Ch 3: Drug Interactions Flashcards
Drugs w/ polyvalent cations or other binding properties
Antacids
Multivitamins
Sucralfate
Bild acid resins
Aluminum
Calcium
Iron
Magnesium
Zinc
Phosphate binders
Drugs w/ polyvalent cations or other binding properties should be separated from
Quinolones
Tetracyclines
Levothyroxine
Oral bisphosphonates
What are the major CYP3A4 inhibitors
Remember G <3 PACMAN
Grapefruit
<3
Protease inhibitors (PI), especially ritonavir (Norvir)
Azole antifungals (fluconazole, itraconazole, ketoconazole, posaconazole (Noxafil), voriconazole, and isavuconazonium (Cresemba))
Cyclosporine, cimetidine (Tagamet), cobicistat
Macrolides (clarithromycin (Biaxin) and erythromycin, but not azithromycin)
Amiodarone (and dronedarone (Multaq))
Non-DHP CCBs (diltiazem and verapamil)
Brand:Generic
Cardizem
diltiazem
Brand:Generic
Neoral
cyclosporine
What are the major CYP3A inducers
Remember SSR COPP
- St. John’s Wort
- Smoking
- Rifampin (and rifabutin, rifapentine)
- Carbamazepine (also an auto-inducer)
- Oxcarbazepine (and eslicarbazepine)
- Phenytoin
- Phenobarbital
Brand:Generic
Dilantin
phenytoin
P-gp
Substrates
Anticoagulants (apixaban, edoxaban, dabigatran, rivaroxaban)
Cardiovascular drugs (digoxin, diltiazem, carvedilol, ranolazine, verapamil)
lmmunosuppressants (cyclosporine, sirolimus, tacrolimus)
HCV drugs (sofosbuvir)
Others (atazanavir, colchicine, dolutegravir, posaconazole, raltegravir, saxagliptin)
P-gp
Inducers
Carbamazepine,
dexamethasone,
phenobarbital,
phenytoin,
rifampin,
St. John’s wort,
tipranavir
P-gp
Inhibitors
Anti-infectives (clarithromycin, itraconazole, posaconazole)
Cardiovascular drugs (amiodarone, carvedilol, conivaptan, diltiazem, dronedarone, quinidine, verapamil)
HIV drugs (cobicistat, ritonavir)
HCV drugs (ledipasvir)
Others (cyclosporine, flibanserin, ticagrelor)
Enterohepatic recycling ↑ _
duration of action
Common Cardiovacular Drug Intxn
Amiodarone + Warfarin
If using warfarin 1st:
↓ warfarin dose 30-50%
Amiodarone inhibits CYP2C9, which metabolizes warfarin
Common Cardiovacular Drug Intxn
Amiodarone + Digoxin
If using digoxin 1st:
↓ digoxin dose 50%
Amiodarone inhibits P-gp, digoxin is a P-gp substrate → ↑ risk of bradycardia
Common Cardiovacular Drug Intxn: Digoxin + Loop Diuretics
What electrolytes do loops effect?
↓ K, Mg, Ca, & Na
Common Cardiovacular Drug Intxn: Digoxin + Loop Diuretics
What ↑ the risk of digoxin toxicity?
↓ K & Mg
↑ Ca
Common Cardiovacular Drug Intxn: Digoxin + Loop Diuretics
Drugs that ↓ HR
Amiodarone
Digoxin
BB
Clonidine
Diltiazem
Verapamil
Additive effects when use together. Monitor HR (normal: 60-100 BPM)
Also: dexmedetomide (Precedex)
Common Cardiovacular Drug Intxn: Statins + CYP3A4
Which statins ↑ levels of CYP3A4 substrates?
Lovastatin
Simvastatin
Atorvastatin
Common Cardiovacular Drug Intxn: Statins + CYP3A4
Which statins are contraindicated w/ strong CYP3A4 inhibitors?
Lovastatin
Simvastatin
Brand:Generic
Altoprev
lovastatin
Common Cardiovacular Drug Intxn
CYP2C9 inhibitors
Azole
Bactrim
Amiodarone
Metronidazole
Common Cardiovacular Drug Intxn
CYP2C9 inducers
rifampin
St. John’s wort
Phenobarbital
Phenytoin
Primidone
Common Cardiovacular Drug Intxn
What do CYP2C9 inhibitors cause warfarin to do?
↑ warfarin levels → ↑ INR & bleeding
Common Cardiovacular Drug Intxn
What do CYP2C9 inducers cause warfarin to do?
↓ warfarin levels → ↓ INR & clotting
Inhibitors ↑ substrate Drugs
Which opiods are metabolizedf by CYP3A4?
Fentanyl
Hydrocodone
Oxycodone
Methadone
Do NOT use w/ CYP3A4 inhibitors
Inhibitors ↑ substrate Drugs
What drugs have specific instruction not to take w/ grapefruit?
amiodarone
simvastatin
lovastatin
nifedipine
tacrolimus
Inhibitors ↑ substrate Drugs
Valproate + Lamotrigine Intxn
Valproate ↓ lamotrigine metabolsim → ↑ risk of skin reactions
Use starter kit w/ lower doses
Inhibitors ↑ substrate Drugs
MAO inhibitors
Isocarboxazid
Phenelzine
Tranylcypromine
Rasagiline
Selegiline
Linezolid
Methylene blue
Inhibitors ↑ substrate Drugs
How long is the washout period for MAO inhibitors?
2 weeks
Inhibitors ↑ substrate Drugs
Which MAO inhibitor is the exception for the normal washout period?
Fluoxetine: 5 weeks
Inhibitors ↑ substrate Drugs
Drugs/Foods that ↑ catecholamines (Epi, NE, DA)
bupropion
SNRIs
TCAs
stimulants
levodopa
tyramine (from food)
Can cause hypertensive crisis
Inhibitors ↑ substrate Drugs
Drugs/Foods that ↑ 5-HT
Antidepressants: SSRIs, SNRIs, TCAs, mirtazapine, trazodone,
Opioids & analgesics: fentanyl, methadone, tramadol
Others: buspirone, lithium, dextromethorphan (high doses), St. John’s wort
Can cause serotonin syndrome
Brand:Generic
Remeron
mirtazapine
Inhibitors ↑ substrate Drugs
CYP2D6 inhibitors
Amiodarone,
fluoxetine,
paroxetine,
fluvoxamine
Inhibitors ↑ substrate Drugs
CYP2D6 substrates
codeine
meperidine
tramdol
tamoxifen
Just some examples
Inhibitors ↑ substrate Drugs
Calcineurin inhibitors should be avoided with?
(Tacrolimus, cyclosporine)
Also mTOR kinase inhibitors (Sirolimus, everolimus)
CYP3A4 & P-gp inhibitors & inducers
Inhibitors: ↓ drug substrate metabolism
Inducers: ↑ risk of transplant rejection
Inducers ↓ substrate Drugs
Antiepileptic drugs CYP inducers
Phenytoin
Phenobarbital
Primidone
Carbamazepine (self inducer)
Oxcarbazepine
Some CYP substrates: Oral contraceptives, other AEDs, carbamazepine