Lecture 6: Drug Interactions Flashcards

1
Q

What are the common risk factors associated with drug interactions?

A

Polypharmacy
Multiple prescribers
Multiple pharmacies
Genetic makeup
Special populations
Drug makeup

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2
Q

What is the definition of a drug interaction?

A

Modification of the effect of one drug by the prior concomitant administration of another drug.

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3
Q

What are the drug - dietary supplement interactions?

A

Rx, OTC, illicit substances
St. John’s Wort
Cocaine & antiHTNs

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4
Q

What are the drug - food or drink interactions?

A

Doxycycline & milk
Metronidazole and alcohol

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5
Q

What are the drug - disease interactions?

A

Beta blockers & asthma
NSAIDs & heart failure

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6
Q

What are the categories of Drug Interaction Severity?

A

Category A: Unknown, no known interaction
Category B: Minor, No action needed. Minimal effect.
Category C: Moderate, monitor, may require adjustments.
Category D: Major, consider alternative, may be life-threatening.
Category X: Contraindicated, avoid combination, no concurrent use allowed.

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7
Q

What are the pharmacodynamic drug interactions?

A

Additive effects on same receptor or additive effects on different receptors.
Synergistic effects (aminoglycosides + penicillin)
Antagonist blocking agonist effects (Naloxone for opioids)

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8
Q

What are some of the additive interactions pharmacodynamically?

A

Increased bleeding risk

Anticholinergic toxicity

Nephrotoxicity

QT Prolongation

Serotonergic Agents

Hyperkalemia (increased potassium)

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9
Q

What drugs can cause increased bleed risk additively?

A

Anticoagulants like warfarin and DOACs (direct oral anticoagulants like rivaroxaban or apixaban or dabigatran)
Antiplatelets like clopidogrel/ticagrelor/prasugrel/aspirin
NSAIDs, SSRIs (Prozac, Lexapro, Zoloft), and SNRIs (Duloxetine, Venlafaxine)
Natural Products AKA the 5 Gs: garlic, gingko, ginger, ginseng, glucosamine.

Note:
Rivaroxaban = Xarelto
Apixaban = Eliquis
Dabigatran = Pradaxa
Clopidogrel = Plavix
Ticagrelor = Brilinta
Prasugrel = Effient
Duloxetine = Cymbalta
Venlafaxine = Effexor

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10
Q

What drugs can cause anticholinergic toxicity additively?

A

Antihistamines (diphenhydramine)
SSRIs (Prozac, lexapro, zoloft), antipsychotics (risperidone, olanzapine, aripiprazole), TCAs (amitriptyline)
Muscle relaxants (baclofen)
Overactive bladder antimuscarinics (Oxybutynin)

Note: Relax allergies, mood, muscles, bladder
Diphenhydramine = Benadryl
Prozac = Fluoxetine
Lexapro = Escitalopram
Zoloft = Sertraline
Risperidone = Risperdal
Olanzapine = Zyprexa
Aripiprazole = Abilify
Amitriptyline = Elavil

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11
Q

What drugs can cause nephrotoxicity additively?

A

Aminoglycosides, vancomyin, amphotericin B
NSAIDs
IV Loop diuretics (furosemide, bumetanide, torsemide)
Chemotherapy (cisplatin, methotrexate), cyclosporine, tacrolimus

Note:
All of these drugs require renal clearance or act on the kidney.
Furosemide = Lasix.
Bumetanide = Bumex
Torsemide = Demadex

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12
Q

What drugs can cause QT prolongation additively?

A

Antiarrhythmics - amiodarone, sotalol, dofetilide, ibutilide, procainamide, dronedarone

Antimicrobials - azoles, fluoroquinolones, macrolides

Antipsychotics - haloperidol, quetiapine, ziprasidone

Antidepressants - SSRIs, SNRIs, TCAs

Methadone, sumatriptan, ondansetron

Note:
Haloperidol = Haldol
Quetiapine = Seroquel
SSRI = selective serotonin reuptake inhibitor
SNRI = serotonin norepinephrine reuptake inhibitor
TCA = tricyclic antidepressant
Ondansetron = Zofran

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13
Q

What drugs can boost serotonin additively?

A

All mood-altering meds, such as SSRIs, SNRIs, mirtazapine, trazadone, buspirone, TCAs, MAOis, lithium

Linezolid

Tramadol, methadone, meperidine

Dextromethorphan (cough medication)

Antiemetics (ondansetron)

Triptans (sumatriptan)

Note:
SSRI = selective serotonin reuptake inhibitor
SNRI = serotonin norepinephrine reuptake inhibitor
Mirtazapine = Remeron
TCA = tricyclic antidepressant (think amitriptyline)
MAOi = Monoamine oxidase inhibitor
Meperidine = Demerol (narcotic opioid)
Ondansetron = Zofran

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14
Q

What drugs can cause hyperkalemia additively?

A

ACE inhibitors, ARBs, Sacubitril/Valsartan

K-sparing diuretics

Aldosterone antagonists

Sulfamethoxazole/trimethoprim

Tacrolimus/cyclosporine

Note:
ARB = angiotensin receptor blocker
Sacubitril/valsartan = Entresto (heart failure med)

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15
Q

What are the four ways to affect absorption via drug interactions?

A

Chelation/complex formation
Change in pH
Increased motility time
p-gp efflux pumps

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16
Q

What are the two ways to affect distribution via drug interactions?

A

Binding to alpha-1 acid glycoproteins
Binding to albumin

17
Q

What are the two ways to affect elimination via drug interactions?

A

Competition for transport
Change in urinary pH

18
Q

What are the CYP Inducers?

A

SCRAP GPS’S

Sulfonylureas (T2DM drugs)
Carbamazepine (antiseizure)
Rifampin/rifabutin (Abx for TB)
Alcohol use (chronic)
Phenobarbital (antiseizure)
Griseofulvin (antifungal)
Phenytoin (antiseizure)
Smoking
St. John’s Wort

19
Q

What are the CYP inhibitors?

A

PACMAN’S GM

Protease inhibitors (Anti HIV)
Amiodarone (antiarrhythmic)
Cyclosporine (immunosuppressant), chlorophenol (pesticide), cimetidine (GERD)
Macrolides (except azithromycin, Abx)
Azoles (antifungals)
Non-DHP CCBs (antiarrhythmics)
Sodium Valproate (antiseizure)
Grapefruit Juice
Metronidazole (Abx)

20
Q

What drugs are 3A4 substrates?

A

Analgesics, anticoagulants (ACs), Antiplatelets, Antidiabetics, CV drugs, Immunosuppressants, Statins, HIV drugs, PDE-5 Inhibitors, Others

21
Q

What drugs are 2D6 substrates?

A

Analgesics, Antidepressants/antipsychotics, and others

22
Q

How much of the top 200 drugs are NOT metabolized by CYP enzymes?

A

33%, mostly via phase II metabolism.

Note:
Non-CYP metabolism usually has less drug interactions.
Most common are via UDP, NAT, and MAO.

23
Q

What toxicity can occur via Non-CYP enzyme metabolism?

A

Isoniazid toxicity

24
Q

What are some p-gp substrates?

A

Anticoagulants (apixaban, rivaroxaban, and dabigatran)
Antineoplastics (Docetaxel, vincristine)
Immunosuppressants (cyclosporine, tacrolimus)
Macrolides (clarithromycin)
HIV drugs (dolutegravir)
Digoxin

25
Q

What are some p-gp Inhibitors?

A

Antibiotics (clarithromycin, itraconazole, posaconazole)
HIV drugs (cobicistat, ritonavir)
Cardio drugs (verapamil, amiodarone, dronedarone, diltiazem)
Cyclosporine
Ticagrelor (Brilinta)

ABCCH

26
Q

Why do we use prodrugs?

A

We can use the CYP enzyme to convert it to the active metabolite, saving us money.
Reduces drug abuse, increases bioavailability
Risk lack of activity or potential toxicity

27
Q

What are the common prodrugs?

A

Codeine => morphine
Clopidogrel => active form
Lisdexamphetamine=> dexamphetamine
Fosphenytoin => phenytoin
Enalapril => enalaprilat
Valacyclovir => acyclovir
Cortisone => cortisol
Prednisone => Prednisolone
Primidone => Phenobarbital
Tramadol => active
Levodopa => dopamine
Diazepam = Oxazepam

28
Q

What are the common narrow therapeutic index drugs?

A

Aminoglycosides (G- ABx)
Vancomycin (ABx)
Digoxin (antiarrhythmic)
Warfarin (AC)
Tacrolimus (immunosuppressant)
Mycophenolate (immunosuppressant)
Cyclosporine (immunosuppressant)
Phenytoin (antiseizure)
Valproic acid/Sodium valproate (antiseizure)
Carbamazepine (antiseizure)
Theophylline (Bronchodilator)
Lithium (antimania)
Levothyroxine (HYPOthyrodism)

29
Q

What are the four ways we can affect warfarin via drug interactions?

A

Increased bleed risk via other ACs, NSAIDs, or SSRIs
Metabolism Interference via ABCDEF/Rifampin
Reduced Vit K production by gut flora via ABx
Interrupting the Vit K cycle via acetaminophen (1.5-2g chronically)

30
Q

What is the ABCDEF R of warfarin and its effects?

A

Increased INR = increased bleeding
Amiodarine
Bactrim
Cipro + other fluoroquinolones
Diflucan + other azoles
Erythromycin + other macrolides
Flagyl (Metronidazole)

Decreased INR = decreased bleeding
Rifampin

31
Q

If I want to start a patient on amiodarone but they are on warfarin already, how should I adjust my dosages?

A

I would expect a REDUCTION in my warfarin dosage by up to 50%, because amiodarone INCREASES INR.
(AKA bleeding more bc takes longer to clot)

32
Q

What are some common drug interactions with antiseizure meds? Describe what happens.

A

Lamotrigine + other antiseizures
Lamotrigine = substrate

Carbamazepine = Inducer
Valproic acid = Inhibitor

Lamotrigine + carbamazepine = drug gets metabolized faster, so I need MORE lamotrigine.

Lamotrigine + Valproic acid = drug barely gets metabolized, so I need LESS lamotrigine.

33
Q

What is the effect of a PDE-5 inhibitor and nitrate together?

A

They have additive effects of major vasodilation and consequently severe hypotension.

PDE-5 inhibitors = sildenafil/viagra or tadalafil
Nitrates = Nitroglycerins, isosorbides
Category X interactions.