Exam Review--Things to Know! Flashcards
This is still being worked on!!! (97 cards)
1
Q
Object/Victim
[definition]
A
The drug that is BEING AFFECTED by the interaction
usually the Substrate for an enzyme
2
Q
Precipitant/Perpetrator
[definition]
A
The drug CAUSING the interaction
3
Q
What are the 6 factors influencing interaction outcomes: Object Drug?
A
- Narrow therapeutic range
- Pre-interaction drug concentration
- High first-pass metabolism
- Genetics-Enzyme & Transporter
- Alternative elimination pathways
- Disease states
4
Q
What are the 4 factors influencing outcomes: Precipitant drug?
A
- Dose or concentration
- Genetics- enzyme & transporter
- Route and time of administration
- Order of administration
5
Q
What are the 6 PATIENT FACTORS that create HIGH VARIABILITY in drug interaction outcomes?
A
- Genetics
- Diseases
- Diet/Nutrition
- Environment
- Smoking
- Alcohol
6
Q
What are the 6 DRUG FACTORS that create HIGH VARIABILITY in drug interaction outcomes?
A
- Dose
- Duration
- Dosing time
- Sequence
- Route
- Dosage Form
7
Q
2D6 DDI
Diphenhydramine + Metoprolol
Who is the Perpetrator/Precipitant?
A
Diphenhydramine
8
Q
2D6 DDI
Diphenhydramine + Metoprolol
Who is the Object/Victim?
A
Metoprolol
9
Q
2D6 DDI
Quinidine + Codeine
Who is the Perpetrator/Precipitant?
A
Quinidine
10
Q
2D6 DDI
Diphenhydramine + Codeine
Who is the Object/Victim?
A
Codeine
11
Q
Metoprolol is a
[Substrate/Inhibitor] of 2D6
A
Substrate
12
Q
Codeine is a
[Substrate/Inhibitor] of 2D6
A
Substrate
13
Q
Diphenhydramine is a
[Substrate/Inhibitor] of 2D6
A
Inhibitor
14
Q
Quinidine is a
[Substrate/Inhibitor] of 2D6
A
Inhibitor
15
Q
2C19 DDI
Fluvoxamine + Omeprazole
Who is the Perpetrator/Precipitant?
A
Fluvoxamine
16
Q
2C19 DDI
Fluvoxamine + Omeprazole
Who is the Object/Victim?
A
Omeprazole
17
Q
Fluvoxamine is a
[Substrate/Inhibitor] of 2C19
A
Inhibitor
18
Q
Omeprazole is a
[Substrate/Inhibitor] of 2C19
A
Substrate
19
Q
1A2 DDI
Fluvoxamine + Theophylline
Who is the Perpetrator/Precipitant?
A
Fluvoxamine
20
Q
1A2 DDI
Fluvoxamine + Theophylline
Who is the Object/Victim?
A
Theophylline
21
Q
Fluvoxamine is a
[Substrate/Inhibitor] of 1A2
A
inhibitor
22
Q
Theophylline is a
[Substrate/Inhibitor] of 1A2
A
Substrate
23
Q
[PM/EM] for OBJECT drug will NOT be affected by precipitant drugs( inhibitors/inducers)
A
PM
24
Q
[PM/EM] for PRECIPITANT drug may have HIGHER concentrations of precipitant drug and LARGER magnitude of change in OBJECT drug CLEARANCE
A
PM
25
[PM/EM] for OBJECT drug will LARGEST magnitude of INCREASE when co-administered with an INHIBITOR
EM
26
[PM/EM] for PRECIPITANT drug may have LOWER magnitude effect on OBEJCT drug CLEARANCE
EM
27
Grapefruit Juice is a
| [Substrate/inhibitor] of 3A4
Inhibitor
28
Verapamil is a
| [Substrate/inhibitor] of 3A4
Inhibitor
29
Itraconazole is a
| [Substrate/inhibitor] of 3A4
Inhibitor
30
Ketoconazole is a
| [Substrate/inhibitor] of 3A4
Inhibitor
31
Clarithromycin is a
| [Substrate/inhibitor] of 3A4
Inhibitor
32
Rifampin is a
| [Substrate/inducer] of 3A4
Inducer
33
If a drug is an inhibitor or inducer of 3A4 it is a
| [perpetrator/victim]
PERPETRATOR!
34
in patients with Rheumatoid arthritis what is the inflammatory cytokine that is elevated and affects regulation of CYP3A4?
IL-6
35
The 2 DDI parameters that we are most concerned with are?
1. Cmax
| 2. AUC
36
Toxicities are usually associated with [victim/perpetrator] drugs
Victim/object drugs
37
Do PPIs [increase/decrease] solubility?
Decrease
38
IL-6 is elevated in what disease state?
| What role does the elevation of IL-6 play on CYP3A4 and Simvastatin AUC?
Rheumatoid arthritis
Suppresses CYP3A4,
Decreasing CL of Simvastatin Causing increased AUC
39
What effect does and IL-6 antagonist used for RA treatment have on Simvastatin?
IL-6 antagonism decrease IL-6 levels in the body
| Decreasing CYP3A4 suppression = increased CL and Decreased AUC & Cmax for Simvastatin
40
What 2 drugs produce STRONG anticholinergic side effects?
| What is the side effect?
1. Diphenhydramine (H1-antagonist)
2. Amitriptyline( TCA)
DECREASE GI motility
41
How does SLOW GI motility affect bioavailability?
Slow motility = increased residence time = increase extent of absorption= INCREASED bioavailability
42
Increased gastric pH leads to:
[increased/Decreased] ionization of BASIC drugs, which [slows/promotes] dissolution and [reduces/accelerates] BIOAVAILIBILITY?
DECREASED ionization
SLOWS dissolution
REDUCES bioavailability
ex:
Itraconazole-antacid
43
Increased gastric pH leads to:
[increased/Decreased] ionization of ACIDIC drugs, which [slows/promotes] dissolution and [reduces/accelerates] ABSORPTION?
INCREASED ionization
PROMOTES dissolution
ACCELERATES absorption
ex: Sulfonylurea antidiabetic drugs
44
What 3 POORLY SOLUBLE, BASIC drug classes are victims of PPI's elevation of gastric pH?
```
1. antifungals
[ketoconazole, itraconazole]
2. tyrosine kinase inhibitors
3. protease inhibitors
[indinavir, atazanavir]
```
45
Itraconazole + Omeprazole DDI who is the [victim/object]?
| How are they affected?
Itraconazole
Decreased AUC/bioavailability
46
Itraconazole + Omeprazole DDI whos is the [perpetrator/precipitant]?
Omeprazole
47
Why is FLUCONAZOLE NOT affected by increased gastric pH and not a concern when used with PPIs?
It is SOLUBLE and NOT very BASIC
48
Tyrosine Kinase Inhibitors + PPIs DDI who is the [victim/object]?
How are they affected?
Tyrosine Kinase Inhibitors [all end in TINIB]
Decreased Cmax and AUC
49
The reduction of Ketoconazole absorption by omeprazole can be reversed by what?
1. Drinking with Coca-Cola!!
| 2. Changing to formulation to solution
50
What role does Coca-Cola play in the DDI between azole antifungals and PPIs?
It reverses the effects of the PPI due to its acidity.
| increasing the AUC of azole antifungals in the presence of PPIs.
51
What affect does dietary fat have on fat-soluble drugs?
INCREASES solubility
52
Orlistat prevents the break down of dietary fat because it is a ___________ inhibitor.
Pancreatic LIPASE inhibitor
53
Orlistat [reduces/increases] absorption of Fat-soluble drugs?
REDUCES absorption
54
```
All of the following are Fat-soluble drugs EXCEPT?
A. Cylosporine
B. Atenolol
C. Amiodarone
D. Levothyroxine
```
B is incorrect, atenolol is water-soluble
55
Orlistat + Cyclosporine
| who is the [victim/object]?
Cyclosporine
| Fat-soluble
56
Orlistat + amiodarone
| who is the [victim/object]?
amiodarone
| Fat-soluble
57
Orlistat + levothyroxine
| who is the [victim/object]?
levothyroxine
| Fat-soluble
58
What effect do antacids have on drug absorption?
SLOWS down rate of absorption of lumen
59
Aluminum containing antacids + levothyroxine DDI who is the[victim/object]?
What effect does this have on bioavailability?
Levothyroxine
DECREASES bioavailability
60
What is the concern with antacid metal ions and antibiotics?
antibiotics CHELATE to Al3+ and Mg2+ containing antacids & form NON-absorbable complexes = SEVERE bioavailability problems
61
Aluminum containing antacids + ciprofloxacin DDI who is the[victim/object]?
What effect does this have on bioavailability?
Ciprofloxacin
DECREASES bioavailability
62
How does Al3+ effect GI motility?
Slows motility
63
How does Mg2+ effect GI motility?
Accelerates motility
64
T/F
Sevelamer is a phosphate binder used to treat increased phosphate in ESRD. It can interfere with the oral absorption of Acidic drugs
True
| Sevelamer is an ANION exchange resin
negatively charged drugs
65
What 3 drugs will Sevelamer interfere with oral absorption?
1. digoxin
2. warfarin
3. ciprofloxacin
66
Estrogen Containing OC + antibiotic DDI is due to what?
Bacteria responsible for OC metabolism >> metabolites enter enterohepatic circulation
Antibiotics kill bacteria >> NO enterohepatic circulation
67
Sulfasalazine undergoes AZO-reduction by gut flora, ampicillin has what effect on the efficacy of this prodrug?
Ampicillin wipes out flora responsible for azo-reduction
DECREASING efficacy of Sulfasalazine in the treatment of IBS
(Prodrug activation is decreased)
68
Primary active transporters
| [definition]
Generate energy themselves (ATP hydrolysis)
69
Pgp is what type of membrane transporter?
Primary active transporter
70
Secondary active transporters
| [definition]
Utilizes energy stored in voltage and ion gradients generated by a primary active transporter (Na+/K+ ATPase)
71
T/F
| Renal OAT is an example of a primary active transporter that relies on the maintenance of Na+ gradient by Na/K/ATPase
False
| Primary does NOT use energy stored by a gradient!
72
OATs are what kind of transporter?
Secondary active transporter driven by ion gradient
73
What does Ki mean?
Binding affinity/potency of the inhibitor
| Small Ki = strong binding affinity of inhibitor
74
Pgp mediated transport in the intestine is on the [apical/basolateral] side
Apical
75
Pgp mediated transport in the kidney is on the [apical/basolateral] side?
Apical
76
Pgp mediated transport in the Liver is on the [Apical/basolateral] side?
Apical
77
Pgp mediated transport in BBB is on the [apical/basolateral] side?
Apical
78
Who is the object/victim drug in Pgp DDIs?
Digoxin
79
Who is the precipitant/perpetrator drug in Pgp DDIs?
Any Pgp Inhibitor/inducer
80
There are two drugs that have dual effects in Pgp DDIs depending on dosing regimen, what are they?
1. rifampin
| 2. ritonavir
81
Pgp DDI
Digoxin + clarithromycin
Who is the [precipitant/perpetrator]?
What is the effect?
Clarithromycin via
inhibition
INCREASED bioavailability of DIGOXIN
82
Pgp DDI
Digoxin + itraconazole
Who is the [precipitant/perpetrator]?
What is the effect?
itraconazole via
inhibition
INCREASED bioavailability of DIGOXIN
83
Pgp DDI
Digoxin + atorvastatin
Who is the [precipitant/perpetrator]?
What is the effect?
atorvastatin via
inhibition
INCREASED bioavailability of DIGOXIN
84
Pgp DDI
Digoxin + rifampin
Who is the [precipitant/perpetrator]?
What is the effect?
Rifampin via
induction
DECREASED bioavailability of DIGOXIN
85
Pgp DDI
Digoxin + quinidine
Who is the [precipitant/perpetrator]?
quinidine
| inhibition
86
Pgp DDI
Digoxin + verapamil
Who is the [precipitant/perpetrator]?
Verapamil
| inhibition
87
Pgp DDI
Digoxin + cyclosporine
Who is the [precipitant/perpetrator]?
Cyclosporine
| inhibition
88
Rifampin inhibits which OATP in the liver in the Biphasic DDI seen with REPAGLINIDE?
OATP1B1
89
What is a dosing strategy to overcome the biphasic DDI of Rifampin + Repaglinide?
1. To minimize powerful inductive effect = give rifampin in the morning
2. Give Repaglinide dosing before each meal through out the day while inhibition is present
3. be aware of full emergency of inductive effect when rifampin is discontinued
4. Close monitoring
90
The OCT2 transporter is located on the [apical/basolateral] side of the renal tubule?
Basolateral
91
The MATE2 transporter is located on the [apical/basolateral] side of the renal tubule?
Apical
92
Cimetidine + Metformin DDI
| Who is the [perpetrator/precipitant]?
Cimetidine
93
Cimetidine + Metformin DDI who is the [object/victim]?
Metformin
94
Cimetidine + Metformin DDI what is it?
Cimetidine INHIBITS efflux of MATE at apical membrane of renal tubule inhibiting Cl of Metformin = INCREASED AUC
95
Methotrexate + PPI DDI?
| What is the interaction & effect?
PPI inhibits BCRP at apical membrane in KINDEYS = DECREASED elimination of METHOTREXATE = increased risk of toxicities
96
[Li] is often elevated in Pts receiving concomitant thiazide because?
Increased renal reabsorption of LI results in the DECREASED CL of Li = precipitate retention of LI & Toxicities
97
Li + thiazide DDI
| Who is the [perpetrator/precipitant]
Thiazide
