Test 2 - definitions

Question 1

3 major physiologic factors that affect drug distribution

Answer 1

blood flow, body composition, protein binding

Question 2

3 major drug factors that affect drug distribution

Answer 2

lipophiliicity, size, ionization

Question 3

2 major plasma protiens

Answer 3

albumin & alpha 1 glycoprotien

Question 4

albumin

Answer 4

prefers acidic binding & hydrophobic; typically constant levels

Question 5

alpha 1 acidic glycoprotien

Answer 5

binds to basic drugs; stressed induced

Question 6

plasma protein binding is ___ & ___

Answer 6

saturable and reversible

Question 7

amount of drug bound to a plasma protein is determined by

Answer 7

drug concentration, # of available binding sites, affinity of drug for protein

Question 8

what causes pharmacological effect

Answer 8

free drug

Question 9

ion trapping

Answer 9

when an ionized species of drug accumulates in a specific tissue or organ, more drug ionized on one side than the other, accumulation of drug in a specific tissue that doesn’t reflect the plasma concentration

Question 10

Vd

Answer 10

hypothetical volume; apparent volume of distribution

Question 11

Vd ___ describes _____

Answer 11

indirectly; the extend to which a drug distributes outside of the plasma compartment which is one of the water compartments within the body; proportionally constant related to the amount of drug in the body to the plasma concentration

Question 12

Vd is a ____ pharmacokinetic paramater

Answer 12

independent; it is dictated by the characteristics of the DRUG such as ionization, lipophilicity, size, etc

Question 13

Vd is always a ___ divided by ___

Answer 13

mass over volume

Question 14

C0 must be assumed to be

Answer 14

instantaneous distribution

Question 15

total body water = __ X body weight

Answer 15

.6

Question 16

ECF = __ X body weight

Answer 16

.2

Question 17

ICF = ___ X body weight

Answer 17

.4

Question 18

ECF = ___(3/4) & ___(1/4)

Answer 18

Interstital fluid / Plasma

Question 19

Vd (once divided by kg): less than .6 = drug in ___ more than .6 = drug in ___

Answer 19

plasma tissues

Question 20

smaller Vd means more drug is in the

Answer 20

plasma bc of protein binding

Question 21

pericytes

Answer 21

have tight junctions between cells to limit diffusion of drug into CNS

Question 22

PgP also work to

Answer 22

pump out toxins and drugs from the brain

Question 23

what could hinder a drug from passing through BBB

Answer 23

large, charged, hydrophillic

Question 24

metabolism

Answer 24

refers to the process by which the administered drug is biochemically altered producing a metabolite

Question 25

metabolites typically have ___ activation

Answer 25

little but some can have significant

Question 26

pro-drug

Answer 26

inactive but upon metabolism release or form active drug

Question 27

excretion

Answer 27

removal of drug from body

Question 28

\_\_\_ is the primary organ for excretion

Answer 28

kidney, but some drug can be eliminated through bile

Question 29

when a drug is renally excreted, we mean that ____ is eliminated

Answer 29

unchanged parent drug

Question 30

the purpose of drug metabolism is to

Answer 30

increase water solubility, increase polarity, and increase H-bonding partners

Question 31

hepatocytes work through what 2 functions

Answer 31

passive diffusion & carrier transporters

Question 32

OATP enzymes

Answer 32

shuttle drug across membrane into hepatocye taken from GI tract

Question 33

MRP1 / P3 / P4 ABCC1 / C3 / C4

Answer 33

work to shuttle drug out of hepatocyte into the blood stream

Question 34

MDR3 / R1 / P2 ABCB4 / B1 / C2

Answer 34

filter blood into bile canaliculus for excretion

Question 35

what are the two types of hepatic metabolism

Answer 35

Phase 1 and phase 2

Question 36

phase 1

Answer 36

introducing or exposing a functional group to increase polarity; these can be redox, hydroxylation, hydrolysis typically removing methyl and adding NH or OH to prepare metabolite for phase 2

Question 37

phase 2

Answer 37

conjugating reactions, adding a molecule or large functional group, hydrophilic

Question 38

CYP450 are examples of phase 1 or 2

Answer 38

1

Question 39

UGT are examples of phase 1 or 2

Answer 39

2

Question 40

CYP450 enzymes

Answer 40

involved in many biochemical reactions involving endogenous substrates, including steroids, fatty acids, prostaglandins, and bile acids. they are critically involved in the removal of drugs, carcinogens, insecticides, plant toxins, and environmental pollutants

Question 41

CYP2D6 2 represents ___ & what percent homology D represents ___ & what percent homology 6 represents ___ & what percent homology

Answer 41

family (40%) subfamily (55%) gene product (different unless identical)

Question 42

CYP1, CYP2, CYP3 substrates?

Answer 42

drugs, other xenobiotics

Question 43

CYP4, CYP5, CYP8 substrates?

Answer 43

fatty acids, prostaglandins, thromboxanes

Question 44

CYP7, CYP11, CYP17, CYP21, CYP24, CYP27 substrates?

Answer 44

steroid hormones

Question 45

what CYP accounts for 34% in drug metabolization

Answer 45

3A4/5

Question 46

1A1, 1A2, 2E1, 3A3, 3A4,5

Answer 46

nutrition

Question 47

1A1, 1A2

Answer 47

smoking

Question 48

2E1

Answer 48

alcohol

Question 49

1A1, 1A2, 2A6, 2B6, 2C, 2D6, 3A3, 3A4,5

Answer 49

drugs

Question 50

1A1, 1A2, 2A6, 1B, 2E1, 3A3, 3A4,5

Answer 50

environment

Question 51

1A, 2A6, 2C9,19; 2D6, 2E1

Answer 51

genetic polymorphism

Question 52

phase 2 relationship to CYP

Answer 52

phase 2 occurs after CYP450 has metabolized drug but can also work independently of phase 1

Question 53

phase 2 almost always

Answer 53

inactivated the parent drug molecule, but there are some instances where a phase 2 metabolite could still have activity

Question 54

excretion by the kidney is determined by what 3 factors

Answer 54

filtration reabsorption secretion

Question 55

filtration

Answer 55

occurs in glomerular capillary; cut off point is 5000 daltons

Question 56

reabsorption

Answer 56

from filtrate back into the blood happens in the peritubular capillaries (works against drug removal!!!)

Question 57

properties that assist reabsorption

Answer 57

nonionized & lipophilic

Question 58

secretion

Answer 58

from peritubular capillaries into the tubular space

Question 59

properties that assist secretion

Answer 59

lipophilic; transporters

Question 60

amount excreted by kidney =

Answer 60

amount filtered - amount reabsorbed + amount secreted

Question 61

what percent of blood actually gets filtered

Answer 61

20%

Question 62

amount

Answer 62

X, amount given to the patient at the start time of dosing, dose is frequently called X0, mass amount gms, mgs, etc

Question 63

concentrations

Answer 63

C; always amount divided by a volume; mg/L, mcg/mL

Question 64

rate

Answer 64

a change is something per unit time; can be first or zero order

Question 65

rate constant

Answer 65

k, constant rates, do not change with time, determined by slope

Question 66

K for zero order rate is

Answer 66

constant

Question 67

elimination rate in zero order is

Answer 67

constant

Question 68

zero order characteristics

Answer 68

concentration independent elimination; high substrate concentrations

Question 69

K for a first order is

Answer 69

a rate constant

Question 70

elimination rate of drug removal is

Answer 70

variable

Question 71

first order characteristics

Answer 71

concentration dependent elimination; low substrate concentrations