T2 Lecture 6: Drug Interactions Flashcards by Ellie Cheney

What are the common risk factors associated with drug interactions?

Polypharmacy
Multiple prescribers
Multiple pharmacies
Genetic makeup
Special populations
Drug makeup

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What is the definition of a drug interaction?

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

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What are the drug - dietary supplement interactions?

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

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What are the drug - food or drink interactions?

May cause interaction or prevent appropriate absorption
Doxycycline & milk
Metronidazole and alcohol

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What are the drug - disease interactions?

May be helpful in one disease but harmful in another
Beta blockers & asthma
NSAIDs & heart failure

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What are the categories of Drug Interaction Severity?

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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What are the pharmacodynamic drug interactions?

Additive effects on same receptor or additive effects on different receptors.

Synergistic effects: effect of 2 drugs magnified beyond what would be expected (aminoglycosides + penicillin)

Antagonist blocking agonist effects (Naloxone for opioids)

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What are some of the additive interactions pharmacodynamically?

Increased bleeding risk

Anticholinergic toxicity

Nephrotoxicity

QT Prolongation

Serotonergic Agents

Hyperkalemia (increased potassium)

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What drugs can cause increased bleed risk additively?

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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What drugs can cause anticholinergic toxicity additively?

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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Anticholinergic side effects

dry mouth, constipation, urinary retention, bowel obstruction, blurred vision, inc heart rate, dec sweating

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What drugs can cause nephrotoxicity additively?

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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What drugs can cause QT prolongation additively?

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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What drugs can boost serotonin additively?

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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What drugs can cause hyperkalemia additively?

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

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

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

Binding to alpha-1 acid glycoproteins
Binding to albumin

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

Phase I: oxidation, reduction, hydrolysis for inactivation// CYP P450 enzymes
Phase II: glucuronidation, sulfation, methylation for elimination

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

Competition for transport
Change in urinary pH

What are the CYP Inducers?

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

What do CYP inducers do?

What are the CYP inhibitors?

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)

What do CYP inhibitors do?

reduce enzymatic activity and metabolism
inc active drug availability
quick effect

What drugs are 3A4 substrates?

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

What drugs are 2D6 substrates?

Analgesics, Antidepressants/antipsychotics, and others

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

33%, mostly via phase II metabolism. Note: Non-CYP metabolism usually has less drug interactions. Most common are via UDP, NAT, and MAO.

What toxicity can occur via Non-CYP enzyme metabolism?

Isoniazid toxicity

What are some p-gp substrates?

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

What are some p-gp Inhibitors?

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

Why do we use prodrugs?

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

What are the common prodrugs?

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

What are the common narrow therapeutic index drugs?

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)

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

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)

What is the ABCDEF R of warfarin and its effects?

Increased INR (how thick blood is) = increased bleeding **A**miodarine **B**actrim **C**ipro + other fluoroquinolones **D**iflucan + other azoles **E**rythromycin + other macrolides **F**lagyl (Metronidazole) Decreased INR = decreased bleeding **R**ifampin (an inducer)

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

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)

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

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.

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

They have additive effects of major vasodilation and consequently severe hypotension. PDE-5 inhibitors = sildenafil/viagra or tadalafil Nitrates = Nitroglycerins, isosorbides Category X interactions.