Pharmacokinetics

Question 1

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

Answer 1

non-ionized

Question 2

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

Answer 2

ionized

Question 3

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

Answer 3

non-ionized

Question 4

definition: pKa

Answer 4

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

Question 5

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

Answer 5

protonated

Question 6

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

Answer 6

unprotonated

Question 7

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

Answer 7

protonated (non-ionized)

Question 8

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

Answer 8

unprotonated (non-ionized)

Question 9

what factors affect drug distribution?

Answer 9

1. cardiovascular
2. tissue binding
3. molecule size
4. lipid solubility

Question 10

definition: phase I biotransformation

Answer 10

1. generates more polar molecule by exposing functional group on parent compound
2. readies compound for phase II

Question 11

definition: phase II biotransformation

Answer 11

yields a more water soluble conjugated product to be excreted

Question 12

what types of reactions occur under phase I biotransformation?

Answer 12

oxidative, reductive, hydrolytic

Question 13

what types of reactions occur under phase II biotransformation?

Answer 13

1. glucoronidation, sulfation, acetylation

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

Question 14

definition: first pass effect

Answer 14

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

Question 15

what is the mechanism of drug elimination?

Answer 15

kidney

Question 16

drug elimination in the kidney depends on what factors?

Answer 16

1. GFR
2. binding to plasma proteins
3. alkalinization or acidification of urine

Question 17

what are the two key parameters that impact drug dosage?

Answer 17

1. volume of distribution

2. clearance

Question 18

definition: volume of distribution

Answer 18

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

Question 19

definition: clearance

Answer 19

1. rate of elimination in relation to drug concentration
2. expressed as mL/mg/kg
3. helps determine capacity for drug removal by organs

Question 20

equation: volume of distribution

Answer 20

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

Question 21

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

Answer 21

majority of the drug distributes to the extravascular compartment

Question 22

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

Answer 22

drug is retained primarily in the vasculature

Question 23

equation: clearance

Answer 23

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

Question 24

definition: zero order elimination

Answer 24

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

Question 25

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

Answer 25

standard scale - negative linear | log scale - negative shoulder

Question 26

definition: first order elimination

Answer 26

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

Question 27

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

Answer 27

standard scale - negative exponential (like half life) | log scale - negative linear

Question 28

definition: capacity-limited elimination

Answer 28

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

Question 29

definition: flow-dependent elimination

Answer 29

organ has high capacity or is NOT saturated by drug concentration - mimics first order kinetics the greater the blood flow, the greater elimination

Question 30

which drugs are eliminated in a capacity-limited fashion?

Answer 30

phenytoin, aspirin, alcohol

Question 31

which drug is eliminated in a flow-dependent fashion?

Answer 31

propanolol

Question 32

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

Answer 32

1. volume of distribution | 2. clearance

Question 33

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

Answer 33

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

Question 34

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

Answer 34

accumulation factor

Question 35

definition: accumulation factor

Answer 35

AF = 1 / fraction lost in one dosing interval

Question 36

definition: bioavailability

Answer 36

the amount of drug that reaches the systemic circulation

Question 37

what pharmacokinetic factors impact bioavailability?

Answer 37

1. extraction ratio, clearance, hepatic blood flow | 2. absorption, metabolism, distribution

Question 38

how is bioavailability modeled graphically?

Answer 38

measure area under concentration of drug in blood vs time curve

Question 39

what factors impact the area under the bioavailability curve?

Answer 39

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

Question 40

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

Answer 40

first pass metabolism / extraction ratio

Question 41

definition: steady state concentration

Answer 41

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

Question 42

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

Answer 42

half life

Question 43

what is required in order to administer a maintenance dose?

Answer 43

dosing rate (clearance x target concentration) maintenance dose = dosing rate x dosing interval