midterm 1 Flashcards
(122 cards)
1
Q
what is manner in whihc drugs are taken?
A
dosage regimen
2
Q
Definien pharmacokinetics
A
the stuyd of the fate of drug in the boyd
focus on:
ADME
3
Q
define pharmacodynamisc
A
the effct of a drug in the body
- drug and recptor
- physiochemical or biochemical effects
- interaction of the drug
4
Q
why study pharmacokinetics?
A
therpautic window
5
Q
time course of a drug in body
A
drug in - plasma - receptor - intensity of effect - drug out
6
Q
how do we meadure concentrations of drugs in blood
A
urine or blood
7
Q
what assumptions do we make for one compartment model
A
- instanteous distrubution
- elmination and transpot follow firts order kinetics
8
Q
what is the rate of change in the body dependent on?
A
- how much drug in reservois
- how well the drug is eliminated
9
Q
how much drug is in resefovir depends on what?
A
- size of reservoir
- dose given
10
Q
how well drug is eliminated depends on what?
A
- rate of elimination
- capacity of elimiating organs to remove drug
11
Q
whats Cp0h
A
initial cocnentration
12
Q
calcte of Cp0h
A
dose/ VD
13
Q
what are the indpednet values?
A
Vd, CL, and dose
14
Q
what does a large Vd indicate?
A
extensive distribution
15
Q
path of a polar dug in body
A
stays in blood, low Vd
16
Q
path of a weak base in body
A
lipophilic drug - has affinity for tissues therfore Vd is high
17
Q
whats the samllest VD
A
plasma volume
18
Q
types of elimination
A
- zero - order
- first order
19
Q
elimiantion constant with time is what type?
A
zero order
20
Q
what is k0
A
zero- order elimiantion rate constant
21
Q
how do we expect zero order to look on linear vs semi-log paper
A
liner - straight line down
semi-log - curve down
22
Q
whats a passsice diffusion - relate to order process, energy, driving force and species, competion and saturbilibyt
A
- first order
- no energy
- driving force: gradient concentration
specie: unionized - competition none
- satuability none
23
Q
whats a active diffusion - relate to order process, energy, driving force and species, competion and saturbilibyt
A
- zero order
-energy - driving force: carrier
specie: unionized or ionized - competition
- satuable
24
Q
what is the rate of change in first order depednet on
A
K - eleimintion cinsant
and Concentration
25
what does first ordeer look like on linera vs semi log parp
liner- curved
semi-log - straight
26
unit for K
time-1
27
what is half life
the amount of time needed for a drug to drop to half it's concentration
28
is half life consant or fluctutaion in first order?
consntnt
29
is half life consant or fluctutaion in zero order?
fluctuating
30
what is terminal half-life?
half-life of elimination phase
31
how long does it take for the body to be ride of 90% of a drug?
3.3 half lives
32
is K constant in zero order kinetics?
No
33
how do we calcaute half life
-.693/ K
34
what does AUC show?
total systemic exposure of the body to the drug
35
if we have high systemic exposure how would we expevct AUC to respond?
high AUC
36
units of AUC
amount*time/volume
37
CL units
volume/time
38
how can we get CL?
1. K time VD
2. Dose/AUC
39
using VD, CL what can we find?
half life, AUC, C0, K
40
tissues have their own make up whihc relates to what ocnepcts?
1. blood flow
2. cellualr makeup
41
what makes tissue less perfused?
high cell lipid cocnentration
42
what makes the tissue more perfused?
large concentration of durg metabolized by enzymes
43
when atlking about two compatrment models what are the two pirinicple steps?
distribution and elimination
44
how does Iv bolis in a two compatrment look
hockey stick
45
iv bolus in a one comeptment
just line decreasing
46
in a two-compartment where does blood travel first? then where? what are the elmination conatnts between trevel?
central compatment - blood Cp
Peripherla tissues - Ct
Cp- Ct k12
Ct - Cp k21
Emlimination from central comaptrment k 10 (K)
47
how do we travel between compartments?
via the concetration gradient
48
what is pseudoequilibirum
constnt ratio between drug in central and peripheral compartments
49
if we are trying to gage the cocnentration of a drug with it's receptor in the central compatrment what is useful?
the plasma concentrations before or after pseudoequilibirum
50
if we are trying to gage the cocnentration of a drug with it's receptor in the periphaerl compatrment what is useful?
the plasma concentration only after pseudoequilibirum
51
organs of central compatrment
plasma, liver, kidenys
52
organs of pheripheral compartments
brain, musscle, adipose tissues
53
for two compartment Iv bolus what's an equation we can use to find concentration at a given time
C= A(to the power of -alpha time) + B(to the power of -beta time)
54
distrubutaion phase is denoted by whihc greek alphabet
alpha
55
elminaition phase is denoted by whihc greek alphabet
beta
56
why would we feature in Iv bolus two compartment?
to find alpha of distributaion phase
57
when i feater in iv bolus two compartment where is my A intercept
highest point where distrubution began
58
how long does it take to reahc 90% of psuedo equilibirum?
3.3 half lives
59
VD in central comaprtment calc ve in peripherla compartment calc - find on the formula sheet
slide 11
60
Compartment model pros
-simplified approach to describe ADME
- monitor quantitivaly drug levle with urine or blood test
- can extract information
- useful for comaprison of pharmacokinetic agesnt
61
Compatrment model cons
- is empirical lacking ohysiological relevance
- physiological models more relaistic
-
62
when does drug cocnetration in the body decline?
when no more input
63
what order of elimiantion does IV infusion follow and why?
zero - constant bc constant input
64
what is steady state define as?
rate of input equals rate of output
65
in iV ifsuion do we have a caontnt elemination rate?
yes it's called K
66
what dose k0 stand for? also denoted as ?
zero order input - rate of insusion can aslo be denoted as R
67
at steady state does plasma cencetraion change?
no plasma concnetrtaion is constant at this point
68
by defintion when can we assume we have reached steady state?
when 95% within Css
69
what determines when we reach CSS
input is constant thus it depends of output of drug
70
the time it takes to reach Css depends on what?
half-life whihc is a fucntion of output elimination
71
how many half lives does it take to reach Css
3-5
72
when Iv infusion is stopped how does elimination of drug orccue
in a firts order fashion
73
what is the need for featuring in iv infusion?
it allows us to find the emlimination rate (K) for when insuion is stopped
74
what equation is used for determining elmination once Iv infusion is stopped?
formula sheet change in C
75
why would we need a laoding dose?
iv infusion takes 305 half lives to reach steady state however by using a loading dose we can increase the speed with whihc Css is achived
76
when is infusion used?
- emergmy
- when other dosage forms are not tolerated
- skips absorption step so quicker
77
how do we calcualte loading dose?
slide 15 lecture 3
78
most of the IV infusion we discuss is one or two compatment?
one compartment
79
although the distrubution phase in Iv bolus is clearly define we don't have a distributaion phase per say for iv infusion why?
in IV bolus all drug flow into cnetral compartment and distrubutes ti periphery. howeerv in infusion since there is a consnt drug suppply both central and periphery already have drug when infusion is stopped therefore there is a less sudden dip in drug level through out body since it's already distrubuted however in Iv bolus disturbutaion still has to occur
80
how does time to steady state change for iv infusion multi compartment
the equestion is still Css= (k0/ K X VD)
however the Vd must be that of the central comaprtemnt
81
if we have a LD in Iv infuion mult compartment what will it look like ? what does it look like normally?
- hockey stick - up down up
normally one curve downwards starting from top
82
what is Css level dependent on?
VD and CL parameters ZZ
83
when are IV bolus and infsuion reserved for?
- emergency when we need high drug concenn trations or rapid onset of action
84
how are most drugs admintered? examples
through extravastion means sc, im, enema, supppository or oral ingestion
85
what is the most commone route of adminstartion?
oral
86
key step involved in oral?
absorption
87
what elimination order is orla
first- order kinetics
88
factors determing release and absorption of drug following oral adminstration of solide dosage form
1. release characteristics of dosage form - disintegration, dissolution
2. physiochemialc characteristics of drug
3. physiology of GI tract
4. abnormalities and disease of GI tract
89
outline the path a oral drug takes through body
drug in product -(dissolution) - drug in solution - (intestinal absorption) - absorbed through drug in portal vein - active drug in systemic circulation
90
what steps can limit rate of absorption?
1. dissolution
2. intestinal absorption
91
what order processes are dissolution and disintegration?
first-order processes
92
how does absorption in gut determine extent of absorption?
gut is very acidic, most absorption happens in intestines
however surface arae, pH and permebility play a role in absorption
93
how does gastric emptying affect absoprtipn?
most drug are absorbed in intestine so we want fast gastric emptying
having slow gastric emptying can effect extent of absorption of other drugs
94
what kind of foods can delay gastric emptying
fatty foods
95
what factor is tied closely to first-pass effect?
oral biovailibility of drug or F
96
how is F determined?
the systmeic drugs abvaialibilty determined determined by gut and hepatic clearnace
97
define F
total fraction of doses that escape various barriers before entering systmic circualtion
98
what value is F usualy
below 1
99
What are the usual barriers we measure escaping?
gut
hepatic
feces
100
effect of P-glycoportain or CYP450
lots of drugs are broken down by CYP 450 and my drinking grapefruit juice we inhibto this so drug can't be broken down as easiy and there is lots in circulation
101
what does oral admin grpah look like
start at zero then clim up to the point where ka=K and then gradual decline from that point
102
before the peak of the oral admin curve what processes are occurring
absorption phase - consists of ka and K
103
after the peak of the oral admin curve what processes are occurring
elimintaion - K
104
when grpahing what's on the x axis? Y axis?
time
concentration
105
for oral explian a one compartment model of how the drug goes thru the body
drug (D) - passes through ka - into the plasma (Dp) - then is excreted (K)
106
what is the rate of change defined by in the body for oral
rate of input - rate of output
input = D * ka
Output = K *Dp
107
what is ka
absorption rate
108
what is the intial C0 of a drug via oral
0
109
what is Cmax represent in oral
where rate of absoprtion = rate of elimation
110
what is t max depenedent on
drug in and drug out
indepednt from concentration
111
how does chnages in the ka affect AUC?
doesn not effect
112
how do chnages in the K effect AUC
inversely ralted
113
why feature in oral dosing?
to determine the ka
114
what is the flip flop phenomena?
when absorption ios slower then elmination (K) therefore the iv line intersects the oral line
115
what does ka < < K mean?
this is extended or controlled release formulation meaning the rate of input is slower
116
why is iv nescessary in oral grpahs
the Iv allows us to tell whether the terminal phase of the graph represents ka or K
117
if ka>> K
so iv is not parllry to terminl phase what does the terminal phase tlel us?
the terminal phase is then ka
118
how do we determine that the terminal phase is K (elimination)?
we look at the iv in comparasion to the po.
if iv line is paralle to po then that is the K, otheriwse it's the ka
119
what is CLtb vs CLo?
CLtb - total body
- this takes into account F
- if iv F is 1, if oral we have a value
CLo - oral
- can get if we don't know our F
120
if we don't know our F what clearance do we get?
CLo
121
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