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NAPLEX 2023 > Chapter 3: Learning Drug Interactions > Flashcards

Chapter 3: Learning Drug Interactions Flashcards

1
Q

What is pharmacodynamics

A

The effect or change that a drug has on some type of organism, such as a human body

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2
Q

What is a pharmacodynamic drug interaction

A

When 2 or more drugs are given together and their end effects impact each other

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3
Q

Concomitant use of which 2 drug classes has a BBW that they may result in profound sedation, respiratory depression, coma and death

A

BZDs and opioids

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4
Q

____ is present when the effect from 2 drugs taken in combination is greater than the effect from simply adding the 2 individual effects together

A

Synergism

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5
Q

What is pharmacokinetics?

A

The effect the body has on the drug

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6
Q

What does ADME stand for

A

Absorption
Distribution
Metabolism
Excretion

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7
Q

What is chelation

A

when a drug binds to polyvalent cations (e.g., Mg, Ca, Fe) in another compound (e.g., antacids or iron supplements). The chelated complex cannot dissolve in the gut fluid and will pass out in the stool

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8
Q

Drugs with polyvalent cations or other binding properties should be separated from:

A

quinolones, tetracyclines, levothyroxine, and oral bisphosphonates

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9
Q

The majority of PK drug interactions occur during ____ in the _____

A

metabolism in the liver

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10
Q

____ is the primary route of drug excretion

A

Renal excretion

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11
Q

CYP450 enzymes are primarily expressed in the ____

A

liver

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12
Q

Which CYP enzyme metabolizes ~34% of all CYP-metabolized drugs

A

3A4

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13
Q

Prodrugs are taken by the patient in the ____ form and are converted by CYP450 enzymes into the ____ form

A

inactive
active

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14
Q

Codeine and tramadol should not be used in ultra-rapid metabolizers of ___

Why?

A

2D6

These prodrugs will be converted more rapidly to active drug, and with increased active drug concentration, this can cause toxicity/risk of possible fatality

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15
Q

Do not use clopidogrel with ____ inhibitors, including ___ and ____

A

2C19 inhibitors, including omeprazole and esomeprazole

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16
Q

With a prodrug, the active drug concentration decreases with a(n) _____

A

inhibitor (opposite effect since there are less functional enzymes to convert the prodrug to the active form)

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17
Q

What are the major CYP inhibitors

A

Remember G <3 PACMAN

  • Grapefruit
  • <3
  • Protease inhibitors (PI), especially ritonavir
  • Azole antifungals (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, and isavuconazole)
  • Cyclosporine, cimetidine, cobicistat
  • Macrolides (clarithromycin and erythromycin, but not azithromycin)
  • Amiodarone (and dronedarone)
  • Non-DHP CCBs (diltiazem and verapamil)
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18
Q

What are the major CYP inducers

A

Remember PS PORCS

  • Phenytoin
  • Smoking
  • Phenobarbital
  • Oxcarbazepine (and eslicarbazepine)
  • Rifampin (and rifabutin, rifapentine)
  • Carbamazepine (also an auto-inducer)
  • St. John’s Wort
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19
Q

T/F: enzyme inhibition is fast & effects are seen within a few days and will end quickly when the inhibitor is d/c

A

True

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20
Q

When the inducer is stopped, it could take ____ for the induction effects to disappear completely

A

2-4 weeks

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21
Q

P-gp pumps in the cell membranes of the GI tract transport drugs and their metabolites out of the body by pumping them into the ___, where they can be excreted in the ____

A

gut
stool

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22
Q

When a drug inhibits Pgp, a drug that is a P-gp substrate will have (increased/decreased) absorption and the substrate drug level will (increase/decrease)

A

increased

increase

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23
Q

Common Pgp substrates per class:

  • anticoagulants
  • CV drugs
  • immunosuppressants
  • HCV drugs
  • Others
A
  • anticoagulants: apixaban, rivaroxaban
  • CV drugs: digoxin, diltizaem, verapamil
  • immunosuppressants: cyclosporine, tacrolimus
  • HCV drugs: ombitasvir, paritaprevir, dasabuvir
  • Others: colchicine
24
Q

The recycling of an already-metabolized drug is called ______, which (increases/decreases) the duration of action of many drugs

A

enterohepatic recycling

increases

25
Q

Amiodarone (inhibits/induces) multiple enzymes, including ____, which metabolizes the major warfarin isomer.

What action should be taken by the pharmacist?

A

Inhibits
CYP2C9

If using amiodarone first and adding warfarin: start warfarin at a lower dose of = 5 mg

If using warfarin first and adding amiodarone: decrease warfarin dose 30-50%, depending on the INR

26
Q

Amiodarone inhibits P-gp and digoxin is a P-gp substrate. They also both increase the risk of ____.

What action should be taken by the pharmacist if using digoxin first and adding amiodarone?

A

Bradycardia; monitor for other drugs that decrease HR like BB, clonidine, diltiazem and verapamil

If using digoxin first and adding amiodarone, decrease the oral digoxin dose 50%

27
Q

What is the interaction between digoxin and loop diuretics

A

Loops decrease K, Mg, Ca and Na. Digoxin toxicity risk is increased with decreased K and Mg levels and increased Ca levels

28
Q

What action should be taken by the pharmacist when a patient is taking a statin and strong CYP3A4 inhibitor

A

Simvastatin and lovastatin are CI. Recommend a statin not metabolized by CYP450 enzymes (pitavastatin, pravastatin, rosuvastatin)

29
Q

CYP2C9 inhibitors (increase/decrease) levels of warfarin, which (increase/decrease) INR and bleeding risk

A

increase levels of warfarin
increase INR

30
Q

CYP2C9 inducers (increase/decrease) levels of warfarin, which (increase/decrease) INR and bleeding risk

A

Decrease levels of warfarin

decrease INR

31
Q

Which drugs specifically include instructions not to take with grapefruit juice

A

Amiodarone, simvastatin, lovastatin, nifedipine, tacrolimus

32
Q

What is the interaction between lamotrigine and valproate

A

Valproate decreases lamotrigine metabolism. Increased lamotrigine levels increase risk of serious skin reactions

33
Q

What is the interaction between MAOi and drugs that increase Epi, NE, and DA and 5-HT

What action should be taken by the pharmacist

A

Blocking MAO with an MAOi will increase Epi, NE, DA and 5HT. High Epi, NE, and DA can cause hypertensive crisis. High 5HT can cause serotonin syndrome.

Use a 2-week washout period between serotonergic drugs and another antidepressant; if changing fluoxetine to an MAOi, wait 5 weeks

34
Q

What is the interaction between MAOi and tyramine-rich foods/drinks

A

MAO metabolizes tyramine; if blocked, tyramine causes increased NE, with risk of hypertensive crisis

35
Q

Which drugs are 2D6 inhibitors

A

Amiodarone, fluoxetine, paroxetine, fluvoxamine

36
Q

Do not use an opioid prodrug that is metabolized by 2D6 (codeine, tramadol) in which patient population

A

Breast-feeding mother

37
Q

What would happen to someone who is a smoker who takes antipsychotics, antidepressants, hypnotics, anxiolytics, caffeine, theophylline, or warfarin and quits?

What about current smokers?

A

Smokers who quit - when the inducer (cigarettes) is stopped, drug concentrations increase and can cause toxicity

Current smokers - the substrate drugs will have decreased levels

38
Q

Which drugs, when used together, can cause serotonergic toxicity

A 
Antidepressants
MAOi
Busprione
Dextromethorphan
Dihydroergotamine
Lithium
Lorcaserin
Opioids
Metoclopramide
Triptans
Natural products (St. John's Wort, I-tryptophan)
Tegaserod
39
Q

Which drugs, when used together, can increase bleeding risk

A 
Anticoagulants
Antiplatelets
NSAIDs
SSRIs/SNRIs
Natural products (5Gs: garlic, ginger, ginkgo biloba, ginseng, glucosamine, plus vitamin E, willow bark, and fish oils)
40
Q

Which drugs, when used together, can cause hyperkalemia risk

A 
Spironolactone, eplerenone - highest risk
RAAS drugs (ACEi, ARBs, aliskiren, sacubitril/valsartan)
Amiloride, triamterene, KCl, tacolimus, cyclosporine, canagliflozin, SMX/TMP, and drosperinone-containing OCs
41
Q

Citalopram and escitalopram are two SSRIs that can increase QT prolongation. What doses of the two should you not exceed in elderly patients > 60 years and in patients < 60?

A

Citalopram 40 mg/day
Citalopram 20 mg/day in patients > 60 years

Escitalopram 20 mg/day
Escitalopram 10 mg/day in patients > 60 years

42
Q

Which combination of drugs has the highest risk of fatality when used in combination

A

Opioids + BZDs or other CNS depressants

43
Q

Which drugs can cause ototoxicity?

A

Aminoglycosides, cisplatin, loop diuretics (especially rapid IV administration), salicylates, vancomycin

44
Q

Which drugs can cause nephrotoxicity?

A 
Aminoglycosides, amphotericin B, polymyxins, vancomycin
Cisplatin
CNIs: cyclosporine, tacrolimus
Loop diuretics (especially IV)
NSAIDs
Radiographic-contrast dye
45
Q

Which drugs can cause anticholinergic toxicity?

A

Paroxetine, TCAs, FGAs
Sedating antihistamines: diphenhydramine, brompheniramine, chlorpheniramine, doxylamine, hydroxyzine, cyproheptadine
Atropine, belladonna, dicyclomine, meclizine
Benztropine, trihexyphenidyl
Muscle relaxants, including baclofen, carisoprodol, cyclobenzaprine
Overactive bladder antimuscarinics, such as oxybutynin, darifenacin, tolterodine

46
Q

CYP3A4 substrates

A

Analgesics: fentanyl, hydrocodone, methadone, oxycodone
Anticoagulants: apixaban, rivaroxaban, R-warfarin
CV drugs: amlodipine
Immunosuppressants: cyclosporine, tacrolimus, sirolimus
Statins: atorvastatin, lovastatin, simvastatin
PDE5i: avanafil, sildenafil, tadalafil, vardenafil
Others: ethinyl estradiol

47
Q

CYP3A4 inducers

A

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

48
Q

CYP3A4 inhibitors

A

Anti-infectives: clarithromycin, erythromycin, azole antifungals
CV drugs: amiodarone, diltiazem, verapamil
Key HIV drugs: cobicistat, ritonavir and other protease inhibitors
Others: cyclosporine, grapefruit juice

49
Q

1A2 substrates

A

R-warfarin

50
Q

1A2 inducers

A

Carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort

51
Q

1A2 inhibitors

A

Cipro, fluvoxamine

52
Q

2C9 substrates

A

S-warfarin

53
Q

2C9 inducers

A

Carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort

54
Q

2C9 inhibitors

A

Amiodarone, fluconazole, metronidazole, SMX/TMP

55
Q

2C19 substrate

A

Clopidogrel

56
Q

2C19 inhibitors

A

Esomeprazole, omeprazole

57
Q

2D6 substrates

A

Codeine, meperidine, tramadol, tamoxifen

NAPLEX 2023 (88 decks)

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