Flashcards in 1: Clinical Pharmacokinetics 2 Deck (27)

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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