Pharmacokinetics

Question 1

what is Cmax? what is it determined by?

Answer 1

highest concentration achieved by the drug in plasma. deterred by amount and bioavailability of drug administered and relative rates fo absorption, distribution to tissues, and metabolism/elimination

Question 2

what is Tmax

Answer 2

time at which the drug reaches its highest measured concentration in the plasma

Question 3

what does the area under the concentration curve (AUC) measure

Answer 3

animals total exposure to drug

Question 4

what is half life

Answer 4

length of time it takes for the concentration of drug in plasma to decrease by half

Question 5

when dose is doubled, what happens to the duration of drug action

Answer 5

extended by one half-life

Question 6

what is dose (mg/kg) determined by

Answer 6

minimum effective concentration and toxic concentration

Question 7

what is dose interval (times per day) determined by

Answer 7

clearance and half life

Question 8

if dosage interval is greater than 5 half lives, at what rate will the drug accumulate in the body

Answer 8

no drug will accumulate in the body

Question 9

what is dose rate (dose of drug per unit time) determined by

Answer 9

dose and dose interval

Question 10

when we reach steady state, what is the relationship between rate of elimination and dosing rate

Answer 10

rate of elimination = dosing rate (drug concentration is no longer changing)

Question 11

you want to reach therapeutic concentration quickly but there is a long half life. how can you shorten the time until a clinical effect is seen

Answer 11

give a loading dose (equal to volume of distribution x desired drug concentration)

Question 12

what is drug absorption

Answer 12

refers to movement of drug from its site of administration to the blood

Question 13

when is absorption not considered to factor into the pharmacokinetics

Answer 13

when a drug is given IV

Question 14

why are lipophilic drugs more readily absorbed

Answer 14

pass through hydrophobic lipid membrane more easily

Question 15

what is a common generally safe route of administration for a drug that is affected by GI transit times? what are 3 factors influencing absorption of this route of administration?

Answer 15

oral; variable absorption between individuals, species, and fed/fasted status

Question 16

what is bioavailability

Answer 16

percentage of a drug dose that reaches systemic circulation

Question 17

what does it mean if there is a large difference between the oral and IV dose of a drug

Answer 17

poor bioavailability is likely

Question 18

why are unionized drugs better at crossing lipid membranes than ionized drugs

Answer 18

more lipid soluble (like non-ionized in like)

Question 19

what does relationship between pH of the environment and pKa of a drug determine

Answer 19

whether the drug is ionized or non-ionized in its environment, and therefore affects its absorption

Question 20

what drug route of administration has a bioavailability of 100%

Answer 20

IV (intravenous)

Question 21

name at least 3 factors that influence the speed of distribution

Answer 21

blood flow/organ perfusion; ability of the drug to bind to the specific tissue and to plasma proteins; extent of distribution; rate of dissuasion across membranes; active transport of the drug across membranes

Question 22

what is Vd?

Answer 22

apparent volume of distribution: the theoretical volume that would be needed to maintain the total amount of administered drug at the initial concentration (C0) in plasma after IV administration (Or at Cmax after other forms of administration); represents degree of tissue distribution of drug

Question 23

how is Vd calculated?

Answer 23

Vd (mL or L/kg) = dose (mg/kg) / C0 (mg/mL or mg/L)

Question 24

what does a HIGH Vd value mean?

Answer 24

MORE distribution from the blood into the tissues, so significant intracellular penetration. a high Vd value DOES NOT indicate penetration into a specific site, only general tissue distribution.

Question 25

what does a LOW Vd mean?

Answer 25

LESS distribution from blood into the tissues, so predominantly in ECF

Question 26

ion trapping affects the apparent volume of distribution. what will each unit of pKa away from pH in a compartment result in?

Answer 26

a 10x change in concentration of the drug in that compartment

Question 27

will a basic drug accumulate or be absorbed from an acidic environment

Answer 27

accumulate (this is a consequence of ion trapping)

Question 28

will an acidic drug accumulate or be absorbed from an acidic environment

Answer 28

be absorbed. (this is a consequence of ion trapping)

Question 29

Snickerdoodle has an infection. Her milk has a pH of 6.8 and her blood plasma has a pH of 7.4. You give her benzylpenicillin which has a pH of 2.7. Will the concentration of benzylpenicillin be greater in the milk or plasma?

Answer 29

plasma. (benzylpenicillin pKa < milk and plasma pH, so ionized form of benzylpenicillin will predominate in both milk and plasma. the plasma pH is further from the pKa of the drug, so the drug will be more ionized in the plasma, and more of the ionized drug will be in the plasma. the non-ionized drug will equilibrate between tissues, meaning that the total drug will be higher in the plasma.)

Question 30

what is metabolism

Answer 30

biotransformation of drugs to facilitate elimination

Question 31

how is metabolism generally achieved

Answer 31

by reactions that increase the polarity/water solubility of the drug

Question 32

what is the main site of drug metabolism

Answer 32

liver

Question 33

what are 3 important factors that influence metabolism

Answer 33

age (metabolic enzymes may not be fully functional in neonates), health (especially liver disease can reduce ability to metabolize drugs), species (species differences in ability to metabolize drugs; can’t extrapolate safe or effective doses between species)

Question 34

main enzymes responsible for phase 1 drug metabolism

Answer 34

cytochrome P450 enzymes

Question 35

briefly, what does phase 2 metabolism involve?

Answer 35

increase water solubility by conjugating drug to exogenous substrates (glucoronidation, sulphate conjugation, acetylation) and deactivate active metabolites

Question 36

what are 3 types of conjugation in phase 2 metabolism

Answer 36

glucuronidation (transfer glucuronic acid to substrate), sulphate conjugation (transfer of sulphate to substrate), acetylation (transfer acetyl group to substrate). also glutathione conjugation and methylation, but these are less important

Question 37

after phase 2 metabolism, large drug molecules are typically excreted in ______, while small drug molecules are typically excreted in ______

Answer 37

bile; urine

Question 38

what is the most important organ of drug elimination

Answer 38

kidney (exception: large drug molecules are more likely to be eliminated via secretion from liver into bile)

Question 39

what is distribution largely determined by? what system is most important for distribution?

Answer 39

blood flow; cardiovascular system

Question 40

what is primary site of absorption of orally administered drugs

Answer 40

small intestine

Question 41

what processes determine the rate of renal excretion?

Answer 41

filtration + secretion - reabsorption. (therefore drugs or diseases that affect renal function will alter the renal elimination of drugs)

Question 42

what is total body clearance affected by

Answer 42

total body clearance = hepatic clearance + renal clearance + other clearance