Ch 3: Drug Interactions Flashcards

1
Q

Drugs w/ polyvalent cations or other binding properties

A

Antacids
Multivitamins
Sucralfate
Bild acid resins
Aluminum
Calcium
Iron
Magnesium
Zinc
Phosphate binders

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2
Q

Drugs w/ polyvalent cations or other binding properties should be separated from

A

Quinolones
Tetracyclines
Levothyroxine
Oral bisphosphonates

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3
Q

What are the major CYP3A4 inhibitors

A

Remember G <3 PACMAN

Grapefruit
<3
Protease inhibitors (PI), especially ritonavir (Norvir)
Azole antifungals (fluconazole, itraconazole, ketoconazole, posaconazole (Noxafil), voriconazole, and isavuconazonium (Cresemba))
Cyclosporine, cimetidine (Tagamet), cobicistat
Macrolides (clarithromycin (Biaxin) and erythromycin, but not azithromycin)
Amiodarone (and dronedarone (Multaq))
Non-DHP CCBs (diltiazem and verapamil)

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4
Q

Brand:Generic

Cardizem

A

diltiazem

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5
Q

Brand:Generic

Neoral

A

cyclosporine

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6
Q

What are the major CYP3A inducers

A

Remember SSR COPP

  • St. John’s Wort
  • Smoking
  • Rifampin (and rifabutin, rifapentine)
  • Carbamazepine (also an auto-inducer)
  • Oxcarbazepine (and eslicarbazepine)
  • Phenytoin
  • Phenobarbital
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7
Q

Brand:Generic

Dilantin

A

phenytoin

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8
Q

P-gp

Substrates

A

Anticoagulants (apixaban, edoxaban, dabigatran, rivaroxaban)

Cardiovascular drugs (digoxin, diltiazem, carvedilol, ranolazine, verapamil)

lmmunosuppressants (cyclosporine, sirolimus, tacrolimus)

HCV drugs (sofosbuvir)

Others (atazanavir, colchicine, dolutegravir, posaconazole, raltegravir, saxagliptin)

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9
Q

P-gp

Inducers

A

Carbamazepine,
dexamethasone,
phenobarbital,
phenytoin,
rifampin,
St. John’s wort,
tipranavir

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10
Q

P-gp

Inhibitors

A

Anti-infectives (clarithromycin, itraconazole, posaconazole)

Cardiovascular drugs (amiodarone, carvedilol, conivaptan, diltiazem, dronedarone, quinidine, verapamil)

HIV drugs (cobicistat, ritonavir)

HCV drugs (ledipasvir)

Others (cyclosporine, flibanserin, ticagrelor)

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11
Q

Enterohepatic recycling ↑ _

A

duration of action

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12
Q

Common Cardiovacular Drug Intxn

Amiodarone + Warfarin

A

If using warfarin 1st:
↓ warfarin dose 30-50%

Amiodarone inhibits CYP2C9, which metabolizes warfarin

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13
Q

Common Cardiovacular Drug Intxn

Amiodarone + Digoxin

A

If using digoxin 1st:
↓ digoxin dose 50%

Amiodarone inhibits P-gp, digoxin is a P-gp substrate → ↑ risk of bradycardia

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14
Q

Common Cardiovacular Drug Intxn: Digoxin + Loop Diuretics

What electrolytes do loops effect?

A

↓ K, Mg, Ca, & Na

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15
Q

Common Cardiovacular Drug Intxn: Digoxin + Loop Diuretics

What ↑ the risk of digoxin toxicity?

A

↓ K & Mg

↑ Ca

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16
Q

Common Cardiovacular Drug Intxn: Digoxin + Loop Diuretics

Drugs that ↓ HR

A

Amiodarone
Digoxin
BB
Clonidine
Diltiazem
Verapamil

Additive effects when use together. Monitor HR (normal: 60-100 BPM)

Also: dexmedetomide (Precedex)

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17
Q

Common Cardiovacular Drug Intxn: Statins + CYP3A4

Which statins ↑ levels of CYP3A4 substrates?

A

Lovastatin
Simvastatin
Atorvastatin

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18
Q

Common Cardiovacular Drug Intxn: Statins + CYP3A4

Which statins are contraindicated w/ strong CYP3A4 inhibitors?

A

Lovastatin
Simvastatin

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19
Q

Brand:Generic

Altoprev

A

lovastatin

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20
Q

Common Cardiovacular Drug Intxn

CYP2C9 inhibitors

A

Azole
Bactrim
Amiodarone
Metronidazole

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21
Q

Common Cardiovacular Drug Intxn

CYP2C9 inducers

A

rifampin
St. John’s wort
Phenobarbital
Phenytoin
Primidone

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22
Q

Common Cardiovacular Drug Intxn

What do CYP2C9 inhibitors cause warfarin to do?

A

↑ warfarin levels → ↑ INR & bleeding

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23
Q

Common Cardiovacular Drug Intxn

What do CYP2C9 inducers cause warfarin to do?

A

↓ warfarin levels → ↓ INR & clotting

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24
Q

Inhibitors ↑ substrate Drugs

Which opiods are metabolizedf by CYP3A4?

A

Fentanyl
Hydrocodone
Oxycodone
Methadone

Do NOT use w/ CYP3A4 inhibitors

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25
Q

Inhibitors ↑ substrate Drugs

What drugs have specific instruction not to take w/ grapefruit?

A

amiodarone
simvastatin
lovastatin
nifedipine
tacrolimus

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26
Q

Inhibitors ↑ substrate Drugs

Valproate + Lamotrigine Intxn

A

Valproate ↓ lamotrigine metabolsim → ↑ risk of skin reactions

Use starter kit w/ lower doses

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27
Q

Inhibitors ↑ substrate Drugs

MAO inhibitors

A

Isocarboxazid
Phenelzine
Tranylcypromine
Rasagiline
Selegiline
Linezolid
Methylene blue

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28
Q

Inhibitors ↑ substrate Drugs

How long is the washout period for MAO inhibitors?

A

2 weeks

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29
Q

Inhibitors ↑ substrate Drugs

Which MAO inhibitor is the exception for the normal washout period?

A

Fluoxetine: 5 weeks

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30
Q

Inhibitors ↑ substrate Drugs

Drugs/Foods that ↑ catecholamines (Epi, NE, DA)

A

bupropion
SNRIs
TCAs
stimulants
levodopa
tyramine (from food)

Can cause hypertensive crisis

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31
Q

Inhibitors ↑ substrate Drugs

Drugs/Foods that ↑ 5-HT

A

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

Opioids & analgesics: fentanyl, methadone, tramadol

Others: buspirone, lithium, dextromethorphan (high doses), St. John’s wort

Can cause serotonin syndrome

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32
Q

Brand:Generic

Remeron

A

mirtazapine

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33
Q

Inhibitors ↑ substrate Drugs

CYP2D6 inhibitors

A

Amiodarone,
fluoxetine,
paroxetine,
fluvoxamine

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34
Q

Inhibitors ↑ substrate Drugs

CYP2D6 substrates

A

codeine
meperidine
tramdol
tamoxifen

Just some examples

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35
Q

Inhibitors ↑ substrate Drugs

Calcineurin inhibitors should be avoided with?

(Tacrolimus, cyclosporine)

Also mTOR kinase inhibitors (Sirolimus, everolimus)

A

CYP3A4 & P-gp inhibitors & inducers

Inhibitors: ↓ drug substrate metabolism
Inducers: ↑ risk of transplant rejection

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36
Q

Inducers ↓ substrate Drugs

Antiepileptic drugs CYP inducers

A

Phenytoin
Phenobarbital
Primidone
Carbamazepine (self inducer)
Oxcarbazepine

Some CYP substrates: Oral contraceptives, other AEDs, carbamazepine

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37
Q

Inducers ↓ substrate Drugs

Inducer that interacts w/ CYP & P-gp substrates

A

Rifampin

38
Q

Inducers ↓ substrate Drugs

CYP2D6 UMs

A

Prodrugs that are CYP2D6 substrates will be more rapidly converted
↑ active drug concentration

Not in inducer

Prodrugs: codeine, tramadol

39
Q

Inducers ↓ substrate Drugs

Do not use codeine or tramadol for?

A

Children < 12 y/o or < 18 y/o following tonsillectomy and/or adenoidectomy (Contraindicated)

OR

Breast-feeding mothers (unless it is known she is not 2D6 UM)

40
Q

Inducers ↓ substrate Drugs

Smoking Interacts with?

A

CYP1A2 substrates:
Some Antipsychotics
Antidepressants
Hypnotics
Anxiolytics
Caffeine
Theophylline
Wafarin (R-isomers)

Smoking is an CYP1A2 inducer

41
Q

Additive Risk:

Drugs that can cause Serotonergic Toxicity

A

Antidepressants
MAO inhibitors
Opioids
Triptans
Natural Products
Others: buspirone, lithium dextromethrophan (high dose)

42
Q

Additive Risk: Serotonergic Toxicity

Antidepressants

A

SSRIs
SNRIs
TCAs
mirtazapine
trazodone

43
Q

Additive Risk: Serotonergic Toxicity

MAO inhibitors

A

Antidepressants: isocarboxazid, phenelzine, tranylcypromine

Selective MAO-B inhibitors: selegiline, rasagiline

Otheres: linezolid, methylene blue

44
Q

Additive Risk: Serotonergic Toxicity

Opioids

A

Fentanyl
Meperidine
Methadone
Tramadol
Tapentadol

45
Q

Additive Risk: Serotonergic Toxicity

Natural products

A

St. John’s wort
L-tryptophan

46
Q

Additive Risk: Serotonergic Toxicity

Symptoms

A

Autonomic dysfxn: diaphoresis, N/V, hyperthermia

Altered mental status: akathisia, anxiety, agitation, delirium

Neuromuscular excitation: hyperreflexia, tremor, rigidity, tonic-clonic seizures

Akathisia: inability to remain still

47
Q

Drugs that ↑ bleeding risk

A

Anticoagulants
Antiplatelets
NSAIDs
SSRIs
SNRIs
Natural products: 5Gs, Vit E, willow bark, fish oils (high doses)

May or May not effect INR

48
Q

Drugs that can cause hyperkalemia

A

Renin-angiotensin-aldosterone system drugs
ACE, ARBs, aliskiren, Entresto, spironolactone, eplerenone (highest risk)

Potassium-sparing diuretis
amiloride, triamterene

Others
Salt substitutes (KCl), calcineurin inhibitors (tacrolimus, cyclosporine), Bactrim, canagliflozin, drospirenone-containing oral contraceptives

49
Q

Drugs that cause QT prolongation

Antiarrhythmics

A

Class Ia, Ic, III

50
Q

Drugs that cause QT prolongation

Anti-infectives

A

Antimalarials (hydroxychloroquine)
Azole antifungals (except isavuconazonium)
Lefamulin
Macrolides
Quinolones

51
Q

Drugs that cause QT prolongation

Antidepressants

A

SSRIs (highest w/ citalopram, escitalopram)
TCAs
mirtazapine
trazodone
venlafaxine

52
Q

Drugs that cause QT prolongation

Antipsychotics

A

1st gen: haloperidol, thioridazine
2nd gen: highest risk w/ ziprasidone

53
Q

Drugs that cause QT prolongation

Antiemetics

A

5-HT3 receptor antagonists (ondansetron)
droperidol
metoclopramide
promethazine

54
Q

Drugs that cause QT prolongation

Oncology Meds

A

Androgen deprivation therapy (leuprolide)
Tyrosine kinase inhibitors (nilotinib)
oxaliplatin

55
Q

Drugs that cause QT prolongation

Others

A

cilostzol
denpezil
fingolimod
hydroxyzine
loperamide
ranolazine
solifenacin
methadone
tacrolimus

56
Q

QT prolongation

Citalopram dose

A

40 mg QD
20 mg QD for > 60 y/o

57
Q

QT prolongation

Escitalopram dose

A

20 mg QD
10 mg QD for > 60 y/o

58
Q

QT prolongation

DOC to treat arrhythmia in pts w/ HF?

A

amiodarone

59
Q

QT prolongation

Which SSRI is the safest in pts w/ CVD?

A

sertraline

60
Q

QT prolongation

What antiemetic should not be use for inpatient N/V?

A

droperidol

61
Q

CNS Depression

What drugs are highest risk for fatality when used in combo?

A

Opiods + benzodiazepines

Or othe CNS depressants including alcohol

62
Q

CNS Depression

Effects

A

somnolence
dizziness
confusion/cognitive impairment
altered consciousness/deliriums
gaint instability/imbalance/risk of falls/accidents

63
Q

What drugs can cause ototoxicity?

Hearing loss, tinnitus, vertigo

A

Aminoglycosides: gentamicin, tobramycin, amikacin

Cisplatin

Loop diuretics: furosemide, bumetanide, ethacrynic acid

Salicylates: aspirin, salsalte, magnesium salicylate

Vancomycin

64
Q

What drugs can cause nephrotoxicity?

↑ SCr/BUN

A

Anti-infectives: aminoglycosides, amphotericin B, polymyxins

cisplatin

Calcineurin inhibitors: cyclosporine, tacrolimus

Loop diuretics: furosemide, torsemide, bumetanide, ethacrynic acid

NSAIDs

Radiographic-contrast dye

65
Q

What drug w/ cisplatin to protect kidneys?

A

amifostine (Ethyol)

66
Q

Anticholinergic Toxicity

Antidepressants/antipsychotics

A

paroxetine
TCAs
1st-gen antipsychotics

67
Q

Anticholinergic Toxicity

Sedating antihistamines

A

diphenhydramine
bromphenbiramine
chlorpheniramine
doxylamine
hydroxyzine
cyproheptadine
meclizine

68
Q

Anticholinergic Toxicity

Centrally-acting anticholinergics

A

benztropine
trihexyphenidyl

69
Q

Anticholinergic Toxicity

Muscle Relaxants

A

baclofen
carisoprodol
cyclobenzaprine

70
Q

Anticholinergic Toxicity

Antimuscarinics

For urinary incontinence

A

oxybutynin
darifenacin
tolterodine

71
Q

Anticholinergic Toxicity

Others

A

atropine
belladonna
dicyclomine

72
Q

Who are at the highest risk of anticholinergic toxicity?

A

Elderly

73
Q

Side effects of PDE-5 inhibitors & CYP3A4 inhibitors

A

HA
dizziness
flushing
↑ risk of falls/injury

74
Q

When starting a PDE-5 inhibitors when a patient is already on a CYP3A4 inhibitor?

A

1/2 the starting dose of the PDE-5 inhibitor

Same for PDE-5 inhibitors w/ alpha-1 blockers

75
Q

PDE-5 inhibitors, _ , & _ causes vasodilation leading to hypotension/orthostasis

A

nitrates & alpha-1 blockers

76
Q

PDE-5 inhibitors are CI w/?

A

Nitrates

Causes severe hypotension

77
Q

CYP3A4 substrates

A

Analgsics: fentanyl, hydrocodone, methadone, oxycodone
Anticoagulants: apixaban, rivaroxaban, R-warfarin
Cardiovascular drugs: amiodarone, amlodipine, diltiazem, verapamil
Immunosupressants: cyclosporine, tacrolimus, sirolimus
Statins: atorvastatin, lovastatin, simvastatin
HIV drugs: NNRTIs
PDE-5 inhibitors: avanafil, sildanfil, tadlafil, vardenafil
Others: ethinyl estradiol

78
Q

CYP1A2 substrates

A

theophylline
R-warfarin

79
Q

CYP1A2 Inducers

A

Carbamazepine
Phenobarbital
Phenytoin
Rifampin
Smoking
St. John’s wort

Also CYP2C9 inducers

80
Q

CYP1A2 Inhibitors

A

Ciprofloxacin
Fluvoxamine

81
Q

CYP2C9 substrate

A

S-warfarin

82
Q

CYP2C9 inhibitors

A

amiodarone
fluconazole
metronidazole
Bactrim

83
Q

CYP2C19 substrate

A

clopidogrel

84
Q

CYP2C19 inhibitors

A

esomeprazole

omeprazole

85
Q

CYP2D6 substrates

A

Analgesics: codeine, meperidine, tramadol
Antipsychotics/Antidepressants
Others: tamoxifen

86
Q

CYP2D6 inhibitors

A

amiodarone
duloxetine
fluoxetine
paroxetine

87
Q

Brand:Generic

Restoril

A

temazepam

88
Q

Brand:Generic

Aggrenox

A

Acetylsalicylic acid + Dipyridamole

Blood thinner

89
Q

Brand:Generic

Lotensin

A

Benazepril

90
Q

Brand:Generic

Lotrel

A

Amlodipine / Benazepril

91
Q

Brand:Generic

Yasmin

A

Drospirenone / Ethinyl estradiol

Other Brands: Loryna, Vestura, Yasmin, Gianvi, YAZ, Nikki, Zarah, Syeda, and Ocella