Lecture 6: Drug Interactions Flashcards
What are the common risk factors associated with drug interactions?
Polypharmacy
Multiple prescribers
Multiple pharmacies
Genetic makeup
Special populations
Drug makeup
What is the definition of a drug interaction?
Modification of the effect of one drug by the prior concomitant administration of another drug.
What are the drug - dietary supplement interactions?
Rx, OTC, illicit substances
St. John’s Wort
Cocaine & antiHTNs
What are the drug - food or drink interactions?
Doxycycline & milk
Metronidazole and alcohol
What are the drug - disease interactions?
Beta blockers & asthma
NSAIDs & heart failure
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.
What are the pharmacodynamic drug interactions?
Additive effects on same receptor or additive effects on different receptors.
Synergistic effects (aminoglycosides + penicillin)
Antagonist blocking agonist effects (Naloxone for opioids)
What are some of the additive interactions pharmacodynamically?
Increased bleeding risk
Anticholinergic toxicity
Nephrotoxicity
QT Prolongation
Serotonergic Agents
Hyperkalemia (increased potassium)
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
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
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
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
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
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)
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 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 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 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 = increased bleeding
Amiodarine
Bactrim
Cipro + other fluoroquinolones
Diflucan + other azoles
Erythromycin + other macrolides
Flagyl (Metronidazole)
Decreased INR = decreased bleeding
Rifampin
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.
