Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

pharm > Lec3-5 > Flashcards

Lec3-5 Flashcards

1
Q

lipophilicity

A

solubility in lipid relative to water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

lipophilicity is measured by

A

oil/water partition coefficient (drug conc in oil v water)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

drugs with carboxylate reside undergo ionization and become ____
what is their solubility to water and lipid now

A

anions
more soluble to water
less soluble to lipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

drugs with amine undergo ionization and become ____

what is their solubility to water and lipid now

A

cation
less soluble to water
more soluble to lipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

quaternary ammonium with fixed positive charge (such as ACH) has what type of lipophilicity

A

lipophilicity is low
high solubility in water
low solubility in lipid plasma membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

very large MW drugs

A

> 1000 (tend to be proteins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

small MW drugs

A

<1000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

pharmacokinetics is concerned with

A

the time course of

  1. absorption
  2. distribution
  3. eliminiation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

absorption

A

drug from site of administration into the blood stream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

why is conc of plasma important

A

bc it’s what we can measure (blood)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

distribution

A

from blood stream into tissues in body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

elimination

A

getting out of body in form of molc it was administered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

4 major types of biotransport

A

passive diffusion throguh plasma membrane
filtration
carrier-mediated transport
receptor-mediated endocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what order kinetics is passive diffusion and is the half life or rate dependendant on dose conc

A

first order
half life NOT dependent on conc
rate IS dep on conc gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

transport in bulk flow of aqueous fluid is known as

A

filtration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

filtration rate is dependent on ? (3)

A

hydrostatic pressure
MW, size, charge
tissue porosity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what type of transport can be active transport of a molc that wouldn’t cros w/o it

A

carrier-mediated transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

drug transporter whose efflux pump causes resistance to some antitumor drugs

A

MDR p-glycoproteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

biotransporter that is important for big molecules

A

receptor-mediated endocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

rate of receptor mediated endocytosis is dependent on

A

receptor expression and membrane insertion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what protein therapeutics is receptor-mediated endocytosis a mechanism for

A

monoclonal antibodies (iGg)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

time course of transport from site of administration to systemic circulation

A

absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

bioavailability is the

A

% dose absorbed (what % gets into bloodstream)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

only route of admin that’s 100% bioavailabity

A

intravenous bc all put into vasculature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

route of admin with fastest possible input rate

A

intravenous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

during subcutanrous or intramuscular routes of admin where do low MW lipophilic drugs enter
where do high MW compounds enter

A

low - into blood

high - into lymphatics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

subcutaneous and intramuscular has better biovailability than ____ for ____ drugs

A

than oral route

for polar & high MW drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

during inhalation route of admin, rapid absorption of gases and vapors is due to

A

high pulmonary blood flow

low diffusional distance from alveolus to blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

which route of admin do we want no bioavailability

A

inhalation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

why is absorption through skin (topical route) generally slow

A

moves through surface layers of dead, keratinized cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

which route avoids the first pass effect

A

topical (i.e. transdermal)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

why might bioavailabity of oral route be low

A 
mucosa as barrier
high MW
low lipophilicity
carrier-mediated extrusion
first pass effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

biotransformation during the absorption process

A

first pass effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

is bioavailability low or high in a drug with NO first pass effect

A

high bioavailability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

time course of transport from vasculature to tissue space

A

distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what determines equilibration rate during distribution

A

blood flow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

highly perfused organs?
intermed?
low?

A 
high: 
lung 
liver
brain 
kidney

inter:
skeletal muscle

low:
fat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

which is equilibrated faster? highly perfused structures or low

A

highly bc equilibrate in mins while low does in hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

determinants of equilibrium gradient in distribution

A

vascular permability
macromolc binding in plasma and tissue
MW, lipophilicity, carrier affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

BBB has what 2 things that allow drugs to pass

A

tight junctions and transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what does a drug binding to albumin do & whats its effect on equilibrium gradient

A

it prevents the complex from moving out of the vascular compt
as drug distributed, dissociated from albumin and incr drug distribution (high equilibrium gradient)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

monoclonal antibody likely to distribute into a space like that of

A

albumin (in plasma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

volume of the body into which the drug appears to have distributed once equilibrium is obtained

A

volume of distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

(plasma) concentration is

A

amount (g) / volume (L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

volume of distribution is determinant of

A

plasma concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

one compt model v 2

A

1 compt - drug ditributes entire volume and reaches equilibrium v quickly

2 compt - equilibrates slowly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

high lipid solubility means ____ Vd

A

high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

high MW(proteins) - ___ Vd
small MW and polar(charge) - ____ Vd
small MW and lipophilic - _____ Vd
highly lipophilic and accumulates in fat - ____ Vd

A

small (Vd about plasma vol, 4%)
Vd like sucrose (Vd about extracell fluid vol, 17%)
Vd like water (Vd about total BW, 58%)
more than body water (»58%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

mechanism by excretion or biotransformation

A

elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

molc in same chemical configuration as the form it was injected in is by

A

excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

clearance is what over what

A

volume of plasma cleared over unit time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

what is the extraction ratio & what is it’s range of values

A

Cp arterial - Cp venous
0=nothings removed
1=all of drug is removed

53
Q

what determines the elimination rate of a drug from the body

A

total clearance

54
Q

elimination rate (amt of drug in body/time) =

A

Cl Total x Cp

where Cp=plasma conc

55
Q

elimination rate changes in parallel w

A

plasma conc

56
Q

total clearance = sum of

A

renal and nonrenal clearance

57
Q

renal clearance refers to

nonrenal

A

urinary excretion unchanged

all other routes and mechanisms

58
Q

nonrenal clearance participates in biotransformation where critical enzymes are lumped into phase 1 and phase 2
-whats the general difference

A

1- oxidation, reduction, hydrolysis

2-conjugations

59
Q

pathway of biotransformation

A

drug –phase 1 –> metabolite –phase 2–> conjugated metabolite

60
Q

main enzyme for phase 1

A

CYP450

61
Q

2 isozymes of CYP450

A

3A4 and 2D6

62
Q

how do CYP450 familu isozymes differ

A

substrate specificity
inducers
inhibitors

63
Q

what happens to clearance of some drugs when theres biotransfortmation w an inducer

A

increases clearance

64
Q

what are good ligands for phase 2 conjugation

A

OH

65
Q

good ligands for phase 1

A

CH3

66
Q

phase 2 conjugating MOieties (6)

A 
GMS GAG
glucoronic acid 
methyl groups
sulfate
glutathione
acetyl group
glycine
67
Q

phase 2 enzymes that are transferase creater metabolites with ___ compared to parent

A

higher MW

68
Q

volume of plasma cleared by excretion unchanged into urine

A

renal clearance

69
Q

mechanisms of renal clearance

A

Glomerular filtration of unbound low MW drug
prox tube secretion mediated by oatp and mdr
passive reabsorption of uncharged, lipophilic drug

70
Q

why is renal clearance small

A

bc readily reabsorbed

71
Q

equation for renal clearance

A

urinary excretion rate / Cp

Cp=plasma conc

72
Q

if renal clearance is 0-120 (

A

not filtered and/or lots of reabsorption or bound to macromolc in plasma

73
Q

if renal clearance is 120 (GFR) it’s mechanism of excretion was

A

filtration and NO reabsorption

74
Q

if renal clearance is 120-640 (RPF) it’s mechanism of excretion was

A

filtration and secretion
NO net reabsorption
*>GFR only happens if secreted into nephron in prox tubule and no net reabsorption

75
Q

renal clearance is most likely what for:

high albumin binding

A

<120

76
Q

renal clearance is most likely what for:

lipophilic drug

A

<120

filtered but reabsorbed

77
Q

renal clearance is most likely what for:

acidic drug w affinitiy for OATP, high urine pH

A

> 120
OATP means likely to be secreted so incr ClR
if drug is anion (wk acid) then it’s more charged in high pH –> less reabsorption –> incr ClR

78
Q

renal clearance is most likely what for:

acidic drug w low urine pH

A

<120

would want a more basic pH if drug is acidic

79
Q

what type of distribution? drug rapidly equilibrates into volume of distribution

A

single compartment distribution

80
Q

type of elimination?
drug is cleared at constant fractional rate
Kel (elimination constant) is fraction eliminated per unit time

A

first order elimination

81
Q

does total clearance depend on dose

A

no

82
Q

how do you linearize plasma conc

A

take ln

83
Q

bioavailability with iv

A

100%

84
Q

compute vol of distribution

A

dose/Cp0

85
Q

elimination half life is function of both

A

Vd and clearance

86
Q

tiem to eliminate 50% of a drug from plasma

A

half life

87
Q

is half life dose depend or independ? what order of elimination?

A

dose independent

first order

88
Q

if you incr Vd what happens to half life

A

larger Vd –> lower Cp0 –> (longer or) incr half life

89
Q

increase clearance what happens to half life

A 
faster clearance (higher ClT) so shorter half life
* no effect on CP0
90
Q

how are Cp, Vd, ClT, and half life affected with dose

A

Cp incr w dose

rest do not change

91
Q

with iv admin, 1st order elimination, 1 compt distribution, rapid reversible effect, and no active metabolits

if you double dose, what happens to duration

A

duration increases by addition of one half life

92
Q

what type of elimination has Cp v time as linear without log transformation

A

zero order

93
Q

in zero order kinetics, how does biotransformation time change w conc

A

50% biotransformation time incr w conc

94
Q

main diff bn first ortder and zero order Cp v time

A

first order has fractional elimination like it decr by half

zero order has constant rate of elimination like decr by 20 every hour

95
Q

is eliminiation happening from the central or peripheral compt? what are central organs? peripheral?

A

central

central: lung liver kidney brain
peripheral: fat and skeletal muscle

96
Q

Cp v time curve for two compt model has 2 phases, what are they and what do they describe

A

alpha - initial rapid decline that describes distribution of drug from central in peripheral comp
beta - linear

97
Q

which most similarly acts/looks like the plasma conc v time curve of a 2 compt model? highly perfused or poorly perfused tissue concentration

A

highly perfused tissue (central compt like brain)

98
Q

what happens to conc of poorly perfused tissue as Cp decreases

A

they rise/ incr til reach equilibirum

99
Q

duration of action for multi-compartments is dependent on

A

distribution into and out of compt where target is located

100
Q

what do lipophilic drugs that act in the brain duration of action depend on

A

redistribution out of brain to slowly perfused tissues

**not on elim by kidney or liver

101
Q

can duration of action be short if elimination half life is long

A

yes

102
Q

half life is always elimination

A

false theres an absorption half life

103
Q

plasma conc time curve is influenced by what 3 things

A

absorption rate constant
elimination rate constant
bioavailability

104
Q

the faster the absorption (i.e. the shorter the half life of absorption), the ___ Cp max and the ____ t max

A

higher Cp max

earlier the tmax (so the time for that peak is shorter)

105
Q

fraction of dose that gets into plasma conc is known as

A

bioavailability

106
Q

what is proportional to bioavailability

A

area under the curve of Cp v t

107
Q

integral of Cp = AUC = ?

A

Fx D / ClT
bioavailability x dose / total clearance
*ClT is constant

108
Q

the absolute bioavailability is determined for

A

a new drug

109
Q

the relative bioavailability is determined for

A

generic in comparison to proprietary formulation of drug

*comparing one manufacturers formualtion to anoteher

110
Q

eq for absolute bioavailability and relative

A

abs: AUC nonIV dose / AUC IV dose
rel: AUC formualtion 1/AUC formualtion 2

111
Q

during continuous infusion, at steady state what 2 rates equal each other

A

input rate = output rate

112
Q

input rate =

A

Cp steady state * ClT

*also true for output rate equation

113
Q

equation that relates Cpss w infusion rate

A

Cpss=infusion rate / ClT

114
Q

the higher the ClT the ____ the Cpss

A

lower the Cpss

*unless you increase the infusion rate to get a desired CPss

115
Q

tiem to achieve steady state level achieved by infusion depends SOLELY on

A

elimination half life

116
Q

time to reach 50% of Cpss take how many elimination half life

A

one

117
Q

time to reach 93% of Cpss take how many elimination half life

A

four

118
Q

when prescribe a drug by continuous IV infusion, which drug will reach steady state mor quickly? shorter half life or longer

A

shorter half life

119
Q

Cmin is called a

A

trough

120
Q

CmaxSS to CminSS is

A

therapeutic window

121
Q

when is loading dose important

A

for rapid onset of effect is needed

if drug elimination half life is LONG and slowly attains SS

122
Q

diff bn multiple dose kinetics and IV infusion

A

multiple is not continuous, it’s pulsatile

123
Q

equation for multiple dose kinetics

A

maintenance dose / dosing interval

124
Q

extent of accu,ulation from first dose to SS depends on

A

ration bn elimination half life and dosing interval

125
Q

if dosing interval is 7 times the elimination half life, how much accumulation?

A

none

126
Q

if dosing interval = elimination half life, how much accumulation?

A

2 fold accumulation

127
Q

calculate Cp average

A

input rate / clearance

(D/t) / Cl T

128
Q

compare the Cp avg of small dose at frequent intervals and high dose at long intevals

A

they’re about the same

pharm (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions