Lecture 2: Pharmacokinetics

Question 1

ADME

Answer 1

absorption
distribution
metabolism
excretion/elimination

Question 2

actions of the body on a drug

Answer 2

pharmacokinetics

Question 3

ionization

Answer 3

many drugs are weak acids

Question 4

partition coefficient

Answer 4

amount in oil vs. amount in water

Question 5

what is the pH in the stomach

Answer 5

1-2

Question 6

will weak acid drugs be ionized in the stomach?

Answer 6

probably not (favors absorption)

Question 7

when pH = pKa..

Answer 7

50% is ionized

Question 8

if a weak acid drug is in a solution 3 pH units below its pKa, almost 100% will be

Answer 8

non-ionized (protonated)

Question 9

pH trapping

Answer 9

drug in stomach, favors absorption
* reaching plasma, gets stuck in plasma because cannot cross back through membrane

Question 10

local anesthetics block _ that carry AP down the axon

Answer 10

voltage-gated Na+ channels

Question 11

a drug molecule must diffuse from _, through _, into _

Answer 11

extracellular fluid, membrnae, cytosol

Question 12

most capillaries are

Answer 12

leaky

Question 13

blood-brain barrier has

Answer 13

tight junctions

Question 14

_ generally enhances ability of drugs to enter brain

Answer 14

lipid solubility

Question 15

metabolism/biotransformation

Answer 15

inactivation of drug by enzymes

Question 16

primary metabolism organ

Answer 16

liver

Question 17

excretion

Answer 17

removal of metabolites or the unchanged active drug from the body
* kidneys (urine)
* liver (bile salts)
* lungs (exhaled)

Question 18

three “families” of cytochrome P450s:

Answer 18

CYP1, CYP2, CYP3

Question 19

subfamilies of cytochrome P450

Answer 19

denoted by letter; speicifc enzymes by number

Question 20

CYP3A4

Answer 20

most common metabolic enzyme involved in drug interactions

Question 21

phase I metabolism

Answer 21

oxidation, reduction, hydrolysis

Question 22

phase II metabolism

Answer 22

conjugation with glucuronic acid

Question 23

zero order drug metabolic reactions

Answer 23

drug concentration does not affect metabolic rate

Question 24

first order kinetics

Answer 24

drug concentration affects rate
* higher conc. = higher rate
* exponential drop in drug concentration

Question 25

factors affecting drug metabolism

Answer 25

* enzyme induction * inhibtion/competition * genetic polymorphisms

Question 26

acetaminophen dose

Answer 26

3 g/day (used to be 4)

Question 27

when does acetaminophen toxicity occur

Answer 27

7-10 g/day

Question 28

signs of acetaminophen toxicity

Answer 28

* initial flu-like symptoms * liver failure: jaundice, decreased blood clotting, death possible

Question 29

antidote for acetaminophen toxicity

Answer 29

N-acetylcysteine

Question 30

prodrugs

Answer 30

administered in an active form * require metabolic activiation by the body

Question 31

codeine is a _ of morphine

Answer 31

prodrug

Question 32

free drug molecules are filtered at the

Answer 32

glomerulus

Question 33

lipid-solible are reabsorbed in _ by passive diffusion

Answer 33

renal tubules

Question 34

ionized (charged) or hydrophilic drugs can't be reabsorbed are therefore excreted in

Answer 34

urine

Question 35

alkalization of urine (increasing pH) will facilitate excretion of

Answer 35

weak acids

Question 36

intrinsic toxicity

Answer 36

* reproducible - all patients at risk * dose-dependent (drug overdose) * sensitivity can vary from patient to patient * result of actions at target receptor or effects at other receptors

Question 37

idiosyncratic

Answer 37

* not widely reproducible * low incidence * occurrence is the result of interaction with patient attributes

Question 38

enteral

Answer 38

administration into the systemic circulation via the alimentary canal

Question 39

parenteral

Answer 39

adminstration into the systemic circulation via routes other than the alimentary canal

Question 40

topical

Answer 40

aministration by direct application onto the skin or associated membranes

Question 40

topical

Answer 40

aministration by direct application onto the skin or associated membranes

Question 41

clearance

Answer 41

a way to collectively quantify all of the processes that make active drug disappear from the body * expressed at the amount of plasma per unit of time that would be completely cleared of the drug

Question 42

volume of distribution (Vd)

Answer 42

theoretical volume in which a drug is dissolved in the body * Vd = D/C0 (dose given/concentration in plasma)

Question 43

half-life (t1/2)

Answer 43

time is takes for drug concentration to decrease by half * 50% of drug is lost in one half-life * 75% lost in 2 * 87.5% lost in 3

Question 44

bioavailability

Answer 44

fractio of original dose that reaches systemic circulation

Question 45

obstacles of oral administration

Answer 45

* variations in stomach emptying time * acidity/alkalinity * interactions with food * absorption across gut epithelium * liver - first pass effect

Question 46

inhibition of P450 enzymes

Answer 46

decreased enzymatic capacity * less metabolism * drug accumulation

Question 47

excretion =

Answer 47

filtration + secretion - reabsorption