DDI Flashcards
examples of prodrugs
codeine – morphine
clopidogrel
prednisone – prednisolone
tramadol
valacyclovir – acyclovir
levodopa – DA
cortisone – cortisol
prmodone – phenobarbital
codeine is activated by CYP____
2D6
hypermetabolizers of 2D6 will have ________ concentrations of morphine after taking codeine
slow metabolizers of 2D6 will have ______ concentrations of morphing after codeine admin
HMs will have higher morphine concentrations and increased risk of toxicity
slow metabolizers will have dec concentrations of morphine and have poor analgesic effects
clopidogrel is metabolized by CYP____
2C19
what is p-gp? what happens if it induced/inhibited)
p-gp effluxes drugs from the bloodstream back into the gut to be excreted in stool
inhibit pgp –> inc Cp of substrate
induce pgp –> dec Cp of substrate
common p-gp substrates
DOACs
dig, dilt, verapamil, cervedilol
cyclosporine and tacro
common p-gp inducers
carbamazepine
phenobarb
pnehytoin
rifampin
SJ Wort
common inhbitors of pgp
clarithro
itraconazole, posaconazole
amiodarone
dilt
verapamil
cobicistat, ritonavir
cyclosporine
what is enterohepatic recycling
drugs are metabolized in the liver then transported, through bile, back to the gut where drug can be reabsorbed, enter portal vein and go back to the liver
this increases duration of action of some drugs
what drugs undergo enterohepatic recycling
ABX
NSAIDs
zetia
amiodarone and warfarin DDI? How do we adjust dose(s)
w is a 2C9 substrate
a inhibits 2C9 causing inc Cp warfarin
if ADDING warfarin to a, start warfarin at low dose </= 5mg
if ADDING a to warfarin, dec warfarin dose 30-50%
monitor INR
amiodarone and digoxin DDI? How do we adjust dose(s)
amiodarone inhibits p-gp
dig is a p-gp substrate and amio will inc Cp when given together
if adding digoxin : start at 0.125mg daly
if adding amio: dec dig dose 50%
DDI between digoxin and loops
how to monitor
loops dec K, Na, Mg, Ca
digoxin toxicity is increased w/ dec K and Mg and inc Ca ESPECIALLY in renal imp
monitor electrolytes
statins and 3A4-i
lovastatin, simvastatin and atorvastatin are 3A4 substrates
3A4-i increase statin concentration and increase risk for rhabdo, AKI and myopathy
simva and lova are CI with strong 3A4-i
warfarin and 2C9 DDI
S-warfarin is metabolized by 2C9 and can be the cause of many DDI
which opioids are metabolized by 3A4?
fentanyl
oxycodone
hydrocodone
methadone
all CI with strong 3A4-i
VPA and lamictal DDI? How do we adjust dose(s)
VPA inhibits lamictal metabolism and increases Cp of lamictal which increases risk of toxicity including SJS/TEN
titrate lamictal very slowly
what does MAO metabolize
NE
DA
5-HT
tyramine
EN
inhibiting MAO will increase its substrates NE, EN, DA and tyramine leading to _____
hypertensive crisis
MAO-i examples
linezolid
selegeline
rasageline
methylene blue
isocarboxazid
tranylcypromine
MAO-is are of concern with which types of medications/substances
serotinergics
tyramine foods
sympathomimetics
what are the major 2D6 substrates
codeine
meperidine
tramadol
tamoxifen
how does rifampin usually contribute to DDI
strong p-gp and CYP inhibitor
how does smoking contribute to DI
induces 1A2 and 2C9
which drugs can contribute to serotonin toxicity
SSRI
SNRI
SRI
MAO-i
methadone, fentanyl, meperidine, tramadol
SJ wort
triptans
buspirone
lithium
linezolid
methylene blue
drugs that contribute to bleed risk
anticoags
NSAIDs
SSRI/SNRI
antiplatelets
teh 5G’s!
ginseng
ginger
ginko balboa
glucosamine
garlic
medications/conditions that contribute to hyperkalemia
KCl
RAAS-i
SMX/TMP
CN-i (tacro)
K-sparing diuretics (amiloride, triamterene, spironolactone)
canagliflozin
drosperinone in OCs
renal impairment!!!
medications that contribute to QT prolongation
5 A’s!
Antiarrhythmics
Anti-infectives: macrolides, FQs, azoles, antimalarials
ADs: trazodone, mirt, SSRI (escit, cit), venlafaxine, TCAs
APs: ziprasidone», 1st genes
Antiemetics: 5HT3 RAs, metoclopramide, promethazine, droperidol
others: loperamide, methadone
methadone places patients at risk of
serotonin syndrome and QT prolongation
CNS depressants
opioids
benzos
sk m relaxants
barbiturates
hypnotics
antihistamines
alcohol
cough syrups
cannabinoids (dronabinol)
mirtazepine
trazodone
ototoxins
vancomycin
AGs
cisplatin
loops
salicylates
nephrotoxins
NSAIDs
vanco
AGs
loops
radiographic contrast dye
Amph B
polymixins
CN-i (tacro, siro)
cisplatin
how do we prevent cisplatin-induced nephrotoxicity
use amifostine and fluids
orthostasis risk medications
PDE-5 -i
alpha blockers (flomax, doxazosin, terazosin)
nitrates
3A4 substrates
opioids fentanyl, oxycodone, hydrocodone, methadone, bup, tramadol
DOACs, warfarin
amiodarone, amlodipine, dilt, verap
atorv, simva, lova - statin
NNRTIs
PDE5-i
ethanyl estradiol
3A4 inducers
carbamazepine
phenobarbital
phenytoin
SJW
rifampin
3A4 inhibitors
clarithro, erythro
isoniazid
azoles
amodarone
diltiazem
verapamil
cobicistat
ritonavir
protease-i (-navir)
grapefruit
cyclosporine
CYP2C8 substrates
amiodarone
pioglitazone
repaglinide
CYP2C8 inducers
phenytoin
rifampin
CYP2C8 inhibitors
amiodarone
clopidogrel
ketoconazole
SMX/TMP
CYP2D6 substrates
codeine, meperidine, tramadol
APs
doxepin
trazodone
TCAs
ADs
tamoxifen
carvedilol
metoprolol
propranolol
CYP2D6 inducers
none
CYP2D6 inhibitors
amiodarone
duloxetine
fluoxetine
paroxetine
bupropion
cobicistat
CYP2C9 substrates
S-warfarin!!!!!
carvedilol
diazepam
SUs
phenytoin
tamoxifen
zolpidem
CYP2C9 inducers
smoking
carbamazepine
phenobarbital
phenytoin
rifampin
SJW
CYP2C9 inhibitors
amiodarone
fluuconazole
metronidazole
ketoconazole
voriconazole
VPA
TMP/SMX
tramadol therapy concerns
prodrug
2D6 and 3A4 substrate
serotinergic
trazodone therapy concerns
QTp
CNS depressant
2D6 substrate
azoles cause DDI by_________________
3A4 and 2C9 inhibition
CYP2C19 substrates
clopidogrel!!!
phenytoin
CYP2C19 inducers
phenobarbital
phenytoin
rifampin
carbamazepine
CYP2C19 inhibitors
esomeprazole
omeprazole
CYP1A2 substrates
R-warfarin
theophylline
some APs
hypnotics
anxiolytics
ADs
CYP1A2 inducers
smoking
phenobarbital
phenytoin
rifampin
carbamazepine
CYP1A2 inhibitors
fluvoxamine
ciprofloxacin
what are the common inducers and what CYPs do they induce
phenobarbital
phenytoin
rifampin
carbamazepine
3A4, 2C9, 2C19, 1A2
phenytoin and rifampin induce 2C8
