lecture 4 part 3

Question 1

name 3 body compartments into which the drug may be distributed

Answer 1

water
fat
bone

Question 2

what drugs will get distributed to:

-total body water
-extracellular water
-blood

Answer 2

blood = heparin, strongly plasma bound and large molecules

total body water = small, water soluble molecules like ethanol

extracellular water = large, water soluble molecules like gentamicin

Question 3

name drugs that will get distributed into the bone

Answer 3

certain ions like lead and fluoride

Question 4

what things will get distributed into the fat

Answer 4

highly lipid soluble molecules

Question 5

rank the following according to their Vd:

digoxin
acetaminophen
chloroquine

Answer 5

highest = chloroquine

digoxin

lowest = acetaminophen

Question 6

true or false

clearance is additive

Answer 6

TRUE

function of elimination by ALL participating organs like the liver and kidney

Question 7

name the 2 most important sites for drug elimination

Answer 7

liver and kidney

Question 8

what are the units for clearance

Answer 8

mL/min

Question 9

name the 2 main factors in renal excretion

Answer 9

-glomerular filtration
-passive tubular reabsorption

Question 10

true or false

if a drug is strongly bound to protein, it will be filtered

Answer 10

FALSE – it will not be filtered and will go back to the blood

Question 11

true or false

enhanced lipid solubility favors reabsorption

Answer 11

true

Question 12

give an example of a drug that is completely reabsorbed

Answer 12

thiopental and all barbiturates

Question 13

** name 4 things that affect renal tubular reabsorption rate

Answer 13

pH
pka compared to urine pH
weak acid or weak base
rate or renal tubular blood flow

Question 14

what does it mean if a drug is “transferred to glomerular filtrate?”

Answer 14

it is secreted out of the body

Question 15

true or false

when lipid soluble drugs are reabsorbed back into the body, the mechanism is through active transport

Answer 15

FALSE - passive

Question 16

how does chronic ethanol use affect metabolism

Answer 16

it induces CYP2E1

therefore, the effect of ethanol won’t happen (or not as much) because it gets metabolized quickly

Question 17

grapefruit juice

Answer 17

potent inhibitor of CYP3A4 (localized in intestinal wall mucosa)

Question 18

genetic polymorphism of CYP2D6

Answer 18

5-10% of caucasians are poor metabolizers but only 1-2% for asian population

Question 19

genetic polymorphism of CYP2C19

Answer 19

20% of asians are poor metabolizers and only 4% caucasian

Question 20

**** explain enterohepatic cycling and what xubstances go through it

Answer 20

glucuronide conjugates – hydrolyzed in GI back to the parent molecule.

parent molecule gets reabsorbed back into the body again and again – duration of action prolonged.

VITAMIN B12, VITAMIN D3, FOLIC ACID, ESTROGENS

Question 21

define half life

Answer 21

the time required to decrease the amount of drug in the bpdy by HALF during elimication

Question 22

explain what 1st order elimination is

Answer 22

a constant fraction of the drug dissapears from the body in an equal interval of time

Question 23

true or false

most elimination mechanism are through first order

Answer 23

true

Question 24

true or false

the concentration of drug in the plasma drops exponentially with time

Answer 24

true - 1st order kinetics

Question 25

explain zero order

Answer 25

elimination is constant and INDEPENDENT of drug concentration very few drugs eliminated this way

Question 26

true or false disease states do not affect half life

Answer 26

false -- they do bc disease states affect clearance and VD

Question 27

**** what is the average amount of half lives for a drug to be fully excreted

Answer 27

around 7

Question 28

one half life will reduce the drug by 50% how much drug will be remaining after 2 half lives?

Answer 28

25%

Question 29

one half life will reduce the drug by 50% how much drug will be remaining after 5 half lives?

Answer 29

3.12%

Question 30

one half life will reduce the drug conc in the body to 50% how many half lives are needed to get to 12.5%?

Answer 30

3 half lives

Question 31

the half life is useful in estimating the time to reach......

Answer 31

steady state

Question 32

approximately ___ half lives are required to reach about ____% of a new steady state

Answer 32

4 half lives, 94%

Question 33

drug accumulation will be observed if...

Answer 33

the dosing interval is less than 4 half lives

Question 34

in the simplest case, drugs are directly related to.....

Answer 34

plasma concentration

Question 35

give reasons for delayed drug effects

Answer 35

the time required for the drug to distrubute from the plasma to the site of action slow turnover of physiologic substances involved in producing the drug effect warfarin inhibits vitamin k epoxidase in the liver. this forms a clotting complex with a long half life (14 hours)

Question 36

what is the "maintenance dose"

Answer 36

just enough drug is given in each dose to replace what has been eliminated since the preceding dose

Question 37

why might a loading dose be required?

Answer 37

to produce effective blood levels without delay

Question 38

loading dose formula

Answer 38

target concentration * VD /f f can be ignored if IV

Question 39

true or false the vd is different for every drug

Answer 39

true

Question 40

what is a useful indicator of renal function

Answer 40

creatinine clearance

Question 41

when drugs bind to tissues, is Vd higher or lower?

Answer 41

higher

Question 42

when drugs bind to plasma proteins, is vd higher or lower?

Answer 42

lower

Question 43

older people have decreased muscle mass and thus tend to have a _____ Vd of digoxin

Answer 43

smaller

Question 44

if a drug is highly lipid soluble, does vd increase or decrease? give an example

Answer 44

increase diazepam

Question 45

absorption usually occurs within the first _____ after a drug dose and varies according to food intake, posture, and activity

Answer 45

2 hrs