Flashcards in Pharmacokinetics Deck (43):

1

## is the protonated form of a weak acid ionized or non-ionized?

### non-ionized

2

## is the protonated form of a weak base ionized or non-ionized?

### ionized

3

## do ionized or non-ionized forms of molecules cross membranes more easily?

### non-ionized

4

## definition: pKa

### pH at which 50% of drug is ionized and 50% is non-ionized

5

## if the pH is less than the pKa of a drug, which form predominates?

### protonated

6

## if the pH is greater than the pKa of a drug, which form predominates?

### unprotonated

7

## are weak acids protonated or unprotonated in the low pH environment of the stomach?

### protonated (non-ionized)

8

## are weak bases protonated or unprotonated in the high pH environment of the intestines?

### unprotonated (non-ionized)

9

## what factors affect drug distribution?

###
1. cardiovascular

2. tissue binding

3. molecule size

4. lipid solubility

10

## definition: phase I biotransformation

###
1. generates more polar molecule by exposing functional group on parent compound

2. readies compound for phase II

11

## definition: phase II biotransformation

### yields a more water soluble conjugated product to be excreted

12

## what types of reactions occur under phase I biotransformation?

### oxidative, reductive, hydrolytic

13

## what types of reactions occur under phase II biotransformation?

###
1. glucoronidation, sulfation, acetylation

2. glutathione conjugation, glycine conjugation, methylation, water conjugation

14

## definition: first pass effect

###
1. drug absorbed by the stomach or intestine will initially be carried to the liver by the portal vein

2. orally administered drug will be exposed to metabolizing enzymes by the liver

3. drug can be inactivated prior to reaching the intended target

15

## what is the mechanism of drug elimination?

### kidney

16

## drug elimination in the kidney depends on what factors?

###
1. GFR

2. binding to plasma proteins

3. alkalinization or acidification of urine

17

## what are the two key parameters that impact drug dosage?

###
1. volume of distribution

2. clearance

18

## definition: volume of distribution

### measure of the space in the body available to contain the drug (theoretical volume)

19

## definition: clearance

###
1. rate of elimination in relation to drug concentration

2. expressed as mL/mg/kg

3. helps determine capacity for drug removal by organs

20

## equation: volume of distribution

### V = amount of drug in body / concentration of drug in blood or plasma

21

## regarding volume of distribution, how does a very large V impact drug distribution?

### majority of the drug distributes to the extravascular compartment

22

## regarding volume of distribution, how does a V that is smaller or closer to the actual blood or plasma volume impact drug distribution?

### drug is retained primarily in the vasculature

23

## equation: clearance

### CL = rate of elimination / concentration of drug in blood or plasma

24

## definition: zero order elimination

###
1. specific amount of drug is eliminated over a period of time

2. elimination process is at capacity or saturated

3. independent of drug concentration

it doesn't matter how much drug you give, you will only get rid of a certain amount because there are only so many enzymes - reduction is by a constant amount

25

## what does zero order elimination look like on a time vs plasma concentration graph?

###
standard scale - negative linear

log scale - negative shoulder

26

## definition: first order elimination

###
1. not saturable

2. clearance is constant over the range of drug concentrations in the body

can handle all the drug being delivered, and then some - will always eliminate a constant fraction of drug

27

## what does first order elimination look like on a time vs plasma concentration graph?

###
standard scale - negative exponential (like half life)

log scale - negative linear

28

## definition: capacity-limited elimination

###
point at which the concentration of the drug has saturated the elimination capacities of the system - mimics zero order kinetics

doesn't matter if you've had 1 beer or 10 in an hour, you'll always eliminate 1 beer per hour

29

## definition: flow-dependent elimination

###
organ has high capacity or is NOT saturated by drug concentration - mimics first order kinetics

the greater the blood flow, the greater elimination

30

## which drugs are eliminated in a capacity-limited fashion?

### phenytoin, aspirin, alcohol

31

## which drug is eliminated in a flow-dependent fashion?

### propanolol

32

## half life is dependent on what factors, if being eliminated by first order kinetics?

###
1. volume of distribution

2. clearance

33

## how can initial plasma concentration be determined in a one compartment system?

###
extrapolating the semi-log plot of plasma concentration vs time - requires low volume of distribution (one compartment system) and first order elimination

Cpo = dose / volume of distribution

34

## what predicts the ratio of steady state concentration to dose seen following first dose?

### accumulation factor

35

## definition: accumulation factor

### AF = 1 / fraction lost in one dosing interval

36

## definition: bioavailability

### the amount of drug that reaches the systemic circulation

37

## what pharmacokinetic factors impact bioavailability?

###
1. extraction ratio, clearance, hepatic blood flow

2. absorption, metabolism, distribution

38

## how is bioavailability modeled graphically?

### measure area under concentration of drug in blood vs time curve

39

## what factors impact the area under the bioavailability curve?

### rate and extent of absorption - dictate if drug will reach target concentration

40

## what factor affects the extent to which a drug will reach circulation?

### first pass metabolism / extraction ratio

41

## definition: steady state concentration

### point during dosing regimen when elimination of a drug is equal to bioavailability of drug - relationship between half life and steady state

42

## the time a drug takes to reach steady state concentration is dependent only on which factor?

### half life

43