NAPLEX - DRUG INTERACTIONS

benzodiazepines, opioids

________s and ________s can have an additive effect that can lead to fatal CNS depression. Therefore, there is a BBW warning for all drugs in these classes when used in combination

chelation

When a drug binds to polyvalent cations

fluoroquinolones, tetracyclines, levothyroxine, bisphosphonates (obvi PO bisphosphonates)

Give 4 drugs/drug classes that should be separated from polyvalent cations

sodium bicarbonate

In the event of salicylate overdose, IV ____ ____ can help increase salicylate clearance

probenacid

_____ blocks the renal clearance of penicillin and can help achieve higher concentrations in the CNS

phase 1

CYP450 enzymes participate in (phase 1/phase2?) metabolism

liver

Where are cyp enzymes produced?

CYP3A4

Which CYP enzyme?

metabolizes 34% of all CYP substrates, one of the most common mediators of DDIs

lisdexamfetamine (cannot be crushed/snorted because it must be hepatically activated)

_______ is a prodrug used for ADHD that is abuse-deterrent as a result of its status as a prodrug

CYP2D66 ultra-rapid metabolizer

What pharmacogenomic status can cause toxicity with codeine (too high levels of active drug)?

CYP2D6 poor metabolizer

What pharmacogenomic status can cause lack of efficacy with codeine (too low levels of active drug)?

CYP2C19 inhibitors

Clopidogrel should not be co-administered with what class of medications in order to prevent treatment failure (regarding PK interactions/CYP stuff)?

CYP2C19 inducers

Clopidogrel should not be co-administered with what class of medications in order to mitigate risk of bleeding/supratherapeutic levels (regarding PK interactions/CYP stuff)?

B

A CYP2C19 poor metabolizer would be most likely to experience which of the following?

(a) High clopidogrel levels, leading to bleeding

(b) Low active metabolite of clopidogrel levels, leading to treatment failure

A

A CYP2C19 ultra-rapid metabolizer would be most likely to experience which of the following?

(a) High active metabolite of clopidogrel levels, leading to bleeding

(b) Low clopidogrel levels, leading to treatment failure

B

A CYP2D6 poor metabolizer would be most likely to experience which of the following?(codeine)

(a) High active drug levels, leading to respiratory depression

(b) Low active drug levels, leading to poor pain control

A

(Codeine)A CYP2D6 ultra-rapid metabolizer would be most likely to experience which of the following?

(a) High active drug levels, leading to respiratory depression

(b) Low active drug levels, leading to poor pain control

Valganciclovir

Give the prodrug of the following drug:

ganciclovir

Valacyclovir

Give the prodrug of the following drug:

acyclovir

primidone

Give the prodrug of the following drug:

phenobarbital

prednisone

Give the prodrug of the following drug:

prednisolone

lisdexamfetamine

Give the prodrug of the following drug:

dextroamphetamine

levodopa

Give the prodrug of the following drug:

dopamine

isavuconium sulfate

Give the prodrug of the following drug:

isavuconazole

fosphenytoin

Give the prodrug of the following drug:

phenytoin

Famciclovir

Give the prodrug of the following drug:

penciclovir

cortisone

Give the prodrug of the following drug:

cortisol

colistimethate

Give the prodrug of the following drug:

colistin

codeine

Give the prodrug of the following drug:

morphine

capecitabine

Give the prodrug of the following drug:

5-fluorouracil

UGT (ex UGT1A1 and bictegravir), NAT

Give the main 2 enzyme classes that have PK ramifications that are involved in phase 2 metabolism

clopidogrel, tramadol

Give two drugs that are prodrugs and have no activity on their own listed in the book (sorry, I know this question sucks)

inhibitors

grapefruit, protease inhibitors, azoles, cyclosporin, cobicistat, macrolides, amiodarone, non-DHP CCBs

G PACMAN is a helpful acronym for CYP _____s.

Expand the acronym

G PACMAN

The acronym from the book for CYP inhibitors

PS PORCS

The acronym from the book for CYP inducers

inducers

phenytoin, smoking, phenobarbital, oxcarbazepine, rifampin, carbamazepine, St. John's wort

PS PORCS is a helpful acronym for CYP _____s.

Expand the acronym

TRUE

TRUE or FALSE: DDIs that involve inhibitors exhibit their effects more quickly than inducers

digoxin, warfarin

Common CV Drug Interactions

Amiodarone

Give 2 CV-related drugs to watch

CYP2C9

The main metabolizing enzyme of warfarin

loop diuretics, amiodarone

Common CV Drug Interactions

Digoxin

Give 2 CV-related drugs to watch

CYP2C9

decrease

The enzyme/pump that is the cause of the DDI between warfarin and amiodarone. Adding amiodarone to warfarin will likely lead to a necessary dose (increase/decrease) in warfarin

PGP

decrease

The enzyme/pump that is the cause of the DDI between digoxin and amiodarone. Adding amiodarone to digoxin will likely lead to a necessary dose (increase/decrease) in digoxin

30-50%

If a patient is on warfarin and needs to add amiodarone, a dose decrease of ___-___% of warfarin will likely be needed

5 mg (or less)

If a patient is on amiodarone and needs to add warfarin, what is the max starting dose of warfarin?

50%

If a patient is on amiodarone and needs to add digoxin, a dose decrease of ____% of digoxin will likely be needed

0.125-0.25 mg daily

If a patient is on digoxin and needs to add amiodarone, what is the starting dosing range of digoxin?

nausea, vomiting, vision changes

Give 3 signs/sx of digoxin toxicity

digoxin

Loop diuretics should be used in caution with the antiarrhythmic _______, because electrolyte abnormalities (low K/mg, high Ca) can lead to higher risk of toxicity with this drug

beta blockers, non-DHP calcium channel blockers, amiodarone, clonidine, digoxin (also precedex)

Drugs that decrease heart rate:

Give 5 drugs/drug classes that, when used in combination, can cause bradycardia

lovastatin, simvastatin, atorvastatin (atorva lease of these 3; sim + lova are contraindicated with strong CYP3A4 inhibitors)

The three primary statins that are CYP3A4 substrates

lovastatin, simvastatin

The two statins that are contraindicated with strong cyp3a4 inhibitors

carbamazepine, rifampin, oxcarbazepine, phenytoin, phenobarbital, St. John's wort, smoking (acronym CROPPSS)

Give the 7 main CYP inducers

oxcarbazepine

CYP3A4

There are 7 main cyp inducers: carbamazepine, rifampin, oxcarbazepine, phenytoin, phenobarbital, St. John's wort, smoking (acronym CROPPSS). All of them induce CYP3A4, CYP1A2, and CYP2C9 except _____. This drug only inhibits _____

methadone, oxycodone, fentanyl, hydrocodone

Give the 4 analgesics that are CYP3A4 substrates

apixaban, rivaroxaban (technically R-warfarin too)

Give the 2 anticoagulants that are CYP3A4 substrates

amiodarone, amlodipine, diltiazem, verapamil

Give the 4 CV drugs that are CYP3A4 substrates

cyclosporine, tacrolius, sirolimus

Give the 3 immunosuppressants that are CYP3A4 substrates

avanafil, sildenafil, tadalafil, vardenafil

Give the 4 PDE-5 inhibitors that are CYP3A4 substrates

ethinyl estradiol

What common contraceptive component is a CYP3A4 substrate?

clarithromycin, erythromycin, azole antifungals, amiodarone, diltiazem, verapamil, cobicistat, ritonavir (and other protease inhibitors), cyclosporine, grapefruit (CADAVER CCG if that's helpful lol)

Give 10 CYP3A4 inhibitors (sorry)

esomeprazole, omeprazole

Give 2 CYP2C19 inhibitors

amiodarone, duloxetine, fluoxetine, paroxetine

Give 4 CYP2D6 inhibitors

codeine, meperidine, tramadol, tamoxifen

Give 4 CYP2D6 substrates

Amiodarone, fluconazole, metronidazole, bactrim (TMP/SMX)

Give 4 CYP2C9 inhibitors

fluvoxamine, ciprofloxacin

Give 2 CYP1A2 inhibitors

amiodarone, simvastatin, lovastatin, nifedipine, tacrolimus (SLANT)

Give 5 drugs that have specific instructions not to take with grapefruit (ones from the book)

valproate

_____ is an inhibitor of lamotrigine metabolism, potentially causing SJS/TEN

monoamine oxidase inhibitors (MAOis; idk why the naplex book is kinda obsessed with these)

Give the drug class of the following agents:

Isocarboxazid, phenelzine, tranylcypromine, rasagiline, selegiline

epinephrine, norepinephrine, serotonin, dopamine

MAOis should not be taken with drugs that increase the concentration of what four substances?

tyramine

_____-rich foods, including aged cheese, air-dried meats, and sauerkraut, can cause a hypertensive crisis in combination with MAOis

inducers

AEDs tend to have a lot drug-drug interactions because they are commonly CYP (inducers/inhibitors).

neuromuscular excitation, autonomic dysfunction, altered mental status

Give the 3 classes of symptoms/signs of serotonin syndrome

ok

Just FYI

Serotonin Syndrome =

neuromuscular excitation -> rigidity, hyperreflexia, tremor, tonic-clonic seizures

autonomic dysfunction -> diaphoresis, nausea, vomiting, hyperthermia

altered mental status - agitation, anxiety, akathisia, delirium (say ok)

garlic, ginger, ginkgo, ginseng, glucosamine

Give the "5 G's", or the 5 natural products that can increase bleeding risk

linezolid, methylene blue, antidepressants, MAOis, opioids, triptans, natural products (St. John's wort, L-tryptophan; also buspirone, lithium, dextromethorphan, vitamin E, willow bark, fish oils)

Give 7 drugs/drug classes that, when used in combination, can increase risk for serotonin syndrome

ace/arbs, ARAs, potassium-sparing diuretics, bactrim, calcineurin inhibitors (also KCl salt substitutes, canagliflozin, drospirenone)

Give 5 drug classes that can cause hyperkalemia, especially in combination

antiarrhythmics, azole antifungals, macrolides, fluoroquinolones, antidepressants, antipsychotics, antiemetics (also donepezil, methadone, fingolimoid)

Give 7 drug classes that can cause QTc prolongation

Torsades de pointes

The main concern with QT prolongation is that it can lead to what potentially fatal arrhythmia?

40 mg 20 mg

20 mg 10 mg

sertraline

droperidol

QT prolongation:

1. Do not exceed citalopram doses of ______ (or ____ in the elderly)

2. Do not exceed escitalopram doses of ______ (or ____ in the elderly)

3. ____ is the safest SSRI in CVD

4. Do not use _____ for inpatient N&V

benzodiazepines, opioids

The drug combination that has the highest risk of CNS depression

alcohol

Recreational use of _____ is not recommended in combination with BZDs/opioids

TRUE

TRUE or FALSE: ER opioid products are high risk with alcohol and can tend to behave more like short-acting formulations when combined with alcohol

ok

CNS depressant effects: somnolence, dizziness, confusions, cognitive impairment, altered consciousness, risk of falls (say ok)

aminoglycosides, vancomycin, cisplatin, loop diuretics, salicylates

Give 5 drug classes that can cause ototoxicity

hearing loss, vertigo, tinnitus

Give 3 signs/symptoms of drug-induced ototoxicity

anti-infectives (aminoGs, vanc, amphoB, polymix), cisplatin, calcineurin inhibitors, loop diuretics, NSAIDs, contrast

Give 5 drug classes that can cause nephrotoxicity

amifostine (ethyol)

_____ can be used to mitigate the nephrotoxicity risk of cisplatin

antidepressants, antipsychotics, antihistamines (sedating, first-gen), anticholinergics (benztropine, trihexyphenidyl), muscle relaxants, antimuscarinics (oxybutynin, tolterodine)

Give 6 drug classes that have anticholinergic properties.

elderly

Anticholinergic drugs should be avoided in what population?

PDE-5 inhibitors, nitrates, alpha-1 antagonists

Give 3 drug classes that can cause orthostatic hypotension, especially in combination

nitrates

PDE-5 inhibitors are contraindicated in combination with what drug class?

starter kits (3 kits that I could find- NOT on other anticonvulsants, on valproate, on an anticonvulsant that isn't valproate)

An important thing to know about lamotrigine is that there are different ____ _____s for patients on other anticonvulsants.

apixaban, rivaroxaban, digoxin, diltiazem, verapamil, cyclosporine, tacrolimus, colchicine

Give 8 PGP substrates

SSRIs, SNRIs

In addition to common offenders (warf, DOACs, ASA, NSAIDs), what 2 common drug classes can increase bleeding risk?

theophylline (R-warfarin too)

Give the main CYP1A2 substrates to know

pravastatin

The statin with the least risk of a DDI