Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology > 03&04 - Biotransformation > Flashcards

03&04 - Biotransformation Flashcards

(58 cards)

Start Studying
1
Q

phase 1 reaction result in

A

-relatively minor chemical modification of the parent compound

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

phase 1 reactions may result in the formation of functional groups which serve

A

as site for conjugation rxns

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

phase 1 reaction metabolite formed is more —

A

polar (more water soluble; less lipid soluble)

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

what are phase II reactions

A

these reactions are conjugations (i.e.. synthetic rxn with additional of another molecule)

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

phase II reaction drug or metabolite is rendered more — and —

A
  • more polar

- less lipid soluble

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

phase II rxs with rare exception (eg. morphine), metabolites formed are

A

pharmacologically inactive

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

typical phase 1 reactions uses what 3 types of runs

A
  1. oxiations
  2. hydrolysis
  3. reductions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

example of oxidations of typical phase 1 rxns

A
  • cytochrome P450-linked (mainly in liver)
  • epoxide hydrolase
  • alcohol, aldehyde dehydrogenase
  • xanthine oxidase (purines)
  • monoamine oxidase (amines; mitochondria)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

example of hydrolysis

A

ester and amide

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

examples of reductions

A

azo and nitro

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

what is cytochrome P-450

A
  • mediates oxidation rxns (mixed-function oxidase)
  • ancient “superfamily” with extensive phlyogenetic distribution
  • 18 gene families in humans, encoding > 50 enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CYP is an abbreviation for

A

cytochrome P450

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

CYP3 designates

A

family (>40% sequence homology)

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

CYP A designates

A

sub-family (>55% sequence homology)

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

CYP4 designates

A

specific gene/enzyme

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

CYP rxns are characterized as

A
  • a mixed-function-oxidase, dependent on NADPH and molecular O2
  • sort electron transport chain located in SER of liver and other organs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

various isoforms of cytochrome P450 catalyze what

A

the oxidation rxn with a low degree of substrate specificity

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

substrates of CYP rxns must be

A

lipid soluble

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

what factors influence drug metabolism

A
  • genetic P450 pattern/variant
  • exposure to inducers
  • up-regulation
  • inhibition of P450 isoforms
  • hepatic disease
  • age
  • sex
  • nutritional status/diet
  • adrenal and thyroid function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

genetic p450 pattern/variant alleles yields an average of

A

6 to 30 fold variation in the average rate of drug metabolism
-individual differences for certain isoforms subject to pharmacogenetic variation can be even more striking

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

how can exposure to inducers (drug/ environment) influence drug metabolism

A

-content of many CYPs can be increased by exposure to certain drugs and exogenous compounds (2x-3x)

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

up-regulation usually occurs by

A

enhanced gene transcription following prolonged exposure to inducer

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

consequences of influencing drug metabolism

A
  • increased rate of metabolism
  • enhanced first-pass effect
  • reduced bioavailability
  • decreased [plasma]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

inhibition of P450 isoforms may be due to

Study These Flashcards
A

competition for enzyme active site, inactivation, or interactions with the heme group

25
consequences of inhibiting P450 isoforms
- increase [plasma] of the parent drug - reduction in metabolite - exaggerated and prolonged pharmacological effects - increased likelihood of drug toxicity
26
what CYP enzymes are responsible for metabolizing most clinically important drugs
CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4,5
27
what CYP enzymes are primarily involved in drug metabolism
CYP1,2,3
28
drug metabolism represents
a potential source of significant drug interactions -there are large individual differences in the average rate of drug metabolism due to genetic and environmental influences
29
what are 3 biliary-fecal routes
1. transport systems 2. biliary secretion 3. enterohepatic cycle
30
where are biliary fecal-route transport systems located
in the heptocyte
31
function of biliary fecal route transport systems
actively uptake and secrete drugs and metabolites into the bile
32
what are biliary secretions
amphipathic, lipid-soluble conjugated metabolites with a MW of >300 may be secreted (MPR2) by the liver into the bile
33
enterohepatic cycle
active drug of its metabolite can be excreted in the feces or reabsorbed
34
glucuronide conjugates can be secreted and recovered to
the free,a chive drug in the intestinal lumen by bacterial enzymes
35
what is the formula for hepatic clearance
Cl organ= Q [CA-CV] = Q x E ``` Q= flow CA= [arterial] CV = [venous] ```
36
(CA-CV/CA) can be referred to as
the extraction ration of the drug (E)
37
what is intrinsic clearance
the intrinsic ability of the liver to eliminate a drug in the absence limitations imposed by blood flow
38
intrinsic clearance is a measure of
the Michaelis-Menten kinetic parameters for the eliminating process (ie. Vmax/Km)
39
high intrinsic clearance is relative to
blood flow
40
high intrinsic clearance is approximated and determined by
hepatic blood flow
41
how will decrease in blood flow affect high intrinsic clearance
will decrease Cl | decrease in blood flow due to aging, disease
42
will changes in plasma protein binding or enzyme activity affect high intrinsic clearance
will have minimal effect
43
low intrinsic clearance is relative to what
blood flow
44
low intrinsic clearance will be proportion to what
the unbound fraction of the drug in blood and the intrinsic clearance (ie. enzyme activity/biliary ecretion)
45
will changes in blood flow affect low intrinsic clearance
not significant effect on clearance
46
what will impact low intrinsic clearance
enzyme induction or changes in protein binding
47
what is the first-pass effect
orally administered drugs must pass through the liver before gaining access to the systemic circulation
48
what drugs will demonstrate reduced or low bioavailability
- drugs with high hepatic extractions | - drugs which are metabolized rapidly compared with their rate of absorption
49
what are the renal excretion methods
1. glomerular filtration 2. tubular secretion (active transport) 3. tubular reabsorption
50
glomerular filtration clears
unbound drug
51
tubular secretion (active transport) occurs where
proximal tubule; energy dependent
52
when does tubular secretion (active transport occur)
as rate approaches renal blood flow?
53
tubular secretion (active transport) are unaffected by what
protein binding
54
tubular reabsorption
- concentration gradient - Kp - pKa - influence of urinary pH
55
Renal clearance formula (ml/min)
(UxV)/P U= concentration of drug in urine V=volume of urine excreted per minute P= concentration of drug in plasma
56
clearance value of a drug filtered and completely reabsorbed
Cl=0
57
clearance of a drug filtered and not reabsorbed
Cl~120ml/min
58
clearance of a drug filtered and (max) secreted
Cl~650ml/min

Pharmacology (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions