Intro-ADR-Part-II Flashcards
What is the Major Challenge in Managing DDI in individual patients?
- Variability in the magnitude of PK/PD changes
- Clinical outcome in individual patients
[Personalized DDI predictions = better managed variability]
What are the appropriate actions to take when possible to reduce the risk from potential DDIs?
- Avoid concomitant administration
- Implement alternative therapeutic strategies
- Take precautionary measures
All of the following are PATIENT factors that influence clinical outcomes of drug interactions EXCEPT? A. Genetics B. Diseases C. Diet/Nutrition D. Dosing Times
D is incorrect
Dosing times are drug factors that contribute to high variability in drug interactions.
[Other patient factors include: Environment, smoking and alcohol]
All of the following are DRUG factors that influence clinical outcomes of drug interactions EXCEPT? A. Dose B. Duration C. Genetics D. Sequence
C. is incorrect
Genetics is a patient factor contributing to high variability.
[Other drug factors include: Dosing time, Route, and Dosage Form]
T/F
Extensive metabolizers of 2D6 will show only a mild change in clearance when a 2D6 inhibitor is added to a drug regimen
False
POOR METABOLIZERS of 2D6 substrates (object drug) will show only a mild change in clearance when a 2D6 inhibitor (precipitant drug) regimen
[example of 2D6 substrate = metoprolol]
Which of the following is/are true of POOR METABILZERS of PRECIPITANT DRUGS (inhibitors or inducers)
A. Concentration of precipitant drug may be higher
B. May show smaller change in clearance of object drug
C. May show larger change in clearance of object drug
D. A & C
E. B & C
A & C are true
Poor metabolizers of precipitant drugs will accumulate the drug and have a large change in clearance of object drug
A patient who is a POOR METABOLIZER for a PRECIPITANT drug involved in a DDI will:
A. Have a larger change in the object drug plasma concentration than that seen in a patient who is a rapid metabolizer of the precipitant drug
B. Be at no risk of harm from the interaction
C. Probably be on large doses of the precipitant drug to get a therapeutic response
D. Probably be on large doses of the object drug to a get a therapeutic response
E. Non of the above are correct
A. is correct!
PMs have a larger change in the object drug plasma concentration than that seen in a patient who is a rapid metabolizer of the precipitant drug
Which of the following is true about EXTENSIVE METABOLIZERS of OBJECT drugs?
A. EMs of object drugs will have a significant increase in concentration when co-administered with an inducer
B. EMs For object drugs will have a significant increase in concentration when co-administered with an inhibitor
C. EMs of object drugs will not be affected by a precipitant drugs
D. None of the above
B is correct
Patients who are EMs for object drug will have a largest magnitude increase when co-administer with an inhibitor
What is the interaction between Diphenhydramine and Metoprolol?
Diphenhydramine is a 2D6 inhibitor that DECREASES clearance of drugs such as metoprolol that are substrates of 2D6. THE EFFECTS ARE SEEN ONLY IN EXTENSIVE METABOLIZERS.
T/F
Potent inhibitors of 2D6 can decrease the analgesic effects of codeine
True
Quinidine is a potent inhibitor of 2D6
[As well as amiodarone, bupropion, fluoxetine, paroxetine]
What is the DDI and Drug-disease interaction between Tocilizumab & simvastatin for RA patients?
RA patients have increased IL-6. This reduces CYP activity & increases exposure of CYP substrates. Tocilizumab may reverse IL-6-induced suppression of CYP3A4 activity. Thus, exposure to simvastatin was significantly REDUCED.
What is the primary difficulty in predicting the effects of fluconazole on warfarin?
Large interpatient variability. Fluconazole can increase the exposure to warfarin and increase the risk of bleeding.
Diphenhydramine inhibits metabolism of which Beta-blocker?
Metoprolol
[EM/PM] patients will be harmed more by the use of an inhibiting drug
EM
This is the process by which 2D6 converts codeine to morphine
O-demethylation
2D6 [PM/EM/UM] get the most morphine out of codeine?
UM
Patients who are PMs for [object/precipitant] drugs may have higher concentration of that drug and may have larger magnitudes of interactions
Precipitant
T/F
Patients who are PMs for PRECIPITANT drugs will not be harmed as much as EM patients for that drug
False
T/F
Patients who are PMs for OBJECT drugs will not be harmed as much as EM patients for that drug
True
MTX is a substrate of BCRP. . PPIs are inhibitors of BCRP. Who is more at risk, a 2C19 EM or PM?
Poor metabolizers (PM) [precipitant drug]
This drug and this class of drugs led to some severe (sometimes fatal) hyperkalemia in some elderly patients?
Spironolactone + ACEI
[most patients had multiple risk factors: renal failure, diabetes, worsening CHF, age > 70, taking other hyperkalemic drugs (NSAIDS)]
What caused the fatalities in the spironolactone/ACEI DDI patients?
Hyperkalemia
What is the take away message from the fluconazole/warfarin study?
High variability!
[Low/High] bioavailability drugs are more dangerous when adding GFJ or another inhibitor?
LOW
What is the OBJECT drug out of mexiletine and tizanidine?
Tizanidine
[Low/High] first pass metabolized drugs are more dangerous when you add a precipitant?
High
