exam 3 Flashcards
(129 cards)
1
Q
ADME stands for
A
Absorption, Distribution, Metabolism, Excretion
2
Q
Characteristics determined by concentration vs time profile
A
Onset, duration, intensity
3
Q
Time between administration and pharmacological effect
A
Onset
4
Q
How high the concentration is
A
Intensity
5
Q
Length of time above MEC
A
duration
6
Q
Minimum effective concentration
A
MEC
7
Q
The study of the absorption, distribution, biotransformation, and elimination of xenobiotics
A
Pharmacokinetics
8
Q
The study of the molecular, biochemical, and physiological effects of xenobiotics and their mechanisms of actions
A
Pharmacodynamics
9
Q
Patho, pharmacodynamics, pharmacokinetics make up
A
pharmacotherapeutics
10
Q
Most rapid onset route
A
Intravenous
11
Q
Slowest onset route
A
Oral
12
Q
Routes of administration
A
Ingestion, Inhalation, Dermal, Parenteral
13
Q
IV, SC, IM, Intraperitoneal equal what route
A
Parenteral
14
Q
Reduction of absorption impacts
A
intensity and duration
15
Q
Reduction of speed of entry impacts
A
Onset
16
Q
AI phenobarbital to hydroxyphenobarbital
A
Hydroxylation
17
Q
AA procainamide to N-acetylprocainamide
A
acetylation
18
Q
IA codeine to morphine
A
demethylation
19
Q
AR
A
acetaminophen to reactive metabolite
20
Q
Major routes of excretion
A
Renal (kidney) is primary
Biliary (feces)
21
Q
Other routes of excretion
A
Pulmonary, salivary, mammary
22
Q
Which antibiotic is a better choice in a patient with renal failure?
A
The one eliminated in bile not urine
23
Q
Barriers that may reduce amount of drug that reaches site of action
A
gut wall metabolism, degraded in stomach, dose distributing away from target tissue, can’t enter membranes, enzymes
24
Q
The fate of a drug once it enters the systemic circulation
A
Disposition
25
A chemical that is normally foreign to the body includes drugs, occupational chemicals, environmental compounds
Xenobiotic
26
___ percent of problems used to be from ADME, now its ___ percent
40%, 10%
27
___ barriers like the BBB can significantly reduce the amount of drug that enters the site of action
Tissue
28
Morphine is a metabolite of codeine and this metabolite is responsible for the analgesic effect when codeine is administered. In a patient who has a genetic defect such that they cannot metabolize codeine, the magnitude of pain relief would be expected to be _____ compared to normal patients.
Decreased
29
Factors that determine movement of a drug across membranes
Characteristics of membrane, mechanism of passage, swell time, physiochemical characteristics, pH of microenvironment, surface area
30
Why does most oral drug absorption occur in the small intestine?
Inner wall of small intestine covered by folds of kerckring plicae circulares, surface contain tiny villi and microvilli that increase surface area
31
food transit time in mouth
1 min
32
food transit time in esophagus
4- seconds
33
food transit time in stomach
2-4 hours
34
food transit time in small intestine
3-5 hours
35
food transit time in colon
10 hours to days
36
Carrier mediated transport examples
Facilitated diffusion and active transport
37
95% of drugs are absorbed by
passive transcellular diffusion
38
Transcellular permeability can be increased by
removing charged ionized groups, increasing lipophilicity, reducing size
39
The passive movement of drug through lipid membranes driven by concentration gradient
Transcellular diffusion
40
The passive movement of drug between cells via tight junctions driven by concentration gradient
Paracellular diffusion
41
A carrier mediated process that involves a transport protein which moves drug with a concentration gradient
facilitated diffusion
42
A carrier mediated process that involves a transport protein which moves drug against a concentration gradient
active transport
43
A process in which a cell engulfs and internalizes a particle
Endocytosis
44
Primary site of absorption after oral administration because of high surface area
small intestine
45
altered by food or drugs, influences extent and rate of drug absorption
gastrointestinal transit time
46
carrier mediated is different than passive because its
saturable and subject to drug drug interactions
47
Selectively move substrates across cell membranes
transporter proteins
48
remove drugs from cells that have entered via passive diffusion, can reduce the amount of drug that accumulates in certain tissue such as the brain
Efflux transporters
49
Slowing gastric emptying would be expected to have which effect on the absorption of a drug absorbed by passive diffusion?
it will take longer to reach peak concentration
50
Which moves mechanisms down a concentration gradient?
Paracellular, transcellular, facilitated diffusion
51
Co-administration of an inhibitor of the efflux protein p-glycoprotein would have what effect on the oral absorption of a drug that is a substrate for pgp?
The inhibitor will increase the amount of drug absorbed
52
which of the following would not increase transcellular permeability? remove ionized groups, decrease lipophilicity, reduce molecular size
decreasing lipophilicity
53
under passive diffusion rate of transport increases as concentration _____
increases
54
move solutes out of the cell
efflux transporters
55
Consequences of efflux transporter p glycoprotein
Limited drug absorption, enhanced drug elimination, limited distribution
56
For large molecules, depend on particle size, frequently used for nanoparticle drug delivery
endocytosis
57
The movement of drug molecules across biological membranes into various tissues in the body
Distribution
58
The movement of drug molecules across vascular endothelial cells and into interstitial space
Transvascular transport
59
A transvascular transport process driven by pressure
Convection
60
A transvascular transport process driven by a concentration gradient
Diffusion
61
The concentration of a drug within a tissue due to pH differences that lead to ionization of the drug in the tissue environment
drug trapping
62
The initial movement of drug from highly perfused tissues to poorly perfused tissues
Redistribution
63
slower distribution, driven by pressure, convection
perfusion
64
driven by concentration gradient, diffusion
permeability rate limited
65
binding of drug to plasma protein
restricts distribution
66
most drug in tissue is bound to
nonspecific sites and not receptors
67
only ___ is phamacologically active
free drug
68
different ph environments causes
drug trapping
69
BBB properties
tight junctions, negative head groups, high pgp concentration
70
how drugs enter cns
existing transporter, directly to CNS, disruption of BBB, appropriate physiochemical properties
71
efflux activity can be so extensive drug in brain doesnt reach
measurable concentrations
72
___ molecules dont cross membrane to fetus
large polar
73
driving force for convection
pressure
74
driving force for diffusion drug movement
concentration gradient
75
A drug that is only distributed into vascular space will exhibit a monoexponential blood concentration vs time curve after intravenous administration t of f
true
76
Which drug is most likley to undergo transvascular transport via convection
the biggest dalton one
77
A decrease in plasma protein binding will result in an
increase in amount of drug in tissue (only free drug crosses)
78
A change in the structure of a drug molecule such that is is no longer transported by pgp will have what effect on CNS concentration?
higher cns concentration (pgp only transports out bc its efflux)
79
Kidney route excretion process
GABEPVDC
80
Mechanisms of renal excretion
Filtration, active tubular secretion, tubular reabsorption, biotransformation
81
Determinants of filtration
MW <5000, number of nephrons, protein binding, renal blood flow
82
Filtration happens in
glomerulus of bowmans capsule
83
test for renal disease
if protein in urine then its a sign of disease
84
Active tubular secretion location
Proximal convoluted tubule
85
active tubular secretion graph
linear then hits a max
86
drugs that under go ATS an exhibit
Stereoselective renal secretion
87
clearance vs mw relationship
indirect
88
dose and urinary excretion relationship
indirect
89
The active transport of drug from blood to renal tubule in proximal tubule
active tubular secretion
90
Movement of solute from inside renal tubule back into the blood
tubular reabsorption
91
reabsorption of drug from small intestine after drug has been excreted through bile into intestine
enterohepatic recirculation
92
food stimulates release of bile with drug in it
dose dumping
93
Primary routes of drug excretion
renal and hepatic
94
secondary routes of drug excretion
pulmonary, salivary, mammary
95
Most important mechanisms of renal excretion
filtration, active tubular secretion, tubular reabsorption sometime biotransformation
96
glomerular filtration is largely influenced by
molecular size and plasma protein binding
97
Drugs which undergo active tubular secretion exhibit
saturation at high concentration and subject to competition
98
tubular reabsorption is passive and driven by
concentration gradient and ph sensitive
99
carrier mediated tubuar reabsorption
process is saturable
100
hepatic elimination involves
metabolism and biliary excretion
101
when a part of a dose is eliminated before entering circulation
first pass effect
102
pgp and mdr1
actively secrete drug from hepatocyte into bile
103
primary factors determining biliary secretion are
molecular weight and polarity
104
Which is most likely subject to competitive drug drug interactions
tubular secretion
105
As mw increases in renal elimination, filtration
decreases
106
plot mw and drug excreted in bile
direct relationship
107
Effect of enterohepatic recirculation on half life of a drug
increases half life
108
decrease in plasma protein binding in glomerular filtration results in
increase of renal elimination
109
which vitamin undergoes bioactivation in the kidney
vitamin d
110
phase 1 metabolism
biotransformation of xenobiotics that includes oxidation, hydroxylation, to introduce or expose a functional group
111
phase 2 metabolism
involves conjugation with a polar group yielding a polar metabolite that can be excreted in bile or urine influenced by availability of co substrate
112
Most important organ where biotransformation takes place
liver
113
frequently but not always subsequent to phase 1
phase 2
114
two components in cytochrome p450 system
cyp450 reductase and cyp450
115
indentification of cyp450 important for predicting
drug drug interactions
116
cyp450 generates
reactive oxygen species with detrimental cellular effects
117
critical determinant in ability to bind to cyp450 and binding affinity
geometric shape/conformation
118
potent inhibitors of cyp450 that serve as sixth axial ligand for iron in heme
nitrogenous compounds
119
covalent binding renders cyp450 inoperable and new cyp450 must be synthesized to restore metabolism
mechanism based inhibitors, suicide inhibition
120
induction of metabolism results from
activating transcription factors
121
when drugs induce the same cyp450
autoinduction
122
inducers of drug metabolizing enzymes exhibit
cross talk
123
increases polarity and size of drug molecules and reduces pharmacologic effect
phase 2 metabolism
124
variablity in diet, other drugs, disease, environment can be more important than
genetic variability
125
which pathway increases mw
phase 2
126
which pathway results in metabolite eliminated in bile
phase 2
127
Which inhibits cyp4a4
ritonavir
128
what type of cyp450 inhibitor produces the longest lasting inhibition
mechanism based inhibition
129
inducers of cyp450 are selective for one enzyme or enzyme family t o f
false
