Drug Interactions

Question 1

What drugs are most commonly involved in DDIs?

Answer 1

nsaids, anticoagulants/antiplatelets, cardiovascular drugs

Question 2

What is a pharmacodynamic drug interaction?

Answer 2

one drug has a pharmacological action that increases or decreases/alters the action of another drug; Cannot be mediated by adjusting the dose of the interacting drugs

Question 3

What is a pharmacokinetic drug interaction?

Answer 3

one drug alters the concentration of another drug in the body through absorption, distribution, metabolism, or elimination
Can be remedied through dose adjusting

Question 4

What is a CYP450 inducer?

Answer 4

medications that increase the rate of metabolic activity

Question 5

What is a CYP450 inhibitor?

Answer 5

medications that decrease the rate of metabolic activity

Question 6

What is CYP450 substrate?

Answer 6

medications that use this pathway to be metabolized in the liver

Question 7

What is the role of P-glycoproteins?

Answer 7

transporters found in gut and other organs that pump drugs out of the bloodstream and into the gut (is the drug able to efflux or does it inhibit this transporter?)

Question 8

What are 2C9 inhibitors?

Answer 8

bactrim, metronidazole

Question 9

What are 2D6 inhibitors?

Answer 9

TCAs, fluoxetine, paroxetine

Question 10

What are 3A4 inhibitors?

Answer 10

haloperidol, azoles, protease inhibitors, NNRTIs, Diltiazem, verapamil, erythromycin (2-3 days)

Question 11

What are P450 inducers?

Answer 11

rifampin, carbamazepine, phenobarbital, phenytoin, ritonavir, efavirez, St John’s wort, nafcillin
(2-3 weeks)

Question 12

What’s a good mnemonic for inducers?

Answer 12

CORPPSES
carbamazepine
oxcarbazepine
rifampin
phenytoin
phenobarbital & primidone
smoking
efavirenz
st john’s

Question 13

What’s a good mnemonic for inhibitors?

Answer 13

GPACMAN
grapefruit
protease inhibitors
azole antifungals
cimetidine
macrolides (not azithromycin)
amiodarone
non-dihydropyridine calcium channel blockers (Diltiazem and verapamil)

Question 14

What is warned against regarding drug-disease interactions with chronic NSAID use?

Answer 14

chronic renal insufficiency, heart failure, previous peptic ulcer disease

Question 15

What should you not take with heart failure?

Answer 15

diltiazem or verapamil

Question 16

What should you not take with chronic renal insufficiency or heart failure?

Answer 16

metformin

Question 17

What should you be wary with regarding thiazide diuretics?

Answer 17

gout and renal status

Question 18

What are clinical presentations of drug interactions?

Answer 18

serious ADR, poor tolerability, decreased efficacy, worsening of state, withdrawal symptoms

Question 19

How are prodrugs affected by inhibition or induction of CYP450 enzymes?

Answer 19

inhibition = lower amount of active drug
induction = higher amount of active drug

Question 20

What does amiodarone do?

Answer 20

inhibitor of 2C9, 2D6, 3A4, which when paired with other drugs of those pathways, can lower metabolism, which increases their effect

Question 21

What should you lower the dose by 30-50% with amiodarone?

Answer 21

digoxin (risk of toxicity), warfarin (risk of bleeding)
and grapefruit

Question 22

What are examples of azole antifungals?

Answer 22

ketoconazole, itraconazole, voriconazole, posaconazole

Question 23

What do itraconazole and ketoconazole require?

Answer 23

low pH for effective absorption – avoid using with drugs that raise pH

Question 24

What drug interactions should you consider with voriconazole?

Answer 24

inhibitor of 2c9, 2c19, 3a4, MANY ddrugs are contraindicated in conjunction with voriconazole

Question 25

What is digoxin?

Answer 25

narrow therapeutic index medication, substrate of p-glycoprotein

Question 26

What is digoxin's relationship with serum potassium levels?

Answer 26

digoxin level and K level are inversely related -- more risk of toxicity w/ hypokalemia >4 K+ goal

Question 27

What is the effect of renal dysfunction on digoxin?

Answer 27

lower renal function = lower digoxin dose

Question 28

What are examples of statins?

Answer 28

lovastatin, simvastatin, atorvastatin

Question 29

What are statins?

Answer 29

substrates of 3a4 -- if you take this with a 3a4 inhibitor, it will be stuck in the blood, and are at risk for higher muscle toxicity/damage

Question 30

What statins can be a backup in regards to other pathways?

Answer 30

pravastatin or rosuvastatin

Question 31

What stems from drug interactions with lithium?

Answer 31

renal issues. You have to have good kidneys

Question 32

When will increased lithium levels maybe occur?

Answer 32

anti-inflam ACE-inhib ARBs dehydratioin diuretics

Question 33

What are some MAO inhibitors?

Answer 33

isocarboxazid, phenelzine, selegiline, tranylcypromine

Question 34

What do MAO-Is affect?

Answer 34

decreased metabolism of monoamines -- nore, epi, serotonin, tyramine (pickled, fermented, aged foods)

Question 35

What are ADRs that MAO-Is cause?

Answer 35

serotonin syndrome, HTN crisis, or even fatal with drugs that raise the level of monoamines --> antidepressants, triptans, dextromethorphan

Question 36

How do NSAIDs work?

Answer 36

inhibit the cox pathways, lower synthesis of prostaglandins

Question 37

What are risks of NSAID use?

Answer 37

increased risk of GI bleeding, kidney injury, cardio toxicity

Question 38

What can decrease the effectiveness of oral contraceptives?

Answer 38

CYP450 enzyme inducers -- anticonvulsants (barbiturates, phenytoin, carbamazepine), St. John's, some HIV drugs, smoking

Question 39

What is rifampin?

Answer 39

gold standard inducer of many pathways - 2c9, 2c19, 3a4 (NOT 2d6)

Question 40

What will rifampin do?

Answer 40

decrease concentration of any drug that is a substrate of many pathways; used to treat Tb and leprosy

Question 41

What is phenytoin?

Answer 41

inducer of 2c8, 9, 19, 3a4, and p-glycoprotein with highly protein albumin bound

Question 42

What does phenytoin do?

Answer 42

decreases the concentration of several drugs, can displace medications from albumin, *Caution with other CNS depressants due to additive effects*

Question 43

What is carbamazepine?

Answer 43

strong 3a4 inducer and induces its own metabolism -- decreases the level of MANY drugs that are 3a4 substrates

Question 44

So, what will 3a4 inhibitors or inducers do for carbamazepine?

Answer 44

inhibitors will increase levels (can induce its own metabolism) inducers will decrease levels

Question 45

What are tetracycline and quinolone antibiotics?

Answer 45

cipro, levo, moxi flox

Question 46

What decreases tetracycline and quinolone abx absorption?

Answer 46

multivitamins of aluminum, magnesium, calcium, iron, zinc --> separate administration time helps, includes dairy, antacids, sucralfate, aspirin

Question 47

How does warfarin work?

Answer 47

major 2c9 substrate, so induction of 2c9 will lower effectiveness, and inhibition will raise effectiveness

Question 48

When is there a bleeding risk for warfarin?

Answer 48

when combined with NSAIDs, antiplatelets, garlic, ginseng, ginkgo, foods high in vitamin K

Question 49

What are medications causing hyperkalemia?

Answer 49

ACE inhibitors ARB (angiotensin receptor blockers) potassium sparing diuretics trimethoprim aldosterone antagonists NSAIDs digoxin cyclosporine or tacrolimus

Question 50

What does hyperkalemia do?

Answer 50

cardiac arrhythmias and sudden cardiac death

Question 51

What can cause CNS depression?

Answer 51

alcohol, opiates, muscle relaxants, benzos, hypnotics, barbiturates

Question 52

What occurs when medication is combined and has addictive effects on a prolonged QTc interval?

Answer 52

lead to torsades de pointes (TdP) which could be from long intervals, bradycardia, electrolyte abnormalities, females, congenital

Question 53

What are red flag medications for QTc?

Answer 53

warfarin, HAART (highly active anti-retroviral therapy) amiodarone, antidepressants, quinolones, antipsychotics and abx, antiarrhythmics and abx, anti epileptic, statins