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Flashcards in p450 reactions Deck (62):
1

AUC and steady state concentrations are dependent only on what

the enzymes involved

2

phases of liver metabolism

-phase 0 - uptake to hepatocyte
-phase 1 - oxidation, reduction, hydrolysis
-phase 2 - glucuronidation, methylate, acetylate
-phase 3 - excrete into blood

3

pharmacodynamics definition

what drugs do to the body

4

metabolism phase 1 reactions

oxidation
reduction
hydrolysis

5

metabolism phase 2 reactions

glucuronide conjugation
methylation
acetylation

6

metabolic processes affected my gene mutations

metabolism
transport
PD

7

5 functions of P450's

-metabolize drugs
-synthesize steroid hormones/bile acid
-synthesize prostaglandin, thromboxane, leukotriene
-metabolize fat-soluble vitamins
-synthesize vitamin D3

8

where are P450s

-ER of cells
-mainly in liver
-gut, lung, skin, kidney

9

most common P450s

1A2
2C9/2C19
2D6
2E1
3A4

10

solute carrier transporters typically go which direction

extracellular to intra (influx transport)

11

ATP binding cassette transporters go which direction

efflux

12

example of ATP binding cassette transporter

P-glycoprotein

13

P-glycoprotein drug importance when deficient

-tumor drug resistance
-reduction DOAC effect

14

power source of P-gp

ATP

15

reversible inhibition

temporary association with CYP

16

irreversible inhibition

suicide substrate that covalently binds to enzyme

17

types of reversible inhibition

competitive
noncompetitive
uncompetitive

18

noncompetitive inhibition

binds to a non-active site, making enzyme not function

19

uncompetitive inhibition

binds to enzyme-substrate complex

20

degree of inhibition depends on

affinity to enzyme

21

strong inhibitor classification

>5 fold increase in plasma AUC or >80% reduction in clearance

22

moderate inhibitor classification

>2 fold increase in plasma AUC or 50-80% reduction in clearance

23

weak inhibitor classification

>1.25 and <2 fold increase in plasma AUC or 20-50% reduction in clearance

24

when does inhibition occur

-within 24 hours
-can be concentration-dependent
-clinical effect may take a couple days

25

inducers function

-form more CYP enzymes or transporters via transcription

26

rifampin induces

2C9
2C19
3A4
P-gp
OATP

27

ritonavir induces

3A4
P-gp
OATP

28

how long to see induction effects

3-5 days

29

things that cause autoinduction

carbamazepine
smoke
alcohol

30

strong inducer classification

>80 decrease in AUC

31

moderate inducer classification

50-80% decrease in AUC

32

weak inducer classification

20-50% decrease in AUC

33

examples of prodrugs

cyclophosphamide
codeine
hydrocodone

34

1A2 substrates

caffeine
clozapine
duloxetine
naproxen
theophylline
cyclobenzaprine

35

1A2 inhibitors

cimetidine
ciprofloxacin
fluvoxamine
amiodarone

36

1A2 inducers

charbroil
tobacco
rifampin

37

2C9 substrates

NSAIDS
fluoxetine
losartan
glipizide
phenytoin
warfarin

38

2C9 inhibitors

amiodarone
fluconazole (Strong)
isoniazide
metronidazole
paroxetine
Sulfamethoxazole
voriconazole

39

2C9 inducers

barbiturates
rifampin
SJW

40

2C19 substrates

amitriptyline
cyclophosphamide
clopidogrel
diazepam
lansoprazole
omeprazole
phenytoin

41

2C19 inhibitors

cimetidine
ketoconazole
fluoxetine
fluvoxamine
lansoprazole
omeprazole

42

2C19 inducers

efavirenz
rifampin
ritonavir
SJW

43

2D6 substrates

SGA's
codein
duloxetine
metoprolol
paroxetine
tramadol
tamoxifen

44

2D6 inhibitors

bupropion (S)
cimetidine
duloxetine
fluoxetine (S)
paroxetine (S)
quinidine (S)
ritonavir (S)
methadone

45

2D6 inducers

none, its resistant

46

2E1 substrates

APAP
acute alcohol

47

2E1 inhibitors

disulfiram

48

2E1 inducers

chronical alcohol

49

3A4 substrates

macrolides
benzos
immune modulators
HIV protease inhibs
CCB
statins
DOACs
methadone

50

3A4 inhibitors

amiodarone
nefazodone (S)
CCBs
grapefruit
ketoconazole (S)
clarithromycin (S)
erythromycin
cimetidine

51

3A4 inducers

carbamazepine
phenobarbital
phenytoin
rifabutin
rifampin
SJW

52

P-gp substrates

apixaban
rivaroxaban
dabigatran
digoxin
losartan

53

P-gp inhibitors

amiodarone
diltiazem
carvedilol
verapamil

54

P-gp inducer

amiodarone

55

fluoxetine primarily inhibits

2C19
2D6

56

fluvoxamine inhibits

1A2
2C19
2D6
3A4

57

paroxetine primarily inhibits

2D6
3A4

58

citalopram inhibits

barely any, very little DDI

59

2 herbal interactions to know about

SJW induce 3A4
Dill may inhibit 3A4

60

high risk drug interactions

-narrow therapeutic window drugs
-no alternate elimination pathways
-no alternatives
-dose adjustments not known

61

top 4 drug interactions to be aware of

-sildenafil + isosorbide mononitrate (nitrate)
-potassium and spironolactone
-warfarin and basically anything
-tyrosine kinase inhibs + 3A4 inhib/QT drugs/P-gp inhib/PPIs

62

rate of DDIs increase with

-# of prescribed meds
-# of OTC meds
-increased age age