lecture 2

Question 1

What are the 4 major processes involved in drug pharmokinetics, and what are their “sites”

Answer 1

1. absoprtion- small intestine
2. distribution- cardiovascular system
3. metabolism - liver
4. elimination- kidney

Question 2

when comparing a concentration- time profile between an orally and IV administered drug, what will be the difference

Answer 2

IV drug will not have an absorption phase

Question 3

what is Cmax

Answer 3

the highest concentration achieved by the drug in the plasma

Question 4

what is Tmax

Answer 4

time it takes for the drug to reach highest measured concentration

Question 5

duration of drug action is _________ when the dose is doubled

Answer 5

extended by 1 half life

Question 6

what does the dose interval need to be in order for the drug to be completely cleared between each dose

Answer 6

greater than 5 half lives

Question 7

define steady state

Answer 7

drug concentration is no longer changing, the rate of elimination = dosing rate

Question 8

what is dosing rate versus dosing interval?

Answer 8

dosing rate is the dose of drug per unit time, dosing interval is just time interval

Question 9

total body clearance=

Answer 9

hepatic clearance + renal+ other clearance

Question 10

what is the point of a loading dose

Answer 10

to reach therapeutic levels quicker with drugs that have longer half lives

Question 11

in general withdrawal times approximate how many half lives for 99.9% clearance. what about 95% clearance of the drug

Answer 11

10, 5

Question 12

which class of drugs are more readily absorbed? why?

Answer 12

lipophilic drugs- the ADME of PK require all drugs to go through cell membranes- the lipid bilayer

Question 13

why would SQ and IM have a lower Cmax than IV given at the same dose?

Answer 13

due to absorption time- ADME processes are happening all at once so even though full dose isn’t absorb D+M+E are already underway

Question 14

a large difference between oral and IV dose suggest

Answer 14

the drug has poor bioavailability (the % of dose that reaches systemic circulation)

Question 15

describe the first pass effect

Answer 15

the loss of drug due to metabolism in the GI and or liver before it enters systemic circulation

Question 16

what is one way to by pass the first pass effect

Answer 16

rectal administration- 50% of circulation from rectal area bypasses the liver

Question 17

why is absorption of acidic drugs better in an acidic environment, and the same concerning basic drugs

Answer 17

acids are ionized in basic environments, ionized molecules have a harder time passing through lipid bilayer

Question 18

higher volume of distribution means

Answer 18

more drug in tissues from blood

Question 19

what does vd tell you

Answer 19

predicts cmax after a single dose (dose/vd) - a low vd means that drug is mostly in ECF, high means its going to the cells

Question 20

each unit of pKa away from pH results in a _________ in the concentration of the drug in that compartment

Answer 20

10 fold change

Question 21

what is ion trapping

Answer 21

since molecules are in the ionized form when their pKa is far away from the environmental pH, they can get stuck in areas that put them in their ionized state. the rumen is a prime location for this and can lead to drugs getting degraded before they enter the circ.

Question 22

why can only free non bound drugs distribute into tissues

Answer 22

they are too large to pass through the membrane

Question 23

drugs that are protein bound may be desirable because

Answer 23

they have longer acting time since there is a slow release as they become unbound from the proteins

Question 24

metabolism of drugs usually leads them being

Answer 24

more polar/ able to dissolve in water

Question 25

what are the two phases of drug metabolism

Answer 25

phase 1 : redox
phase2: enzymatic

Question 26

what is important to consider concerning drug metabolism

Answer 26

age, species and health

Question 27

what is cytochrome p450?

Answer 27

the main enzyme involved in phase one metabolism, it catalyzes oxidation reaction RH+O2+NADPH+H–> R-OH +H2O+ NADP+

Question 28

phase 2 of drug metabolism leads to

Answer 28

increasing water solubility by conjugating the drug to exogenous substrates and deactivates active metabolites

Question 29

what are the 3 most important types of conjugation reactions involved in drug metabolism

Answer 29

1. glucuronidation
2. sulfate conjugation
3. acetylation

Question 30

what is p-glycoprotein, what does it do?

Answer 30

the most important of transport proteins- and efflux transporter- moves substrates out of the cells

Question 31

where are large drug molecules typically excreted? small?

Answer 31

bile, urine

Question 32

rate of renal excretion = ?

Answer 32

filtration + secretion - reabsorption

Question 33

what is enterohepatic recirculation?

Answer 33

molecules eliminated in the bile get reabsorbed when they go back into the SI

Question 34

what drug reaction typically under goes enterohepatic recirculation

Answer 34

glucuronidation