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Clinical Pharmacology > Drug Interactions > Flashcards

Drug Interactions Flashcards

1
Q

What drugs are most commonly involved in DDIs?

A

nsaids, anticoagulants/antiplatelets, cardiovascular drugs

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2
Q

What is a pharmacodynamic drug interaction?

A

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

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3
Q

What is a pharmacokinetic drug interaction?

A

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

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4
Q

What is a CYP450 inducer?

A

medications that increase the rate of metabolic activity

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5
Q

What is a CYP450 inhibitor?

A

medications that decrease the rate of metabolic activity

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6
Q

What is CYP450 substrate?

A

medications that use this pathway to be metabolized in the liver

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7
Q

What is the role of P-glycoproteins?

A

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?)

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8
Q

What are 2C9 inhibitors?

A

bactrim, metronidazole

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9
Q

What are 2D6 inhibitors?

A

TCAs, fluoxetine, paroxetine

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10
Q

What are 3A4 inhibitors?

A

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

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11
Q

What are P450 inducers?

A

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

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12
Q

What’s a good mnemonic for inducers?

A

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

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13
Q

What’s a good mnemonic for inhibitors?

A

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

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14
Q

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

A

chronic renal insufficiency, heart failure, previous peptic ulcer disease

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15
Q

What should you not take with heart failure?

A

diltiazem or verapamil

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16
Q

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

A

metformin

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17
Q

What should you be wary with regarding thiazide diuretics?

A

gout and renal status

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18
Q

What are clinical presentations of drug interactions?

A

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

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19
Q

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

A

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

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20
Q

What does amiodarone do?

A

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

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21
Q

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

A

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

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22
Q

What are examples of azole antifungals?

A

ketoconazole, itraconazole, voriconazole, posaconazole

23
Q

What do itraconazole and ketoconazole require?

A

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

24
Q

What drug interactions should you consider with voriconazole?

A

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

25
Q

What is digoxin?

A

narrow therapeutic index medication, substrate of p-glycoprotein

26
Q

What is digoxin’s relationship with serum potassium levels?

A

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

27
Q

What is the effect of renal dysfunction on digoxin?

A

lower renal function = lower digoxin dose

28
Q

What are examples of statins?

A

lovastatin, simvastatin, atorvastatin

29
Q

What are statins?

A

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

30
Q

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

A

pravastatin or rosuvastatin

31
Q

What stems from drug interactions with lithium?

A

renal issues. You have to have good kidneys

32
Q

When will increased lithium levels maybe occur?

A

anti-inflam
ACE-inhib
ARBs
dehydratioin
diuretics

33
Q

What are some MAO inhibitors?

A

isocarboxazid, phenelzine, selegiline, tranylcypromine

34
Q

What do MAO-Is affect?

A

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

35
Q

What are ADRs that MAO-Is cause?

A

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

36
Q

How do NSAIDs work?

A

inhibit the cox pathways, lower synthesis of prostaglandins

37
Q

What are risks of NSAID use?

A

increased risk of GI bleeding, kidney injury, cardio toxicity

38
Q

What can decrease the effectiveness of oral contraceptives?

A

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

39
Q

What is rifampin?

A

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

40
Q

What will rifampin do?

A

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

41
Q

What is phenytoin?

A

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

42
Q

What does phenytoin do?

A

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

43
Q

What is carbamazepine?

A

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

44
Q

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

A

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

45
Q

What are tetracycline and quinolone antibiotics?

A

cipro, levo, moxi flox

46
Q

What decreases tetracycline and quinolone abx absorption?

A

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

47
Q

How does warfarin work?

A

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

48
Q

When is there a bleeding risk for warfarin?

A

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

49
Q

What are medications causing hyperkalemia?

A

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

50
Q

What does hyperkalemia do?

A

cardiac arrhythmias and sudden cardiac death

51
Q

What can cause CNS depression?

A

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

52
Q

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

A

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

53
Q

What are red flag medications for QTc?

A

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

Clinical Pharmacology (14 decks)

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