Drug Interactions Flashcards
Difference between phase I and phase II reactions (metabolic enzymes)
Phase I = oxidation, reduction, hydrolysis
Phase II = terminates the activity of the drug
Phase I provides a reactive functional group for the enzyme to attack during phase II
Rifampin
Inducer of pretty much every CYP enzyme and P-gp pumps
Rifampin and warfarin
Rifampin is an inducer
Induces metabolism of warfarin
Needs up to 300% more warfarin
Amiodarone
CYP2C9 inhibitor
Big inducers
PS PORCS Phenytoin Smoking Phenobarbital Oxcarbazepine Rifampin (and rifabutin, rifapentine) Carbamazepine (and is an auto inducer) St John's Wort
Big Inhibitors
G <3 PACMAN Grapefruit <3 Protease inhibitors (ritonavir) Azole antifungals C - cyclosporine, cimeditine, cobicistat Macrolides (not azithromycin) Amiodarone (and dronedarone) Non-DHP CCBs (diltiazem, verapamil)
Warfarin metabolism
2C9 and 1A2
P-gp inducers
Cabamazepine Dexamethasone Phenobarbital Phenytoin Rifampin St John's Wort Tipranavir
P-gp inhibitors
Anti-infectives (clarithromycin, itraconazole, posaconazole)
Cardiovascular drugs (amiodarone, carvedilol, dronedarone, conivaptan, diltiazem, quinidine, verapamil)
HIV drugs (cobicistat, ritonavir)
HCV drugs (daclatasvir, ledipasvir, paritaprevir, simeprevir)
Others (cyclosporine, flibanserin, ticagrelor)
P-gp substrates
Anticoagulants (apixaban, edoxaban, rivaroxaban, dabigatran) Cardiovascular drugs (carvedilol, digoxin, ranolazine) Immunosuppressants (cyclosporine, sirolimus, tacrolimus) HCV drugs (dasabuvir, paritaprevir, ombitasvir, simeprevir, sofosbuvir) Others (atazanavir, colchicine, dolutegravir, fexofenadine, posaconazole, raltegravir, saxagliptin)
Amiodarone and rivaroxaban
Amiodarone inhibits both CYP3A4 and P-gp, rivaroxaban is a substrate for both of these
Using together would increased rivaroxaban levels and increase bleeding risk
Warfarin and amiodarone
Amiodarone inhibits warfarin metabolism
Decrease dose of warfarin or amiodarone when using both if started initially
If starting warfarin already on amiodarone, decrease warfarin starting dose by 30-50%
Amiodarone and statins
Use lower doses of simvastatin and lovastatin
Amiodarone inhibits CYP3A4, 2C8, 2C9, and 2D6
Digoxin metabolism
Renally eliminated
P-gp substrate
Digoxin and amiodarone
Amiodarone can elevate digoxin concentrations
Tacrolimus and grapefruit juice
Grapefruit juice increases tacrolimus levels
Lamotrigine and valproate
Risk of severe rash with this combination
Monoamine oxidase inhibitors drug interactions
Increased risk of hypertensive crisis if given with other adrenergic medications (pseudoephedrine, phenylephrine, SNRIs, bupropion) and stimulants (amphetamines)
MAO-I’s: phenelzine, isocarboxazid, tranylcypromine, selegiline, rasagiline
Methylene blue and linezolid also have MAO-I activity
Also avoid tyramines - can induce norepinephrine release, which can lead to hypertensive crisis
Serotonergic drugs
SSRIs SNRIS TCAs MAO-I's Buspirone Dextromethorphan Fentanyl Lithium Methadone Mirtazapine St John's Wort Tramadol Trazadone
Serotonin syndrome symptoms
Agitation Rapid HR High fever Excessive sweating Muscle twitching or stiffness N/V/D
Tramadol metabolism
Converted by CYP2D6 to active metabolite
Those on 2D6 inhibitors cannot convert tramadol to its active metabolite
Results in diminished analgesic effect
Drug interactions of immunosuppressants
Tacrolimus and cyclosporine are both 3A4 and P-gp substrates
Sirolimus is just 3A4
Worry about fungal infections treated with azoles (inhibitors) and bacterial infections treated with macrolides (also inhibitors) or rifampin (inducers)
5 G’s that increase bleeding risk
Gingko biloba (no inc in INR) Garlic Ginger Glucosamine Ginseng
