Drug Interactions Flashcards
What drugs are most commonly involved in DDIs?
nsaids, anticoagulants/antiplatelets, cardiovascular drugs
What is a pharmacodynamic drug interaction?
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
What is a pharmacokinetic drug interaction?
one drug alters the concentration of another drug in the body through absorption, distribution, metabolism, or elimination
Can be remedied through dose adjusting
What is a CYP450 inducer?
medications that increase the rate of metabolic activity
What is a CYP450 inhibitor?
medications that decrease the rate of metabolic activity
What is CYP450 substrate?
medications that use this pathway to be metabolized in the liver
What is the role of P-glycoproteins?
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?)
What are 2C9 inhibitors?
bactrim, metronidazole
What are 2D6 inhibitors?
TCAs, fluoxetine, paroxetine
What are 3A4 inhibitors?
haloperidol, azoles, protease inhibitors, NNRTIs, Diltiazem, verapamil, erythromycin (2-3 days)
What are P450 inducers?
rifampin, carbamazepine, phenobarbital, phenytoin, ritonavir, efavirez, St John’s wort, nafcillin
(2-3 weeks)
What’s a good mnemonic for inducers?
CORPPSES
carbamazepine
oxcarbazepine
rifampin
phenytoin
phenobarbital & primidone
smoking
efavirenz
st john’s
What’s a good mnemonic for inhibitors?
GPACMAN
grapefruit
protease inhibitors
azole antifungals
cimetidine
macrolides (not azithromycin)
amiodarone
non-dihydropyridine calcium channel blockers (Diltiazem and verapamil)
What is warned against regarding drug-disease interactions with chronic NSAID use?
chronic renal insufficiency, heart failure, previous peptic ulcer disease
What should you not take with heart failure?
diltiazem or verapamil
What should you not take with chronic renal insufficiency or heart failure?
metformin
What should you be wary with regarding thiazide diuretics?
gout and renal status
What are clinical presentations of drug interactions?
serious ADR, poor tolerability, decreased efficacy, worsening of state, withdrawal symptoms
How are prodrugs affected by inhibition or induction of CYP450 enzymes?
inhibition = lower amount of active drug
induction = higher amount of active drug
What does amiodarone do?
inhibitor of 2C9, 2D6, 3A4, which when paired with other drugs of those pathways, can lower metabolism, which increases their effect
What should you lower the dose by 30-50% with amiodarone?
digoxin (risk of toxicity), warfarin (risk of bleeding)
and grapefruit
What are examples of azole antifungals?
ketoconazole, itraconazole, voriconazole, posaconazole
What do itraconazole and ketoconazole require?
low pH for effective absorption – avoid using with drugs that raise pH
What drug interactions should you consider with voriconazole?
inhibitor of 2c9, 2c19, 3a4, MANY ddrugs are contraindicated in conjunction with voriconazole
What is digoxin?
narrow therapeutic index medication, substrate of p-glycoprotein
What is digoxin’s relationship with serum potassium levels?
digoxin level and K level are inversely related – more risk of toxicity w/ hypokalemia
>4 K+ goal
What is the effect of renal dysfunction on digoxin?
lower renal function = lower digoxin dose
What are examples of statins?
lovastatin, simvastatin, atorvastatin
What are statins?
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
What statins can be a backup in regards to other pathways?
pravastatin or rosuvastatin
What stems from drug interactions with lithium?
renal issues. You have to have good kidneys
When will increased lithium levels maybe occur?
anti-inflam
ACE-inhib
ARBs
dehydratioin
diuretics
What are some MAO inhibitors?
isocarboxazid, phenelzine, selegiline, tranylcypromine
What do MAO-Is affect?
decreased metabolism of monoamines – nore, epi, serotonin, tyramine (pickled, fermented, aged foods)
What are ADRs that MAO-Is cause?
serotonin syndrome, HTN crisis, or even fatal with drugs that raise the level of monoamines –> antidepressants, triptans, dextromethorphan
How do NSAIDs work?
inhibit the cox pathways, lower synthesis of prostaglandins
What are risks of NSAID use?
increased risk of GI bleeding, kidney injury, cardio toxicity
What can decrease the effectiveness of oral contraceptives?
CYP450 enzyme inducers – anticonvulsants (barbiturates, phenytoin, carbamazepine), St. John’s, some HIV drugs, smoking
What is rifampin?
gold standard inducer of many pathways - 2c9, 2c19, 3a4 (NOT 2d6)
What will rifampin do?
decrease concentration of any drug that is a substrate of many pathways; used to treat Tb and leprosy
What is phenytoin?
inducer of 2c8, 9, 19, 3a4, and p-glycoprotein with highly protein albumin bound
What does phenytoin do?
decreases the concentration of several drugs, can displace medications from albumin, Caution with other CNS depressants due to additive effects
What is carbamazepine?
strong 3a4 inducer and induces its own metabolism – decreases the level of MANY drugs that are 3a4 substrates
So, what will 3a4 inhibitors or inducers do for carbamazepine?
inhibitors will increase levels (can induce its own metabolism)
inducers will decrease levels
What are tetracycline and quinolone antibiotics?
cipro, levo, moxi flox
What decreases tetracycline and quinolone abx absorption?
multivitamins of aluminum, magnesium, calcium, iron, zinc –> separate administration time helps, includes dairy, antacids, sucralfate, aspirin
How does warfarin work?
major 2c9 substrate, so induction of 2c9 will lower effectiveness, and inhibition will raise effectiveness
When is there a bleeding risk for warfarin?
when combined with NSAIDs, antiplatelets, garlic, ginseng, ginkgo, foods high in vitamin K
What are medications causing hyperkalemia?
ACE inhibitors
ARB (angiotensin receptor blockers)
potassium sparing diuretics
trimethoprim
aldosterone antagonists
NSAIDs
digoxin
cyclosporine or tacrolimus
What does hyperkalemia do?
cardiac arrhythmias and sudden cardiac death
What can cause CNS depression?
alcohol, opiates, muscle relaxants, benzos, hypnotics, barbiturates
What occurs when medication is combined and has addictive effects on a prolonged QTc interval?
lead to torsades de pointes (TdP) which could be from long intervals, bradycardia, electrolyte abnormalities, females, congenital
What are red flag medications for QTc?
warfarin, HAART (highly active anti-retroviral therapy)
amiodarone, antidepressants, quinolones, antipsychotics and abx, antiarrhythmics and abx, anti epileptic, statins
