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
