Drug interactions Flashcards
refers to the effect or change that a drug has on the body
pharmacodynamics
what kind of interaction occurs when two or more drugs are given together?
PD drug interaction
Additive vs synergism?
additive = drugs that have similar end effects through different mechanisms/receptors
synergism = effect from two drugs taken in combo is greater than the effect from simply adding the two individual effect together
drugs with polyvalent cations or other binding properties should be separated from what drugs?
quinolones
tetracyclines
levothyroxine
oral bisphosphonates
What drugs require an acidic pH environment (ie interaction with PPIs)
antifungals
The majority of PK drug interactions occur where?
during metabolism in the liver
Who should not use codeine?
Ultra rapid metabolizers of 2D6 due to toxic levels of morphine
inhibitors or inducers?
decrease enzyme function and the ability to metabolize compounds
inhibitors
drugs that are substrates for the same CYP enzyme will have a/n inc/dec rate of drug metabolism and a/n increased/decreased serum drug level
dec metabolism
inc drug level
with prodrugs, the opposite happens with in inhibitor… what happens?
the active drug concentration decreases with an inhibitor (needs to be converted to active form by metabolism!)
What are major CYP inhibitors?
G PACMAN
G- grapefruit
P- protease inhibitors (esp ritonavir)
A- azole antifungals (fluconazole, itraconazole, keto, posa, vori, isavuconazonium)
C- cyclosporin, cimetidine, cobistat
M- macrlides (clarithromycin, erythromycin, but NOT azithromycin)
A- amiodarone (and dronedarone)
N- non-DHP CCBs (diltiazem and verapamil)
What effect do major CYP inhibitors have on substrates?
deceased metabolism = increased serum concentrations
INhibitors= INcreased effects
CYP inhibitors effect on prodrugs
decreased conversion to active drug, dec levels
What is the effect of inducers?
increase enzyme production/activity
what is the effect of inducers on substrates?
drugs that are substrates for the same CYP will have an increased rate of drug metabolism and a decreased serum drug level
More or less drug lost with inhibitors in first pass?
less
More or less drug lost with inducers in first pass?
more
what is the effect of an inducer on a prodrug?
increases effect!
what are the major CYP inducers?
PS CORPS
Phenytoin
St. John’s Wort
Carbamazepine (also an auto-inducer)
Oxcarbazempine (and eslicarbazepine)
Rifampin (and rifabutin, rifapentine)
Phenobarbital
Smoking
What effect do inducers have on substrates?
increased metabolism
decreased serum concentrations and decreased effect
inDucers = Decreased effects
Inhibitors vs inducers… time for enzyme action?
inhibitors = FAST!!!
inducers = “lag” time –> full effect on drug levels may not be seen for up to 4 weeks, when inducer is stopped could take 2-4 weeks for induction effects to disappear completely
when a drug inhibits Pgp pump, a drug that is a Pgp substrate will have inc/dec absorption
inc or dec level of drug?
increased absorption, substrate drug level will increase
What are some common Pgp substrates?
CHICA
Anticoagulants (apixaban, ribaroxaban)
Cardiovasular drugs (digoxin, diltiazem, verapamil)
Immunosuppressants (cyclosporin, tacrolimus)
HCV drugs (ombitasvir, paritaprevir, dasabuvir)
Colchicine
Pgp inducers?
PS CPR
phenytoin
st johns wort
carbamazepine
phenobarbital
rifampin
Pgp inhibitors?
CVAD
amiodarone,
diltiazem
verapamil)
cyclosporin
enterohepatic recycling inc or dec duration of action?
increases
describe enterohepatic recycling locations
metabolized in liver
transports back through the bile back to the gut
from the gut, reabsorbed in small intestine
enter portal vein
travel back to liver
What is the effect of amiodarone + warfarin?
INC WARFARIN LEVELS = DEC WARFARIN DOSE by 30-50%
amiodarone inhibits 2C9, which metabolizes warfarin
dec warfarin metabolism = inc INR = inc bleeding
what is the effect of amiodarone + digoxin?
DEC DIGOXIN DOSE BY 50%
amiodarone inhibits Pgp; digoxin is a substrate of Pgp
dec digoxin excretion = inc toxicity… risk of bradycardia
What is the effect of digoxin + loop?
DIGOXIN TOXICITY
loops decrease K, Mg, Ca, Na
Low K, Mg or Ca will worsen arrhythmias
What are drugs that decrease heart rate and have additive effects?
amiodarone
digoxin
BB
clonidine
What is the effect of statins + strong CYP3A4 inhibitors
GPACMAN
INC levels of Cyp3a4 substrates: lovastatin, simvastatin, atorvastatin
simva and lova are contraindicated
What is the effect of warfarin + 2C9 inhibitors & inducers?
inhibitors = INC levels of warfarin = INC INR
inducers = dec levels of warfarin = dec INR
What are some 2c9 inhibitors?
BAMA increases warfarin
azoles, Bactrim, amiodarone, metronidazole
what are some 2c9 inducers?
decrease warfarin
rifampin, st johns wort
What is the effect of 3a4 inhibitors + 3a4 substrates?
decrease 3a4 metabolism = inc drug levels = inc toxicity
*do NOT use a 3a4 inhibitor with an opioid metabolized by 3a4
grapefruit = do not use with 3a4 substrates
What drugs cannot be taken with grapefruit?
SLANT
amiodarone, simvastatin, lovastatin, nefidipine, tacrolimus
what opioids are 3a4 substrates?
fentanyl
hydrocodone
oxycodone
methadone
what is the effect of valproate + lamotrigine?
INC LEVELS OF LAMOTRAGINE (skin reactions!!)
valproate decreases lamotrigine metabolism
blocking MAO will inc or dec epi, NE, DA, and 5Ht?
increase! (epi, NE, DA hypertensive crisis) 5ht= SS
reason for washout period; fluoxetine - 5 weeks
What are drugs that will increase serotonin?
SSRis, SNRIs, TCAs, MAOi, mirtazapine, trazodone,
fentanyl, methadone, tramadol
buspirone, delsym, LITHIUM, st johns wort
triptans
linezolid
MAO inhibitors + tyramine rich foods will cause?
hypertensive crisis
do not eat aged cheese, air dried meats, sauerkraut
2d6 inhibitors + 2d6 substrates?
dec drug metabolism = toxicity
avoid use or dec dose of substrate
examples of 2d6 inhibitors?
F FAP
amiodarone
fluoxetine
paroxetine
fluvoxamine
3a4 or Pgp inhibitors
+
calcineurin inhibitors (tacrolimus, cyclosporine)
or
mTOR kinase inhibitors (sirolimus, everolimus)
decrease drug metabolism = inc toxicity
avoid use together or decrease dose of CNI, mTOR
what is a common drug that can decrease drug levels of phenytoin, phenobarbital, primidone, carbamazepine/oxcarbamazpine
oral contraceptives… loss of seizure control
smoking (inducer 1a2) +
some antipsychotics, antidepressants, hypnotics, anxiolytics, caffeine, theophylline, warfarin (r-isomer)
smokers who quit: drug concentrations will increase
current smoker: decrease levels
Bleeding risk drugs?
anticoagulants
antiplatelets
NSAIDs
SSRi, SNRIs
garlic, ginger, ginkgo, ginseng, glucosamine
Vitamin E
willow bark
fish oils (high mg)
what can cause high K?
spironolactone, eplerenone - highest risk
ACE, ARBs, entresto
amiloride, triamterene, KCl, tacrolimus, cyclosporin, canagliflozin, bactrim, drospirenone OC
QT prolongation drugs?
amiodarone (DOC in arrhythmia for HF), dofetlide, sotalol,
quinolones/macrolides
azoles
TCAs, SSRI (escitalopram 20/10mg and citalopram 40/20mg)>, mirtazapine, trazodone, SNRI
haloperidol, ziprasodone
antiemetics
donepezil, fingolamid, methadone
What drugs cause ototoxicity?
AG
cisplatin
loops
salicylates
vancomycin
what drugs cause nephrotoxicity?
AG, ampho B, polymyxins, vancomycin
cisplatin (use amifostine to protect kidneys)
cyclosporine, tacrolimus
loops
NSAIDs
radiographic contrast dye
PDE-5 inhibitors should start with a lower dose when used in combo with either of these 3 drug classes
3a4 inhibitors
nitrates
alpha-1 blockers
what drugs can cause anticholinergic toxicity?
paroxetine, TCA, FGA
sedating antihistamines
atropine, dicyclomine, meclisine
benztropine
baclofen, carisodolol, cyclobenzaprine
oxybutinin, tolterodine
fentanyl, hydrocodone, methadone, oxycodone
apixaban, rivaroxaban, R-warfarin
amlodipine
cycloposporin, tacrolimus, sirolimus
atorvastatin, lovastatin, simvastatin
avanafil, sildenafil, tadalafil, vardenafil
ethinyl estradiol
what cyp?
3a4 substrate
carbamazpine, oxcarbamazpine, phenobarbitol, phenytoin, rifampin, smoking, st John wort
3a4 inducers
clarithromycin, erythromycin, azoles
amiodarone, diltiazem, verapamil
cobicstat, protease inhibitors, ritonavir
cyclosporine, grapefruit
3a4 inhibitors
