Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
81 Cards in this Set
- Front
- Back
|
drug interactions can occur thru changes in
|
Pharmacokinetics: absorption, distribution, metabolism, elimination
pharmcodynamics: enhanced or diminshed effect or both |
|
|
many interactions mediated thru
|
cytochrome P enzyme system
|
|
|
what's the direction:
take two meds and one is affected |
unidirectional
|
|
|
what's the direction:
take two meds and they affect each other |
bidirectional
|
|
|
this is affected by the interaction
|
object drug
|
|
|
this drug causes the interaction
|
precipitant drug
|
|
|
how can absorption be altered to cause drug interactions
|
complexation/chelation/binding
altered GI transit altered gastric pH |
|
|
ex of complexation/chelation/binding:
|
antacids and fluoroquinolones
statins and cholestryamine |
|
|
fluroquinolones complex w/ --- ---- forming an insoluable complex
|
divalent cations
|
|
|
the insoluable complex stay in the intestine and decrease -----
|
bioavailability
|
|
|
what can decrease the statin bioavailability
|
cholestyramine
|
|
|
ex of altered gastric emptying/gi transit
|
anticholinergics and acetaminophen
|
|
|
what can increase motility
|
metoclopramide
erythromycin |
|
|
what can decrease motility
|
narcotics
anticholinergics |
|
|
t/f
altered gastric emptying/gi transit affects extent of absorption not rate |
f
affects rate not absorption |
|
|
due to decreased motility by anticholinergics what occurs w/ acetaminophen
|
delay in absorption of acetaminophen
|
|
|
w/ sumatriptan what can occur to the cmax of apap
|
decrease in cmax
so tmax delayed delayed onset due to change in gastric motility |
|
|
ex of altered gastric pH
|
H2 blockers and ketoconazole
|
|
|
w/ H2 blockers what occurs w/ ketoconazole
|
decreased dissolution, so decreased absorption
not soluable at neutral pH change in absorbtion |
|
|
which will decrease absorption more:
keto w/ sucrafate or keto w/ ranitidine |
keto w/ ranitidine
|
|
|
t/f
changes in protein binding is clinically relelvant |
f
not clinically relevant |
|
|
name the phase:
functionalization transport conjugation |
phase 1: functionalization
2: conjugation 3. transport |
|
|
oxidation and reduction occur in which phase
|
1
|
|
|
biliary and renal occurs in which phase
|
3
|
|
|
gluronidation and sulfation occurs in which phase
|
2
|
|
|
cyp P450 and flavin-monooxygenases occur in which phase
|
1
|
|
|
ugt and st phase
|
2
|
|
|
abc
mdr phase |
3
|
|
|
t/f
in order to get to phase 3 you need to get thru 1 |
f
no need to go thru phase 1 |
|
|
metabolism occurs in all phases
|
f
in 3 there's only transport |
|
|
predominant route of eliminations
|
metabolic: 68%
renal: 28% biliary: 4% |
|
|
what;s the predominant metabolic pathway
|
1. cypP450
2. non cyp ox/red 3. conjugation 4. hydrolysis |
|
|
cyp2D6
what's the family? subfamily? individual enzyme? |
family: 2
subfamily: D individual enzyme: 6 |
|
|
most drug interaction occur w/ these cyp's
|
1. CYP3A (52%)
2. CYP2D6 (25%) 3. CYP2C9/2C19 (18%) |
|
|
meds affected by cyp3A
|
cyclosporine
ccb's midazolam ritonavir statins |
|
|
meds affected by cyp2D6
|
antidepressants
bb ssri's |
|
|
meds affected by cyp2C9/2C19
|
losartan
nsaids ppi's phenytoin warfarin |
|
|
drugs an be -----, inhibitors, and or -----
|
substrates
inducers |
|
|
a med that can a substrated, inhibitor, and an inducer
|
ritonavir
CYP3A4: substrate altered by rifampin (enzyme inducer) CYP3A4 inhibitor: increases saquinavir CYP1A2: inducer: decreases theophylline conc |
|
|
cyp enzyme inducers
|
rifampin
rifabutin carbamezepine phenobarbital st. john's wort |
|
|
smoking indues CYP----
|
CYP1A2
|
|
|
one substrate competing w/ another for metabolism by a CYP
|
competitive
|
|
|
noncompetitive inhibition: an inhibitor tightly or ----- binds to the cyp enzyme, inhibiting it's activity
|
irreversibly
|
|
|
t/f
w/ cyp enzyme inhibition there'l be decrecred effect from the drug and increased effect from the metabolite |
f
increased effect from the drug and decrease effect from the metabolite |
|
|
which will have a lag time: induction or inhibition
|
induction
|
|
|
grapefruit juice is an inhibitor/inducer
|
inhibitor
|
|
|
t/f
w/ gfj there will be increase in t1/2 |
f
no change in t1/2 cuz no effects on liver |
|
|
gfj will increase -----
|
bioavailability
cmax auc |
|
|
where does gfj impact
|
enterocyte
|
|
|
what enzyme does gfj inhibit
|
CYP3A
|
|
|
what effect does gfj have on p glycoprotein
|
none
|
|
|
gfj reduces ---/parent drug auc ration
|
metabolite
|
|
|
gfj causes a 62% reduction in small bowel enterocyte cyp----- protein
|
cyp3A4/5
|
|
|
how long can gfj effects last
|
about 2 days
|
|
|
effects of gfj highly -----
|
variable
depends on individual |
|
|
when is the effect of gfj significant
|
pt takes higher than norm dose of med and drinks gfj for the 1st time
pt has severe liver disease pt has an unusual susceptibility to an ae (drug has to be metabolized by both intestine and cyp3A4) |
|
|
inhibitors of CYP3A4
|
GFJ
ketoconazole |
|
|
inducers of CYP3A4
|
rifampin
|
|
|
inhibitors of cyp2D6
|
paroxetine
|
|
|
inducer of CYP2C9
|
rifampin
|
|
|
inhibitor of cyp2C9
|
fluconazole
|
|
|
inducer of cyp1A2
|
rifampin
|
|
|
inhibitor of cyp1A2
|
fluvoxamine
|
|
|
cyp2c19 inducer
|
rifampin
|
|
|
cyp2c19 inhibitor
|
ticlopidine
|
|
|
what's measured in plasma w/ st john's wort
|
hypericin
hyperforin |
|
|
there's drug interactions w/ hyperforin and the ---- ligand cyp3A4
|
PXR
|
|
|
st. john's is an inducer of
|
cyp3a
|
|
|
st john's can affect these drugs
|
alprazolam
amitriptyline cyclosporine dig midazolam oral contraceptives nifedipine simvastatin tacrolimus |
|
|
st. john's has the greatest effects on cyp3a metabolized drugs that undergo ---- metabolism
|
first pass (intestinal)
cyp3A mainly found in intestine |
|
|
which will be more affected by st. john's wort
midazolam or alprazolam |
midazolam
(alprazolam not extensively metabolized in intestine) |
|
|
st john's have no effect on:
|
caffeine
carbamazepine dextromethorphan mycophenolic acid pravastatin |
|
|
echinacea is an inhibitor of
an inducer of ----- |
cyp3A
inhibitor of intestine inducer of hepatic met |
|
|
st john's inducer of cyp ----
|
CYP2C9
CYP3A |
|
|
gingko biloba is an inhibitor of
|
CYP2C19
|
|
|
term: intentionally given to boost another med
|
pharmacoenhancement:
antiHTN combo antiretroviral |
|
|
what inhibitor can be given for PK boosting for antiretrovirals
|
ritonavir
increase bioavailability of protease inhibitors decrease dose and frequency |
|
|
w/ both p glycoproteins and cpy 3a how are there more chances to be metabolized
|
most drugs are first pumped by p glyco then to cyp3a for metab.
|
|
|
what's the commonly used substrated to study p glyco
|
dig
|
|
|
what can be given w/ amoxicillin to increase it's auc and t1/2
|
probenecid
|
|
|
there are interactions that occur at the receptors or site of action level. there is ---- achange in the conc-effect profile
|
always
|
