Lecture 2: Pharmokinetics

Question 1

Drugs can be bound to______. This happens generally via _____

Answer 1

blood proteins

electrostatic attraction

Question 2

only ________ can distribute into tissues and interact with targets to have a pharmacodynamic effect

Answer 2

free, non bound drugs

Question 3

conditions that affect ______ can affect the levels of free drug in the body

Answer 3

plasma protein levels such as hypoalbuminemia with chronic renal failure

Question 4

the percent of drug that is ______ stays stable regardless of the concentration in the blood

Answer 4

protein bound

Question 5

protein binding of less than ____ is not clinicaly very relevant

Answer 5

80%

Question 6

what is the name of the drug that has a protein binding of more than 99% and slowly dissociates?

Answer 6

convenia (cefovecin)

Question 7

metabolism is acheived via reactions that increase the _______ of a drug

Answer 7

water solubility/polarity

Question 8

the main site of drug metabolism is the

Answer 8

liver

Question 9

drug metabolism has 2 phases which are

Answer 9

redox and enzymatic

Question 10

list some factors that can affect metabolism function and speed

Answer 10

age, health, and species

Question 11

what is the name of the enzymes located in the liver that are found in intracellular organelles that increase the water solubility of drugs via an oxidation reaction?

Answer 11

cytochrome P450

Question 12

upregulation of CYP enzyme familis results in ______

down regulation of CYP enzymes results in _____

Answer 12

loss of therapeutic effect because metabolism will increase

toxicity of the drug because it is not being metabolized enough

Question 13

phase 2 of metabolism involved increasing water solubility by ________

Answer 13

conjugating the drug to exogenous substrates

Question 14

what are the 3 most common conjugation reactions?

which species can do which ones?

Answer 14

glucuronidation (cats deficient)

sulfate conjugation (pigs not very good)

acetylation (dogs can’t)

Question 15

the most important drug transport protein is _____, also known as ______

Answer 15

P-glycoprotein

multidrug resistance protein 1

Question 16

P-glycoprotein is a _____ that moves substrates ____ of cells

Answer 16

effulx transporter

OUT

Question 17

all drugs are filtered by the _____, EXCEPT FOR ____

Answer 17

glomerulus

protein bound drugs

Question 18

some drugs can be eliminated without _____

Answer 18

prior metabolism

Question 19

rate of renal excretion =

Answer 19

filtration + secretion - reabsorption

Question 20

doses of drugs that are excreted by the kidney at least ___ unmetabolized should be reduced.

Answer 20

50%

Question 21

what kind of molecules are likely to be excreted by the bile?

Answer 21

large molecules

Question 22

what is enterohepatic recirculation?

what is the result?

Answer 22

when a drug is excreted into the small intestine with bile and it is then reabsorbed by the small intestine

result is prolonged drug exposure, double peaks on concentration vs time graphs

Question 23

What is Cmax?

Answer 23

highest concentration achieved by a drug in the plasma

Question 24

what is Tmax?

Answer 24

the time it takes to reach Cmax

Question 25

what is the AUC?

Answer 25

area under curve, total drug exposure

Question 26

what is the half life?

Answer 26

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

Question 27

doubling a dose of a drug extends by _____ the time it takes to reach a specific concentration

Answer 27

one half life

Question 28

if a dosing interval is more than 5 half lives, then…

Answer 28

no drug will accumulate in the body and it will be fully cleared with each dose

Question 29

the dose of the drug is decided by

Answer 29

the minimum effective concentration and the toxic concentration

Question 30

the dose interval is decided by

Answer 30

the half life and clearance of the drug

Question 31

what is steady state?

steady state is usually achieved after ____ half lives

Answer 31

when the amount of drug going into the body equals the amount leaving the body over the doing interval

5

Question 32

what is a loading dose and why would you use it?

Answer 32

giving a single larger dose at the beginning of therapy. you would use this when you want to reach higher concentrations wuickly but the half life of the drug is very long. it is used to shorten the time to clinical effects of the drug

Question 33

in general, withdral times are how many half lives?

Answer 33

10

Question 34

drugs that are more _____ and less _____ are more easily passed across cell membranes

Answer 34

lipophilic, polar

Question 35

what is bioavailability?

Answer 35

percentage of a drug that reaches the systemic circulation. IV drugs have a bioavailability of 100%

Question 36

what is the first pass effect?

Answer 36

loss of a drug occurring by metabolism/degredation in the intestinal wall and liver during absorption

Question 37

drugs with a high first pass effect have a _____ bioavailability

Answer 37

lower

Question 38

when the pKa is lower than the pH of the environment, the _____ will predominate. Meaning what?

Answer 38

protonated

acids will be non ionized

bases will be ionized

Question 39

when the pKa is higher than the pH of the environment, the ____ form will predominate. Which means what?

Answer 39

deprotonated

acids will be ionized

bases will be non ionized

Question 40

Absorption of drugs that are acids will be better in an ____ environment, and drugs that are bases will be absorbed better in a _____ environment

Answer 40

acidic, like stomach

basic, like small intestine

Question 41

meloxicam is an acid, pKa of 4.1. Will it be more absorbed in the atomach or the SI?

Answer 41

the stomach since it is more acidic

Question 42

if you give a drug with a pKa of 8.8, will it be more or less ionized in the stomach?

Answer 42

stomach has a pH of 2, so this means the deprotonated form will predominate, meaning the acid will be more ionized in the stomach. it will therefore be better absorbed in the SI where it is more basic and nonionized

Question 43

drugs tend to distribute into ____ compartments or ____

Answer 43

fluid, fat

Question 44

a low Vd means

a high Vd means

Answer 44

the drug stays in ECF, outside cells

the drug stays inside cells

Question 45

Vd can be very large if

Answer 45

a drug accumulates at a specific site outside the blood

Question 46

what is ion trapping?

Answer 46

the side of the membrane favoring the ionized drug will tend to accumulate more drug than the side favoring the non ionized drug.

Question 47

you have a drug that is a weak acid, pKa=3.4. Will the drug more likely be “ion trapped” in the stomach (pH 1.3) or the plasma (pH 7.4)?

Answer 47

in the stomach, the protonated form predominates meaning the acid is nonionized

in the plasma, the deprotonated form predominates meaning the acid is ionized

the non ionized drug will move across the membrane, but the ionized form will exist at a much greater concentration on the plasma side since it promotes ionization

Question 48

you give an acidic drug with a pKa of 2.7 to a cow. Will the drug accumulate in the milk (pH 6.8) or the plasma (pH 7.4)?

Answer 48

the ionized form will predominate in both environments (deprotonated form since pH is higher than the pKa in both locations). But the pKa is further from the pH of the plasma compared to the milk. This means the drug will be more ionized in the plasma than in the milk. This means the total drug concentration will be higher in the milk compared to plasma since more NONionized drug would be in the milk.

an acid is more non ionized in an acid

a base is more non ionized in a base