hydrolysis) or epoxide detoxification

Question 9

SAGGMeth

Answer 9

1. sulfation
2. acetylation
3. glucuronidation
4. glutathione
5. methylation
   covalently conjugate drug at reactive center to make drugs POLAR

Question 10

sulfate conjugation

Answer 10

sulfotransferases, need activated sulfate, cytosolic

Question 11

acetylation

Answer 11

n-acetyl transferases, need acetyl CoA, makes drugs less polar?, cytosolic

Question 12

glucuronidation

Answer 12

glucuronyl transferase (UGT), need UDP glucuronic acid, smooth ER

Question 13

glutathione

Answer 13

glutathione s transferase (GST), protect against toxic metabolites, substrates = electrophiles, GSH for epoxides

Question 14

methylation

Answer 14

methyltransferases, cytosoloic enzymes, SAM

Question 15

acetominophen toxicity

Answer 15

CYPs can lead to toxic electrophile that can be rescued by GSH (glutathione) or kill liver cells if conjugated with macromolecules. NAC (n-acetylcystein) can be antidote

Question 16

most common polymorphism

Answer 16

CYP2D6

Question 17

CYP2D6 substrates

Answer 17

drugs to treat CNS disorders (antidepressants, antipsychotics, amphetamines, opioids)

Question 18

poor metabolizers of CYP2C19

Answer 18

asians who can’t metabolize diazepam or omeprazole

Question 19

substrates of CYP2C9

Answer 19

warfarin, NSAIDS

Question 20

substrates of CYP2C19

Answer 20

diazepam, omeprazole

Question 21

substrates of CYP2D6

Answer 21

codeine, CNS drugs, metroprolol

Question 22

substrates of CYP2E1

Answer 22

acetominophen toxicity, ethanol uses and induces

Question 23

ethanol acetominophen toxicity

Answer 23

ethanol induces CYP2E1 and deletes glutathione

Question 24

renal secretion interactions w drugs

Answer 24

probenecid/penicillin and digoxin/quinidine

Question 25

tenofavir in renal excretion

Answer 25

can build up toxic metabolites, probenecid can prevent that in proximal tubule while ritonavir can lessen efflux to cause toxicity

Question 26

high extraction drugs

Answer 26

flow limited

Question 27

low extraction drugs

Answer 27

limited by intrinsic hepatic metabolic capacity and fraction of free drug (unbound to protein)

Question 28

drugs recycled by enterohepatic circulation

Answer 28

digoxin, morphine, estradiol

Question 29

Vd

Answer 29

dose/[plasma]

Question 30

CL

Answer 30

volume of plasma getting cleared of drug per unit time, L/h or mL/min

Question 31

rate of elimination

Answer 31

amount of drug removed per unit time, mg/hr, = CL * [plasma]