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Flashcards in 1: Clinical Pharmacokinetics 2 Deck (27):
1

what are the three components of renal clearance?

CLrenal = filtration + secretion - reabsorption

2

what is a normal GFR?

120 mL/min

3

what types of drugs are filtered by the glomerulus?

only unbound drugs

4

what are two markers for GFR?

creatinine and inulin
-unbound to plasma proteins
-neither secreted nor absorbed
-about 100 mL/min

5

renal clearance and dosage adjustment + corrected dose equation

renal disease often changes drug clearance -> this can be used to adjust dose to maintain the Css

corrected dose= avg dose (pt CLcreatinine/ 100 ml/min)

6

when do you adjust dosages?

only when drug is >50% cleared by renal elimination and renal fxn is reduced to 50% or less of normal

7

first order elimination

-constant % of drug eliminated/time
-when drug dose increases, Css increases proportionately
-how 95% of drugs work
-accumulation + elimination change exponentially for a single dose over time
-linear Cp accumulation with increase in dose

8

zero order elimination

-constant amount of drug eliminated/time
-ER same regardless of [C]
-linear decrease in [C] over time
-non-linear Cp accumulation with increase in dose

9

Michaelis-Menton kinetics: rate of elimination

= (Vmax x C)/(Km + C)

10

definition of Km

[drug] at 50% of Vmax
-measure of the affinity of the substrate for the enzyme

11

definition of half life

time it takes to eliminate 50% of the drug from the body - only applies to first order drugs

12

what is the elimination rate constant?

K or Ke - fraction of Vd elimination remains constant per unit time

13

equation for half life

= 0.693/ Ke = (0.693 x Vd)/ CL

14

is half life dependent on concentration?

newp

15

describe the accumulation and elimination of a drug according to half-lives

95% of final accumulation plateau reached after 4.5x
95% of total dose eliminated after 4.5x

16

why is half life important? (3 reasons)

1. determine time to reach Css
2. determine duration of action
3. determine proper dosing frequency to avoid large fluctuations in Cp

17

how will doubling the dose administered change the duration of action?

increases duration by one half life

18

one compartment model: Vd with elimination
-equation for Vd
-assumptions

Vd = dose/Co

Assumptions:
-FIRST ORDER
-body is ONE homogeneous compartment
-instantaneous mixing

19

two compartments: Vd distribution without elimination

-distribution b/w compartments slower than distribution within each compartment
-distribution phase typically

20

two compartments: Vd distribution with elimination

-distribution to 2nd compartment slower than distribution w/i 1st compartment

21

two compartment model assumptions

-FIRST ORDER
-instant mix in 'each' compartment
-slower mix 'between' compartments

22

designing dose regimens for i.v. vs p.o: DR

iv: DR = (CL)(Css)

po: DR = (CL x Css)/F

23

designing dose regimens for i.v. vs p.o: loading dose

iv: loading dose = (Vd)(target Cp)

po: loading dose = (Vd x target Cp)/F

24

designing dose regimens: therapeutic window at different values of half life

-if dosing interval = t1/2, Cmax/Ctrough = 2
-if dosing interval t1/2, Cmax/Ctrough > 2 (may exceed therapeutic window)

25

equation to adjust dosage regimen

new rate = (old rate)(desired Css/ measured Css)

26

what is the purpose of therapeutic drug monitoring?

use Cp to:
-individualize dose
-predict effect
-diagnose toxicoses

27

what kinds of drugs are monitored?

-marked PK variability
-narrow therapeutic window
-therapeutic and AE related to [drug]
-desired therapeutic effect difficult to monitor
-inter-individual variation in PK parameters