Intro-ADR-Part-II

Question 1

What is the Major Challenge in Managing DDI in individual patients?

Answer 1

1. Variability in the magnitude of PK/PD changes
2. Clinical outcome in individual patients
   [Personalized DDI predictions = better managed variability]

Question 2

What are the appropriate actions to take when possible to reduce the risk from potential DDIs?

Answer 2

1. Avoid concomitant administration
2. Implement alternative therapeutic strategies
3. Take precautionary measures

Question 3

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

Answer 3

D is incorrect
Dosing times are drug factors that contribute to high variability in drug interactions.
[Other patient factors include: Environment, smoking and alcohol]

Question 4

All of the following  are DRUG factors that influence clinical outcomes of drug interactions EXCEPT? 
A. Dose
B. Duration
C. Genetics
D. Sequence

Answer 4

C. is incorrect
Genetics is a patient factor contributing to high variability.

[Other drug factors include: Dosing time, Route, and Dosage Form]

Question 5

T/F

Extensive metabolizers of 2D6 will show only a mild change in clearance when a 2D6 inhibitor is added to a drug regimen

Answer 5

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]

Question 6

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

Answer 6

A & C are true

Poor metabolizers of precipitant drugs will accumulate the drug and have a large change in clearance of object drug

Question 7

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

Answer 7

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

Question 8

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

Answer 8

B is correct

Patients who are EMs for object drug will have a largest magnitude increase when co-administer with an inhibitor

Question 9

What is the interaction between Diphenhydramine and Metoprolol?

Answer 9

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.

Question 10

T/F

Potent inhibitors of 2D6 can decrease the analgesic effects of codeine

Answer 10

True
Quinidine is a potent inhibitor of 2D6
[As well as amiodarone, bupropion, fluoxetine, paroxetine]

Question 11

What is the DDI and Drug-disease interaction between Tocilizumab & simvastatin for RA patients?

Answer 11

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.

Question 12

What is the primary difficulty in predicting the effects of fluconazole on warfarin?

Answer 12

Large interpatient variability. Fluconazole can increase the exposure to warfarin and increase the risk of bleeding.

Question 13

Diphenhydramine inhibits metabolism of which Beta-blocker?

Answer 13

Metoprolol

Question 14

[EM/PM] patients will be harmed more by the use of an inhibiting drug

Answer 14

EM

Question 15

This is the process by which 2D6 converts codeine to morphine

Answer 15

O-demethylation

Question 16

2D6 [PM/EM/UM] get the most morphine out of codeine?

Answer 16

UM

Question 17

Patients who are PMs for [object/precipitant] drugs may have higher concentration of that drug and may have larger magnitudes of interactions

Answer 17

Precipitant

Question 18

T/F

Patients who are PMs for PRECIPITANT drugs will not be harmed as much as EM patients for that drug

Answer 18

False

Question 19

T/F

Patients who are PMs for OBJECT drugs will not be harmed as much as EM patients for that drug

Answer 19

True

Question 20

MTX is a substrate of BCRP. . PPIs are inhibitors of BCRP. Who is more at risk, a 2C19 EM or PM?

Answer 20

Poor metabolizers (PM)
[precipitant drug]

Question 21

This drug and this class of drugs led to some severe (sometimes fatal) hyperkalemia in some elderly patients?

Answer 21

Spironolactone + ACEI
[most patients had multiple risk factors: renal failure, diabetes, worsening CHF, age > 70, taking other hyperkalemic drugs (NSAIDS)]

Question 22

What caused the fatalities in the spironolactone/ACEI DDI patients?

Answer 22

Hyperkalemia

Question 23

What is the take away message from the fluconazole/warfarin study?

Answer 23

High variability!

Question 24

[Low/High] bioavailability drugs are more dangerous when adding GFJ or another inhibitor?

Answer 24

LOW

Question 25

What is the OBJECT drug out of mexiletine and tizanidine?

Answer 25

Tizanidine

Question 26

[Low/High] first pass metabolized drugs are more dangerous when you add a precipitant?

Answer 26

High