Flashcards in Pharm: Pharmacokinetics I Deck (41):

1

## What is drug clearance (abbrev. CL)?

### the theoretical volume of fluid from which a drug is removed per unit time

2

## What are the fundamental differences between therapeutic implications of zero-order and first-order elimination kinetics?

###
Zero-order kinetics drugs are metabolized by enzymes, which are saturable RLS, and are metabolized at a constant amount per unit time, thus no plateau observed.

First-order kinetics drugs are metabolized at a constant fraction per unit time (half-life) and will show a plateau.

3

## What is the concept of apparent volume distribution?

### the apparent space the drug resides in

4

## What is the concept of elimination half-life? What is its relationship to clearance and volume of distribution?

### the rate of drug removal

5

## How is elimination half-life calculated mathematically?

###
Ke = CL / Vd

*Ke is the elimination constant

*units is 1/min

**The change in drug concentration with respect to time is equal to the slope of concentration vs. time plot, or -Ke, or natural log of C/Co = -Ke x t

T1/2= 0.7/Ke

6

## What is the plateau principle, and how is it applied to drug sampling intervals and expected time course of drug in the body?

### the plateau principle says that the time to steady state is dependent on the half-life; fluctuations will be proportional to the dose interval over the half-life: increasing dose interval will lead to greater fluctuations; decreasing it will lead to increased steady-state concentrations and smaller fluctuations

7

## What are the main reasons to study pharmacokinetics?

###
1. there is a relationship between concentration of drug (bioavailable) and its effects

2. to develop a rational framework for dosing

3. improve therapeutic efficacy by selecting dosing regimens to match patients' parameters

8

## If a clinician typically wants to maintain steady-state concentrations of a drug within the therapeutic window, how should the drug be administered?

### At the same rate it's eliminated

9

## What is the formula for mathematically calculating dosing rate?

###
dosing rate = CL x Css

*CL = clearance rate

*Css = [desired] steady-state concentration

10

## What is the formula for mathematically calculating clearance?

### rate of elimination / concentration

11

## What is the formula for mathematically calculating systemic clearance?

### CL =CLrenal + CLhepatic + CLother

12

## What is the formula for mathematically calculating rate of drug elimination of an organ?

###
= Q x Ca - Q x Cv

=Q(Ca-Cv)

*Q = blood flow to the organ

*Ca = arterial drug concentration

*Cv = venous drug concentration

13

## What is the formula for mathematically calculating clearance for an organ?

###
CLorgan = Q[(Ca-Cv) / Ca] = Q x E

*E = extraction ratio

14

## For drugs handled by the kidney, ____ clearance is most important to watch.

### renal

15

## What is the limiting variable in drug clearance?

### blood flow (presentation of drug) to the organ

16

## What is the extraction ratio (E)?

### the fraction of drug that has been presented on the arterial side that is removed by the organ

17

## On a linear graph of drug concentration over time, how will first- and zero-order kinetic reactions appear?

###
first order = exponential decay

zero order = linear

18

## On a graph of log drug concentration over linear time, how will first-order kinetic reactions appear? What does this mean?

### first order = linear; this means that a constant fraction of the drug will be eliminated per unit time (ex: half-life)

19

## Remind me: what is the volume of distribution?

### the volume of fluid that would be required to contain all of the drug dose at the same concentration as exists in the blood or plasma; Vd = amount of drug in body / blood concentration

20

## What is significant about the time at which C0/C = 2?

### This is the time of the half-life-- this formula indicates that the original drug concentration (C0) divided by the current concentration (C) equals 2

21

## In the body, a drug's half life is the time it takes for the concentration of drug in ____ to be reduced by 50%.

### plasma

22

## What is clinical significant about half-life determination?

###
-to determine the dosing interval

-to help determine dose

-may determine route of administration

-indicates time required to reach steady-state

23

## True or false: a drug is usually given at half-life intervals to maintain steady state dosing.

### True

24

## What route of administration might be the best for drugs with short half-lives?

### intravenous

25

## What is a pharmacokinetic model?

### model used for designing and rationalizing pharmaco-therapy regimens; single-IV dose models are a simple, one-compartment open-system model

26

## Two compartment open model for pharmacokinetics assumes that much of a drug is in one particular compartment (often blood) and that an equilibrium exists between what? What happens during and after equilibration?

### that first particular compartment (often blood) and other areas; as it equilibrates the concentration drops rapidly, following equilibration the concentration follows a first-order model for elimination

27

## What model is most realistic for the body?

### multicompartment models (requires computer assistance); clearance equals the dose divided by the area under the curve (curve of concentration in blood over time)

28

## What is the bioavailability term, F, used for?

###
modifying the dosing rate equation to account for variable bioavailability which will affect the dosing rate needed to maintain steady state concentrations; added to formula as follows:

Dosing rate x F = CL x Css

29

## About how many half-lives does it take to achieve steady-state?

### about 4-5

30

## Time to steady state is independent of ____ or ____ ____, but strictly dependent on ____.

### independent of dose or dose interval; dependent on half-life

31

## What clinical features will be seen or not seen below the therapeutic range?

### no clinical benefit will be seen

32

## What clinical features will be seen or not seen above the therapeutic range?

### toxicity may be seen

33

## Clinicians can control what aspects of drug administration that will affect the peak/trough and magnitude of the Css?

### the dosing interval and the dose

34

## What formula is used to determine the infusion rate for IV administered drugs?

### CSS = infusion rate / total body clearance

35

## What is the definition of a loading dose?

### the desired steady state concentration of a drug times the volume of distribution adjusted for bioavailability;

36

## Why might loading doses be dangerous?

### due to the high concentrations that are achieved

37

## What is the practice of loading dosing for therapeutic use?

### administering enough drug to achieve desired Css when one cannot wait for 5 half-lives to achieve a therapeutic range; e.g. in heart attacks, serious heart failure, overwhelming bacterial infections, etc.

38

## What is the practice of maintenance dosing for therapeutic use?

###
following the loading dose, drug is given in maintenance doses to keep the drug within the therapeutic window such that:

Dosing rate = (target Css x CL) / F

39

## For zero order kinetics drug elimination, Km is used to modify LD, CSS, and DR equations. What is Km?

### Km is the dose that produces 50% of the maximal elimination rate

40

## For zero order kinetics drug elimination, Vm is used to modify LD, CSS, and DR equations. What is Vm?

### Vm is the maximum rate of the elimination process

41