Chapter 13 - Multiple Dosing

Question 1

what is the purpose of SINGLE DOSING and give an example

Answer 1

to get therapeutic drug concentrations for a short time

analgesic to treat an acute issue

Question 2

the purpose of _______ is to administer the drug usually on a chronic basis, to maintain therapeutic concentrations for prolonged periods

Answer 2

multiple dosing

Question 3

what is unique about the treatment interval of penicillins

Answer 3

it is DESIRED to have fluctuations between high and low levels of drug concentration with respect to MEC

Question 4

MOST DRUGS are dosed based on what?

Answer 4

at intervals of the drug’s half life

ie - if half life is 6 hours, we give the drug every 6 hours

Question 5

since we tend to give doses based on the half life, what does this mean about the amount of drug in the body?

Answer 5

since 1/2 is left in the body when we give the next dose, the amount accumulates in the body with each successive dose!

Question 6

a drug is continuously administered every 6 hours and at a dose of 500mg (same dose each time)

therefore, the extent of drug accumulation depends on what?

Answer 6

the dosing interval

Question 7

true or false

if the dosing interval is LESS than the half life, less drug will accumulate

Answer 7

FALSE - more drug accumulates

Question 8

what does the “tau” symbol represent

Answer 8

the dosing interval

Question 9

in normal doses, the tau should equal what value

Answer 9

the half life

Question 10

true or false

when the 1st dose of a drug is administered IV, the amount of drug in the body is EQUAL TO THE DOSE GIVEN

Answer 10

true

Question 11

half life = 6 hours
dose = 400mg

explain what happens after the 1st and 2nd dose

during the 2nd dose period, the amount of drug in the body ranges from ___ to ___

Answer 11

1st dose - 400mg in body

when 2nd dose is given, there is 200mg left and we are giving 400mg more. therefore, 600mg is in the body right after we give the 2nd dose

6 hours later - there is 300mg left in the body

300-600mg

Question 12

true or false

with each successive IV dose, the max amount of drug in the body is 100% of the previous increase

Answer 12

FALSE - 50% of the previous increase

Question 13

in which type of dosing are we concerned with steady state

Answer 13

multi dosing - not single dosing

Question 14

cmax is _________% of the ORIGINAL DOSE GIVEN

Answer 14

200%

Question 15

true or false

1st order elimination is INDPENDENT on concentration

Answer 15

FALSE - dependent on concentration

Question 16

give an example of when there would be NO ACCUMULATION

Answer 16

if the drug is given at a time when the previous dose has already undergone a lot of half lives (ie - 7)

if half life is 3 hours and we give another dose 24 hours later - no accumulation

Question 17

true or false

constant steady state of a chronic drug is desired

Answer 17

FALSE - we would get side effects this way

want fluctuation

Question 18

true or false

for each drug, the half life is constant even when given to patients with a different Vd

Answer 18

TRUE

just think of the half life formula — only depends on rate constant of elimination

Question 19

true or false

Vd is not constant for each patient - it changes

Answer 19

FALSE - constant to each patient

Question 20

when a drug is given at the same interval as the half life,

50% is _______ and 50% is _______

Answer 20

50% of each dose is ELIMINATED between doses and 50% of the dose accumulates

Question 20

the concentration of drug in the body depends on these 3 factors….

Answer 20

persistence factor
loss factor
accumulation factor

Question 21

define persistence factor

Answer 21

the amount of each dose that persists in the body during multiple dosing (fraction that was NOT ELIMINATED)

Question 22

true or false

elimination from the body is a zero order process

Answer 22

FALSE - 1st order

Question 23

true or false

the persistence factor cannot be determined from the 1st order rate equation

Answer 23

FALSE - it can, bc elimination is a first order process

Question 24

persistence factor depends ONLY on what 2 things

Answer 24

K and tau (rate constant of elimination and dosing interval)

Question 25

what does it mean when P=0.5 (persistence factor)

Answer 25

50% of the dose PERSISTS IN THE BODY

Question 26

persistence factor + _______ =1

Answer 26

loss factor

Question 27

"the fraction of each dose NOT persisting in the body"

Answer 27

loss factor

Question 28

true or false the loss factor only accounts for the portion of drug eliminated renally

Answer 28

FALSE - the mechanism of the elimination doesn't matter

Question 29

true or false the amount of drug in the body never reaches zero

Answer 29

true - 1st order elimination. technically there's always a TINY BIT left

Question 30

a steady state occurs after how many doses

Answer 30

8-10

Question 31

after ____ half lives, there is essentially 0% drug left

Answer 31

after 7 half lives have been COMPLETED

Question 32

what does a loss factor of 0.75 mean

Answer 32

75% of dose eliminated (regardless of what mechanism)

Question 33

after ____ half lives, a steady state is reached

Answer 33

7

Question 34

symbol for accumulation factor

Answer 34

S

Question 35

explain what an S (accumulation factor) of 1.75 means

Answer 35

after x amount of doses, the amount accumulated in the body is 175% of the original dose

Question 36

steady state/plateau is reached when the values of ________ are CONSTANT for each successive dose this can only happen when.....

Answer 36

cmax and cmin when there is no term containing "n" n is so large that -nkt approaches zero equilibrium is reached! amount eliminated = amount administerd

Question 37

during multiple dosing - when equal doses are given at fixed dosing intervals, the difference between cmax ss and c min ss is always....

Answer 37

Co!

Question 38

Co=....

Answer 38

dose/Vd

Question 39

which route is more popular to use multi dosing - IV or EV?

Answer 39

EV

Question 40

true or false the peak concentration in EV and IV administration is typically the same

Answer 40

FALSE - EV peak is typically lower bc the entire dose isn't placed into the blood all at once

Question 41

in extravascular administration, drug appears in the plasma due to....

Answer 41

absorption

Question 42

the extent of the "peak" (cmax) in extravascular administration depends on what?

Answer 42

the rates of absorption, distribution, and elimination also steady state concentration depends on the rates of these 3 things

Question 43

true or false unlike IV, during EV multiple dosing, earlier drug doses do NOT affect the pharmacokinetics of subsequent doses

Answer 43

true

Question 44

true or false in EV multi dosing, it is assumed that the entire drug dose is not completely absorbed

Answer 44

false - assumed that it is completely absorbed

Question 45

the main difference between drug accumulation of IV vs EV is.....

Answer 45

ABSORPTION of the drug if the EV drug is absorbed rapidly and completely, the plasma profiles will be very similar to IV except for the absorptive phase the terminal (elimination) portions of the 2 would be very similar

Question 46

the determination of plateau levels during multi-dosing of extravascular administration is similar to determining plateau levels in IV except for WHAT FACTOR

Answer 46

Ka has to be considered (absorption rate constant)

Question 47

for EV, when CAN you read tmax from the graph?

Answer 47

if the Ka is at least 5 times greater than K, the plasma profile will have a sharp peak -- can easily read tmax from the graph if not, need to use the formula for tmax (provided)

Question 48

for IV, cmax is the time that we do what? for IV, cmin is the time that we do what

Answer 48

cmax is the time that we give the next dose cmin is the time that we need to give the next dose

Question 49

what does it mean that the S value for aminophylline is 0.8

Answer 49

80% of aminophylline is theophylline. the other 20% is the ethylenediamine salt

Question 50

explain the 9:1:5:9 dosing regimen

Answer 50

each pattern is 24 hours - 12 hours on and 12 hours off patient doesn't have to wake up for a dose. the cmin is right before the 9am dose and the cmax is right after the 9pm dose

Question 51

when are we able to use the 9:1:5:9 dosing regimen

Answer 51

if the cmax is less than 20 and the cmin is over 10