Learning Drug Interactions

Question 1

Amiodarone + Warfarin

Answer 1

Ami = CYP2C9 inhibitor, Warfarin = CYP2C9 substrate –> increase warfarin concentration = increase in INR

• If adding ami after warfarin already being used, decrease warfarin dose by 30-50%
• If adding warfarin after ami already bring used, start warfarin at a lower dose
• If patient already using both, monitor INR and adjust as needed

Question 2

Amiodarone + Digoxin

Answer 2

Ami inhibits P-gp, digoxin is substrate. = digoxin ADRs and toxicity.

Both also reduce HR, so risk of bradycardia.

• If adding ami after existing digoxin, reduce PO digoxin dose by 50%
• If adding dig after existing ami, start dig at lower dose
• If taking both: tell pt to monitor for dig tox, brady (HR), check for other drugs that lower BP like beta blockers, clonidine, diltiazem, verapamil.

Question 3

Digoxin + Loop Diuretics

Answer 3

Loops DECREASE K Mg Ca and Na; Dig tox risk is increased with low K and Mg levels and increased Ca levels; monitor electrolytes

Question 4

Drugs that DECREASE HR

Answer 4

Ami
Beta blockers
Dig
Clonidine

Question 5

Statins + Strong CYP3A4 Inhibitors

Answer 5

= increased levels of CYP3A4 substrates ALS atorva, lova, simva

= increased myopathy and/or rhabdo risk

Simva and lova are CI-ed –> rec a non-CYP3A4 substrate statin like pita, prava, rosuva

Question 6

Warfarin + CYP2C9 inhibitors and inducers

Answer 6

inhibitors increase warfarin conc; increased INR and bleeding risk

inducers decrease warfarin conc; decrease INR and increased risk of clotting

Question 7

Valproate + Lamotrigine

Answer 7

Valproate is an inhibitor of lamotrigine metabolism; using together can cause increase lamotrigine concentration; main concern is increased risk for skin reactions, can combat with use of lamotrigine starter kit

Question 8

MAOI’s

Answer 8

isocarboxazid, phenelzine, tranylcypromine, linezolid, methylene blue

Question 9

MAO-I +

Drugs that INCREASE Epi, NE, DA +

Drugs that INCREASE Serotonin

Answer 9

MAO enzyme metabolizes E, NE, DA.

MAO inhibitor + drugs that increase E, NE, DA = increase in E, NE, or DA = hypertensive crisis

MAO inhibitors + drugs that increase serotonin = serotonin syndrome; do not combine these drugs. use a 2 week washout between serotonergic drugs and other antidepressant; if using fluoxetine and switching to MAO-inhibitor, a five week washout period is needed.

Question 10

Drugs that INCREASE Epi, NE, DA

Answer 10

Epi, NE, PSE, phenylephrine, dobutamine, SNRIs, bupropion, stimulants like amphetamines for ADHD [ex; methylphenidate, lisdexamphetamine, dextroamphetamine]

Question 11

Drugs that INCREASE Serotonin

Answer 11

Antidepressants, opioids, others

Antidepressants: SSRIs, SNRIs, TCAs, MAO inhibitors, mirtazapine, trazodone

Opioids: fentanyl, methadone, tramadol

Others: buspirone, dextromethorphan, lithium, St. John’s Wort

Question 12

MAO-I + tyramine-rich foods/drinks

Answer 12

Tyramine increases NE.

MAO metabolizes tyramine.

Eating tyramine rich foods while on a MAO inhibitor can increase tyramine concentration, leading to increase NE, which can cause hypertensive crisis.

Question 13

Tyramine-rich foods/drinks

Answer 13

Aged, pickled, fermented or smoked; including aged cheese, air-dried meats, sauerkraut, some wines and beers.

Question 14

CYP2D6 INHIBITORS

Answer 14

Amiodarone, fluoxetine, paroxetine, fluvoxamine

Question 15

CYP2D6 substrates

Answer 15

many; avoid using together or decrease dose of the substrate

Question 16

CYP3A4, P-GP inhibitors +

calcineurin inhibitors (CNIs) OR

mTOR Kinase inhibitors

Answer 16

decrease in drug metabolism, increase in ADRs/toxicity; avoid using together and monitor drug levels, lower CNI or mTOR kinase drug dose

Question 17

Calcineurin inhibitors (CNIs)

Answer 17

tacrolimus, cyclosporine

Question 18

mTOR Kinase inhibitors

Answer 18

sirolimus, everolimus

Question 19

Phenytoin, Phenobarbital, Primidone, Carbamazepine, Oxcarbazepine

+

Other drugs metabolized by CYP enzymes

Answer 19

reduced effect of drug, monitor drug levels, if substrate is lamotrigine and pt on CYP inducer, use the starter kit that has the higher dose.

Question 20

CYP3A4 inducers + opioids that are CYP3A4 substrates

Answer 20

analgesia reduced effect, avoid just increasing opioid dose, maybe another non-opioid for breakthrough pain control

Question 21

Opioids that are CYP3A4 substrates

Answer 21

fentanyl, hydrocodone, oxycodone, methadone

Question 22

CYP2D6 UMs + Prodrugs (ex: codeine, tramadol)

Answer 22

Rapid and more conversion of a prodrug to its active form; increase tox risk

Question 23

CYP3A4, P-GP inducers +

Calcineurin inhibitors (CNIs) OR

mTOR Kinase inhibitors

Answer 23

Decreased transplant drug level, increased risk of transplant rejection; avoid concurrent use but if needed, monitor transplant drug levels [trough] for efficacy

Question 24

Smoking + some antipsychotics, antidepressants, hypnotics, anxiolytics, caffeine, theophylline, R-isomer warfarin

Answer 24

current smoker; substrate levels will be sub-therapeutic, a higher dose may be required.

on a substrate and smoking but not quitting; substrate levels may increase and cause toxicity

Question 25

P-GP substrates

Answer 25

anticoagulants, CV drugs, immunosuppressants, HCV drugs, other

anticoags: apixaban, rivaroxaban

CV drugs: dig, diltiazem, verapamil

immunosuppressants: cyclosporine, tacrolimus

HCV drugs: ombitasvir, paritaprevir, dasabuvir

other: colchicine

Question 26

P-GP inducers

Answer 26

similar to CYP3A4 inducers; carbamazepine, rifampin, st johns wort, phenytoin, phenobarbital

Question 27

P-GP inhibitors

Answer 27

similar to CYP3A4 inhibitors

Question 28

CYP3A4 inhibitors

Answer 28

ami, azoles, dilt, verap, cyclosporine

Question 29

CYP3A4 inducers

Answer 29

PSPORCS

phenytoin, smoking, phenobarbital, oxcarbazepine, carbamazepine, rifampin, St. John’s Wort

Question 30

Warfarin is a substrate of which enzymes?

Answer 30

CYP2C9 (major), 1A2, 2C19, 3A4

Question 31

***Serotonergic toxicity - Drug combos causing additive side effects

Answer 31

antidepressants, MAO-I, buspirone [works on 5HT-1A], dextromethorphan, dihydroergotamine (migraine meds), lithium, lorcaSERin, opioids, metoclopramide, triptans, St. John’s Wort, I-tryptophan, tegaSERod

Question 32

***Bleeding risk - Drug combos causing additive side effects

Answer 32

anticoagulants, anti-platelets, NSAIDs, SSRIs and SNRIs***, natural products [5 G’s; ginger gingko garlic ginseng glucosamine, vitamin E, willow bark, high dose fish oils]

Question 33

***Hyperkalemia risk - Drug combos causing additive side effects

Answer 33

• highest risk - spironolactone, eplerenone,
• RAAS drugs - ACE, ARBs, aliskiren [Tekturna], sacubatril/valsartan [Entresto]
• amiloride, triamterene, salt substitutes (KCl), CNIs (tacrolimus, cyclosporine), canagliflozin, bactrim, drosperinone containing OCs

Question 34

***QT Prolongation - Drug combos causing additive side effects

Answer 34

anti-arrhythmatics, antibiotics/anti-fungals, antidepressants, most antipsychotics, antiemetics, others

anti-arrhythmatics-

antibiotics/anti-fungals- quinolones, macrolides, azoles [except isovocunazonium (Cresemba)]

antidepressants-

most antipsychotics-

antiemetics-

others- donepazil, fingolimod, methadone

Question 35

***CNS depression - Drug combos causing additive side effects

Answer 35

opioids, muscle relaxants, antiepileptics, BZDs, barbiturates, hypnotics, mirtazapine, trazodone, dronabinol [antiemetic, appetite stimulant], nabilone [Cesamet, man made form of cannabis], propanolol [Inderal], clonidine, sedating antihistamines, cough syrups with antihistamines or opioids, some NSAIDs, alcohol

ER form of opioids have an added risk with alcohol- ER forms when taken with alcohol can make the drug shorter acting, thus increasing the risk of fatality

Question 36

***Ototoxicity - Drug combos causing additive side effects

Answer 36

AGs, cisplatin, loop diuretics [especially IV], salicylates [ASA, salsalate, magnesium salicylate], vancomycin

Question 37

***Nephrotoxicity - Drug combos causing additive side effects

Answer 37

AGs, amphotericin B, polymyxins

Question 38

***Anticholinergic toxicity - Drug combos causing additive side effects

Answer 38

paroxetine, TCAs, 1st gen antipsychotics, sedating antihistamines [diphenhydramine, bropheniramine, chlorpheniramine, doxylamine, hydroxyzine, cyproheptadine], atropine, belldonna, dicyclomine, meclizine, benztropine, trihexyphenidyl, muscle relaxants [baclofen, carisprodol, cyclobenzaprine], overactive bladder antimuscarinics [oxybutynin, darifenacin, tolterodine]

Question 39

Hypotension/orthostasis - Drug combos causing additive side effects

Answer 39

PDE-5 inhibitors + CYP3A4 inhibitors OR Nitrates OR Alpha-1 blockers

Question 40

CYP1A2 substrates, inducers, inhibitors

Answer 40

• substrates: theophylline, R-warfarin
• inducers: carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort
• inhibitors: ciprofloxacin, fluvoxamine

Question 41

CYP2C9 substrates, inducers, inhibitors

Answer 41

• substrates: S-warfarin
• inducers: carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort
• inhibitors: ami, azoles, bactrim

Question 42

CYP2C19 substrates, inducers, inhibitors

Answer 42

• substrates: clopidogrel
• inducers: carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort
• inhibitors: esomeprazole, omeprazole

Question 43

CYP2D6 substrates, inducers, inhibitors

Answer 43

• substrates: codeine, meperidine, tramadol, antipsychotics/antidepressants, tamoxifen
• inducers: none [have UMs and PMs]
• inhibitors: