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Flashcards in Pharmacokinetics Deck (74):
1

what is pharmacokinetics

the study of the time course of drug concentration in the body, usually as reflected in the plasma concentration (fate of drug in the body).

2

first order kinetics is also referred to as what

exponential kinetics characterized by a constant fractional change per unit time

3

first order kinetics is measured as what

the rate constant (Ke)

4

zero order kinetics is also referred to as what

saturation kinetics

5

first order kinetics is characterized by what

a constant amount of change per unit time

6

half-time or biological half life (t 1/2)

for drugs that are eliminated by first-order kinetics, the fractional change in the amount of drug in the blood is generally expressed by the half-life. Time required for 50% of the drug remaining in the body to be eliminated (or the time required for the blood concentration to decrease 50%).

7

rate constant of elimination (Ke)

For drugs that are eliminated by first-order kinetics, the rate constant is the fractional change per unit time (fraction/min, fraction/hour, etc)

8

rate constant of elimination (Ke) is equal to what

0.693 / t1/2
OR
t1/2 = 0.693/ke

9

what is clearance

the quantification of elimination

10

for most drugs in clinical setting, clearance is

constant

11

clearance represents the volume of

biological fluid that would have to be completely freed of drug to account for the rate of elimination (ie. the volume of body fluid processed in a given time)

12

clearance is expressed as

volume per unit time

13

individual organ clearances are

additive
ie. take renal cl, pulmonary cl etc. and add the volumes up to give you total systemic clearance

14

clearance can be calculated from what

1. excretion rate/concentration
2. dose/area under the curve (AUC)

15

compartmental model of pharmacokinetics

uses selected model to "fit" parameters to data

16

noncompartmental model of pharmacokinetics

most use the same basic principles (Trapezoidal rule; observed data; calculated elimination rate constant; standard formulas for the rest)

17

Fate of a drug

1. liberation
2. absorption
3. distribution
4. metabolism
5. excretion

18

what is liberation

release from matrix

19

what is absorption

process and rate

20

what is distribution

movement in body

21

what is metabolism

removal by biotransformation

22

what is excretion

physical removal from body

23

what are key pharmacokinetic parameters

-clearance
-volume of distribution
-half-life
-bioavailability

24

what is volume of distribution

concept for a given dose, the theoretical size necessary to produce a specific calculated exposure

25

what is half-life

the length of time necessary to reduce or "eliminate" 50% of the current level of drug

26

what is bioavailability

the fraction of the dose that reaches systemic circulation

f=1 for IV

27

assumptions of a one compartment model

-the body is a single compartment with a volume (V) and drug concentration (C)
-distribution of drug is uniform and rapid compared with absorption and elimination
-elimination of the drug conforms to 1st order kinetics

28

see diagram: slide 10-11

see diagram: slide 10-11

29

assumptions of a two compartment model

-the body contains 2 compartments, central and peripheral
-all kinetics are first order
-elimination is form the central compartment

30

see diagram: slide 12 + 13

see diagram: slide 12 + 13

31

what are model independent parameters

-clearance, half-life, Vd
-AUC
-Cmax (max concentration)
-Tmax (time of max concentration)

32

see calculations: slide 16

see calculations: slide 16

33

what is the plateau principle

-when a drug is administered intravenously, the plasma concentration will increase until the rate of elimination and administration are equal
-at that point, the plasma drug [ ] will remain constant until there is a change in the dosage rate of elimination kinetics

34

steady state concentration (Css) equation

rate of administration/total body Cl = dosing rate/Cl

35

dosing rate equals

Cl x Css

36

Css equals

dosing rate/Cl

37

see diagram: slide 19

see diagram: slide 19

38

time required to achieve steady state depends on

half life

39

how many half lives does it take to achieve steady state

4-6 half-lives

40

see diagram: slide 21

see diagram: slide 21

41

conditions for fixed rate, multiple doses

-the drug will accumulate in the body if the time interval between doses is less than 4 half lives
-total body stores of the drug increase exponentially to a plateau
-the plasma [ ] will fluctuate during the dosing interval
-Css now represents the mean [ ] of the drug during the dosing interval

42

for oral dosing, what will also influence Css

bioavailability

43

what is bioavailability

is the fraction (f) of the administered dose that reaches the systemic circulation

44

what is the equation of Css in a fixed rate, multiple dose regimen

Css = (f) x dose / (dosing interval x Cl)

45

what happens to the [plasma] with a fixed rate multiple dose regimen

[plasma] will fluctuate btwn a maximum (peak) and a minimum (trough) concentration

46

see diagram: slide 24

see diagram: slide 24

47

for therapy characterized by repeated intermittent dosing, the choice of dosage interval is based on what

-tolerance btwn dose variations of serum concentraions (based on half life and toxicity of the drug)
-patient convenience plays a role for out patient therapy

48

when would a loading dose be administered

when the time to reach steady state is needed immediately

49

the amount of drug required to achieve a given steady-state value in plasma is the amount that

must be in the body when the desired steady-state is reached

50

what variable relates the total drug [ ] in the body to the plasma [ ]

Vd

51

loading dose equation is

loading dose = Css x Vd

52

what is nonlinear, dose-dependent or saturable elimination kinetics

a capacity-limited process where drugs exceed the metabolic/excretory capacity of the body to eliminate that drug as a linear rate

53

describe the clearance rate of a nonlinear elimination

Cl will vary with the [ ] of drug in a manner analogous to the M-M equation for enzyme kinetics

54

virtually all drugs taken by pregnant women are transferred to some degree across the

placenta to the fetus

55

delivery of single doses in pregnant women is limited by what

blood flow to the placenta

56

when does peak fetal blood concentration occur

btwn 20 mins and 4 hrs after IV dosing depending on the chemical characteristics of the drug

57

chronic dosing during pregnancy can lead to what

a steady-state
fetal:maternal [ ] approach unity

58

what are 5 critical time frames of pediatric pharmacology

1. conception to birth
2. birth to 1 month
3. 1 month to 2 yrs
4. 2 years to 12 yrs
5. 12 yrs to 18 yrs

59

what drug characteristics affect developmental factors

-drug absorption
-drug distribution/% body water
- drug metabolism
-drug excretion

60

dosages are determined by

-formula
-body to surface area

61

drug disposition and aging is determined by what

-absorption
-distribution
-drug metabolism

62

how is absorption affect by age

relatively normal

63

how is distribution affect by age

aging is characterized by decreased lean body mass, increased % of body weight represented as fat, and decreased total body water

64

how is drug metabolism affected by age

-slower on average in the elderly due to decreased hepatic blood flow and smaller liver size

65

does the aging liver decreases its metabolism for all drugs

the aging liver to metabolize drugs does not decline in a similar way for all pharmacological agents, and the clearance of some drugs is largely unchanged (depends on intrinsic Cl)

66

what is the cockroft-gault equation

-estimates the glomerular filtration rate and generally
-obtained by estimating endogenous creatine clearance

67

what is cockroft-gault equation

CreatineCl = [140-age] [weight] / (72 x serumcr in mg/dL)

68

for women, creatinine clearance is --% of the value calculated by the Cockroft-Gault eqn

85%

69

why might the GRF be overestimated using the Cockroft-Gault eqn in older individuals with low [ ]

bc endogenous creatinine production from muscle is decreasing with age

70

how does age affect renal excretion

-aging is associated with decreased renal size and renal blood flow, leading to decreases in glomerular filtration rate

71

decreases in tubular function parallel those in

glomerular function

72

based on cross-sectional studies, creatinine clearance decreases an average of

8ml/min/decade after age 30

73

what dosage adjustments are done for renal dysfunction

1. decrease dose, but maintain dosage interval
2. maintain dose, but increase length of dosage intervals

74

when is decreasing dose the preferred method of dosage adjustment for renal dysfunction

when a relatively constant plasma concentration of the drug is desired