Review of Pharmacokinetics

Question 1

• unique pharmacokinetics of large molecules:
• ______ administration
• slow tissue distribution leading to ________ kinetics
• variable half lives, -mabs have long half life
• unique adverse effect profile

Answer 1

parenteral

multi compartment

Question 2

for 2 drugs to be _______, Cmax, Tmax, and AUC must be equivalent

Answer 2

bioequivalen

Question 3

strongly plasma protein bound drugs and very large drugs (heparin) distribute in?

Answer 3

plasma water (3 Liters in 70 kg man)

Question 4

large water soluble drugs such as mannitol distribute in?

Answer 4

extracellular water (0.2 L/kg)

Question 5

small water soluble drugs such as ethanol distribute in ?

Answer 5

TBW (0.6 L/kg)

Question 6

drugs that avidly bind tissues such as chloroquine distribute in?

Answer 6

tissue concentration (>0.7 L/kg)

Question 7

main enzyme for metabolism of 50-60% of current drugs? extensively expressed in GI cells and liver, often responsible for first pass

Answer 7

CYP3A4

Question 8

phenobarbital, phenytoin, carbamezepine, rifampin enzyme induction?

Answer 8

CYP2C9, CYP2C19

Question 9

glucocorticoids, anticonvulsants, rifampin, St Johns wort enzyme induction?

Answer 9

CYP3A4

Question 10

isoniazid, chronic alcohol, carcinogenic nitrosamines enzyme induction? importnat for acetaminophen toxicity

Answer 10

CYP2E1

Question 11

phenobarbital, primidone, phenytoin, carbamezepine, rifampic, polycyclic chemical, glucocorticoids, chornic alcoho and St Johns wort and key _______ of metabolism

Answer 11

inducers

Question 12

cimetidine, erythromycin, ketoconazole, chloramphenicol, disulfiram, acute alcohol, and grapefruit juice are key _______ of metabolism

Answer 12

inhibitors

Question 13

warfarin:
- deficiency of CYP2CP ______ biological effect
- mutation in VKORC1 ________ biological effect

Answer 13

increases

decreases

Question 14

isoniazid for TB:

• ADR leads to ________
• gene: N-acetyltransferase

Answer 14

hepatotoxicity, neurotox

Question 15

mercaptopurine for ALL:

• ADR hematological toxicity
• gene:

Answer 15

thiopurine S-methyltransferase

Question 16

irinotecan for chemo of colon cancer:

• ADR: _______
• gene: UGT1A1

Answer 16

diarrhea, neutropenia

Question 17

codeine as analgesic:

• response: lack of analgesic effect
• gene:

Answer 17

CYP2D6

Question 18

oxidation, redution, hydrolysis are phase _____ metabolism, which change structure

Answer 18

phase 1

Question 19

phase 2 metbolism involves _______ which adds a group

Answer 19

conjugation

Question 20

glucoronidation, sulfate conjugation, and glycine conjugation make drugs more ______ soluble

Answer 20

water

Question 21

acetylation, methylation make drugs more ______ soluble

Answer 21

lipid

Question 22

_______ conjugation detoxifies reactive chemicals and reactive oxygen species

Answer 22

glutathione

Question 23

secretion of anions blocked by _______, secretion of cations blocked by _______

Answer 23

probenicid

N-methyl-NAD