Drug Interactions Flashcards
phase 1 reactions
oxidation, reduction, hydrolysis
phase 2 reactions
generally terminates the activity of the drug
Enzyme metabolism for elimination through the kidneys - the kidneys the drug to be more….
hydrophilic
warfarin is metabolized by…and converts them into…
CYP 2C9, inactive metabolites
inducers
increase the level/activity of the metabolizing enzyme that decreases the amount of active drug in the system– lowers the blood levels of the substrate…most of the time - except for with prodrugs (bioactivation)
Rifampin
one of the strongest induces of many enzymes - (1A2, 2C8, 2C9, 2C19, 3A4 and P-glycoprotein pump)
A patient is taking warfarin and is prescribed Rifampin…what needs to happen
the dose of warfarin needs to be increased by 100-300% due to 2C9 induction
inhibitors
inhibit the activity of the enzymes - less drug metabolism ….. potential drug toxicity
inhibitors
inhibit the activity of the enzymes - less drug metabolism ….. potential drug toxicity
patient is prescribed warfarin and amiodarone….what is the result
amiodarone is a 2C9 inhibitor…inhibiting metabolism of warfarin and increasing serum levels - decrease warfarin dose by 30-50%
Common drug classes that use the 2D6 system
pain and psychiatric drugs
explain codeine’s metabolism
converted to it’s active form (morphine) using 2D6 enzymes. patients who have less 2D6 activity will be sub-therapeutic, can also have ultra rapid metabolizers that can cause extreme overdose for the patient and potentially fatal results
explain the drug interaction between paroxetine and codiene
paroxetine inhibits 2D6 –> a need for a higher codeine dose to have desired effect
inhibition lag time
inhibition is fast (at most takes days for effect) and ends quickly upon inhibitor discontinuation
induction lag time
induction requires additional enzyme production, this takes time…full effect may not be present for up to 2 weeks
discontinuation of an inducer..what do you do
it will take 2-4 weeks for the induction to disappear completely - enzymes must die off based on their half life.
strong inducers
> 80% decrease in AUC
strong inhibitors
> 5 fold increase in AUC
moderate inducers
50-80% decrease in AUC
moderate inhibitors
> 2 but
weak inducers
20-50% decrease in AUC
weak inhibitors
> 1 fold but
P-glycoproteins (P-gp) - explain their function
efflux proteins that pump drug back into the gut to exit the body
P-gp inducers cause
creastion of more p-gp pumps and drug levels decrease
P-gp inhibitors cause
inhibition of pgp pumps and increased drug levels
Strong P-gp inducers
rifampin, avasimibe, carbamazepine, phenytoin, st. john’s wort, tipranavir/ritonavir
strong p-gp inhibitors
itraconazole/ketoconazole, verapamil, ritonavir, lopinavir/ritonavir, indinavir/ritonavir, conivaptan, clarithromycin, erithromycin, amiodarone, quinidine
p-gp substrates
aliskiren, colchicine, dabigatran, cyclosporin, digoxin, fexofenadine, posaconazole, fanolazine, rivaroxaban, saxagliptin, tarcolimus
amiodarone drug interactions
digoxin, warfarin, quinidine, procainamide (decrease dose by 30-50%), use lower doses of simvastatin, lovastatin, and adorvastatin.
digoxin drug interactions
level increases with decreased renal function or hypokalemia, amiodarone (drug level will increase). concern with drugs that lower heart rate - diltiazem and verapamil, beta blockers, amiodarone, dexmedetomidine, clonidine, and opioids
organophosphate poisoning
bradycardia is one s symptom (occurs most commonly with farm workers d/t pesticide exposure)
drugs you should avoid grapefruit juice with
simvastatin, lovastatin, atorvastatin, CCB’s (this will cause increased drug concentration), rivaroxaban/ticagrelor (increased bleeding risk), qt prolongers - lurasidone, quinidine, citalopram etc (risk of torsades). not a gut interaction problem this is a drug metabolizing enzyme inactivation problem
lamotrigine drug interactions
valproate (increases risk for severe skin rash) any lam inhibitor will require a lower dose titration, inducers will require a higher dose (impair seizure control)
MAOI drug interactions
can cause serotonin syndrome and hypertensive crisis - monoamines will reduce metabolism with maoi’s - dopamine, epinephrine, norepi, serotonin and tyramine. DO NOT USE MAOIS with epi and analogies (pseudophedrine etc), bupropion, buspirone, linezolid, lithium, meperidine, SSRIs, SNRIs, tcas, TRAMADOL, LEVADOPA, MIRAZAPINE, DEXTROMETHORPHAN, CYCLOBENZAPRINE, TRIPTANS, ST JOHNS WORT, PROCARBAZINE, LORCASERIN
what happens within you take tramadol or hydrocodone with a 2d6 inhibitor
tramadol - decreased active drug in the body bc prodrug activation is inhibited
hydcodone - will have increased drug in the system - more chance of resp depression etc
hydrocodone, fentanyl, oxycodone and methadone are primarily metabolized by:
3A4 - AVOID 3A4 INHIBITORS WITH THESE DRUGS AND WATCH FOR SUBTHERAPEUTIC RESPONSES WITH INDUCERS
PDE5-INHIBITORS DRUG INTERACTIONS
ADDITIVE HYPOTENSION/DIZZINESS HEADACHE ETC WITH ALPHA BLOCKERS FOR PROSTATE ENLARGEMENT
