Drug Interactions Flashcards
(19 cards)
What are 4 drug classes that polyvalent cations should be separated from?
polyvalent cations or drugs with other binding properties (antacids, MVIs, sucralfate, bile acid resins, aluminum, calcium, iron, magnesium, zinc, phosphate binders) should be separated from:
- quinolones
- tetracyclines
- levothyroxine
- oral bisphosphonates
What is the significance of codeine being a prodrug?
Codeine is a prodrug of morphine, activated by CYP2D6.
If given to an ultrarapid metabolizer of CYP2D6, it can lead to toxicity.
If given to a poor metabolizer of CYP2D6, the patient may not achieve adequate pain control.
What are the common drugs that are CYP inhibitors? (G <3 PACMAN)
G - grapefruit
P - protease inhibitors (PIs); especially ritonavir
A - azole antifungals
C - cyclosporine, cobicistat
M - macrolides (clarithromycin and erythromycin, NOT azithromycin)
A - amiodarone (and dronedarone)
N - non-DHP CCBs (diltiazem, verapamil)
What are the common drugs that are CYP inducers? (PS PORCS)
P - phenytoin
S - smoking
P - phenobarbital
O - oxcarbazepine
R - rifampin (and rifabutin, rifapentine)
C - carbamazepine
S - st. John’s wort
What is “lag time” for enzyme induction?
Induction usually requires additional enzyme production, so the full effect of a CYP inducer may take up to 4 weeks. When the inducer is stopped, it could take 2-4 weeks for the induction effects to disappear completely, as the excess enzymes will degrade based on their half lives.
What 5 drug classes are common pgp substrates? What drugs are inducers and inhibitors?
Substrates:
- anticoagulants: apixaban, rivaroxaban
- cardiovascular drugs: digoxin, diltiazem, verapamil
- HCV drugs: sofosbuvir
- immunosuppressants: cyclosporine, tacrolimus
Inducers: lots of overlap with the CYP inducers
- carbamazepine
- phenobarbital
- phenytoin
- rifampin
- st. john’s wort
Inhibitors: lots of these are also substrates
- anti-infectives (clarithromycin, itraconazole, posaconazole)
- cardiovascular drugs (amiodarone, diltiazem, verapamil)
- HCV drugs (ledipasvir)
- HIV drugs (cobicistat, ritonavir)
- others (cyclosporine)
What is significant about using amiodarone and warfarin?
amiodarone inhibits CYP2C9, which metabolizes warfarin, so this increases the concentration of warfarin.
if using amiodarone 1st and adding warfarin: start warfarin at lower dose of ≤ 5mg.
if using warfarin 1st and adding amiodarone: decrease warfarin by 30-50%
What is significant about using amiodarone and digoxin?
amiodarone inhibits pgp and digoxin is a pgp substrate, which increases digoxin toxicity (inc. risk of bradycardia)
if using digoxin 1st and adding amiodarone: decrease the oral digoxin dose by 50%
when taking both amiodarone and digoxin, be cautious of other drugs that can decrease HR (beta-blockers, clonidine, diltiazem, verapamil)
What is significant about using digoxin and loop diuretics?
loop diuretics decrease potassium, magnesium, calcium, and sodium. Digoxin toxicity risk is increased with decreased potassium and magnesium levels and increases calcium levels.
Digoxin is also renally excreted. Loop diuretics can worsen renal impairment, which can exacerbate toxicity.
if taking digoxin and a loop diuretic, monitor electrolytes and correct PRN. Also monitor renal function and decrease digoxin dose PRN.
What is significant about using valproate and lamotrigine?
valproate is an inhibit of lamotrigine metabolism, which can increase the risk of serious skin reactions with lamotrigine, including SJS/TEN.
Use the lower lamotrigine starting dose kit with valproate and titrate very carefully.
Which drugs are monoamine oxidase inhibitors? What drugs/foods cannot be used in MAO-is?
MAO-is: isocarboxazid, phenelzine, tranylcypromine, rasagiline, selegiline, linezolid, methylene blue
Any food/drug that increases epinephrine, norepinephrine, or dopamine must be avoided. Also drugs that increase serotonin must be avoided.
- foods: tyramine rich foods (aged cheeses, air-dried meats, sauerkraut)
Need 2 week washout period when switching between drugs with MAO inhibition or serotonergic properties (5 weeks with fluoxetine)
What is significant about using CYP3A4 or pgp inhibitors with calcineurin inhibitors or mTOR kinase inhibitors?
calcineurin inhibitors (CNIs, tacrolimus, cyclosporine) and mTOR kinase inhibitors (sirolimus, everolimus) are CYP3A4 and pgp substates. Using them with inhibitors of CYP3A4 or pgp would increase toxicity.
Avoid using these together
Which opioids are CYP3A4 substrates?
fentanyl, hydrocodone, oxycodone, and methadone are CYP3A4 substrates.
How does current smokers/quitting smoking effect some antipsychotics/antidepressants/hypnotics/anziolytics/caffeine/theophylline/warfarin?
Current smoking: CYP1A2 substrates with have LOWER levels
Smokers who quit: concentrations of CYP1A2 substrates will increase
What are the 5Gs of natural products that have bleeding risk?
Garlic
Ginger
Ginkgo biloba
Ginseng
Glucosamine
Which antidepressants, antipsychotics, antiemetics, and oncology meds have QT prolongation risk?
antidepressants: SSRIs, highest risk with citalopram and escitalopram, TCAs, also mirtazapine, trazodone, and venlafaxine
- do not exceed citalopram 40mg QD or 20mg QD in pt > 60 yo
- do not exceed escitalopram 20mg QD or 10mg in pt > 60yo
(sertraline is the safeat)
antipsychotics: first-gen (haloperidol, thioridazine), second-gen highest risk if ziprasidone
antiemetics: 5-HT3 antagonists (ex. ondansetron)
oncology meds: androgen deprivation therapy (leuprolide), tyrosine kinase inhibitors (nilotinib), arsenic trioxide
What 5 drug classes have ototoxicity risk?
- aminoglycosides
- cisplatin
- loop diuretics (furosemide, bumetanide, ethacrynic acid)
- salicylates (ASA, salsalate, magnesium salicylate)
- vancomycin
What 6 drug classes have nephrotoxicity risk?
- anti-infectives (aminoglycosides, vancomycin, amphotericin B, polymyxins)
- cisplatin -> can use amifostine to protect kidneys
- calcineurin inhibitors (cyclosporine, tacrolimus)
- loop diuretics
- NSAIDs
- radiographic-contrast dye
What is the significance on using PDE-5 inhibitors with CYP3A4 inhibitors?
CYP3A4 inhibitors decrease PDE-5 inhibitors metabolism, which increases risk of side effects, including dizziness, flushing, headache, falls/injury.
