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PCEUT 510 > DDI-Transporters > Flashcards

DDI-Transporters Flashcards

1
Q

Membrane transporters/carriers are located where?

A
  1. Epithelial barrier

2. Endothelial barrier

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2
Q

Why are transporters important?

A

They play a significant role in drug:

  1. absorption
  2. distribution
  3. excretion
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3
Q

Active Solute Transport
Biochemical Characteristics:
1.
2.

A
  1. Move solute against a concentration gradient

2. REQUIES energy

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4
Q

Active Solute Transport
Classification based on driving force mechanism
1.
2.

A
  1. Primary active transporters = generate energy themselves (ATP hydrolysis)
  2. Secondary active transporters = utilize energy stored in voltage and ion gradients generated by a primary active transporter (NA+/K+ ATPase)
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5
Q

Digoxin and _________ was the original transporter-related DDI

A

quinidine

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6
Q

There are two types of secondary active transporters

A
  1. Symporters (Co-transporters)

2. Antiporters ( Exchangers)

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7
Q

A [primary/secondary] active transporter utilizes energy stored in gradients

A

Secondary

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8
Q

A [primary/secondary] active transporter utilizes energy from ATP hydrolysis

A

Primary

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9
Q

These secondary active transporters are also known as co-transporters

A

Symporters

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10
Q

These secondary active transporters are also known as antiporters

A

Exchangers

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11
Q

Pgp, MRPs and BCRP are all part of the ________ superfamily of transporters

A

ATP-Binding Cassette (ABC)

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12
Q

OATP, OCT & MATEs are part of the ________ superfamily of transporters

A

SoLute Carrier (SLC)

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13
Q

This transporter is also known as MDR1

A

Pgp

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14
Q

Pgp mediates the transport of [lipo/hydro]philic [an/cat]ionic drugs?

A

Lipophilic Cationic drugs

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15
Q

Steroids and other cyclic peptides are [acidic/basic/neutral] drugs with ________ ring structures, mediated by_______

A

NEUTRAL rings with BULKY ring structures

Pgp mediated

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16
Q

What 4 tissues is Pgp expressed in?

A
  1. intestine
  2. kidneys
  3. liver
  4. BBB
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17
Q

Pgp has two actions on xenobiotics

A
  1. Guard against entry

2. Promote excretion

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18
Q

Pgp is located on the [Apical/Basolateral] membrane of INTESTINAL mucosal epithelium?

A

APICAL

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19
Q

Pgp is located on the [Apical/Basolateral] membrane of proximal tubular epithelium of KIDNEYS?

A

APICAL

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20
Q

Pgp is located on the [Apical/Basolateral] membrane of hepatocytes in the LIVER?

A

APICAL(canalicular)

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21
Q

Pgp is located on the [Apical/Basolateral] membrane of brain capillary endothelium BBB

A

APICAL

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22
Q

What is the purpose of Pgp in the INTESTINE?

A

DECREASES net absorption due to exsorption and/or secretion

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23
Q

What is the purpose of Pgp in the KIDNEY?

A

FACILITATES renal secretion

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24
Q

What is the purpose of Pgp in the LIVER?

A

FACILITATES biliary secretion

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25
Q

What is the purpose of Pgp in the BBB?

A

PREVENTS drug entry into the brain

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26
Q

T/F

Pgp facilitates biliary secretion

A

True

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27
Q

T/F

Pgp both increases renal secretion AND protects the brain/fetus from drug entry

A

True

28
Q

INHIBITION of INTESTINE Pgp leads to [increase/decrease] of bioavailability?

A

INCREASE

  1. Digoxin-Clarithromycin
  2. Digoxin-Itraconazole
  3. Digoxin-atorvastatin
29
Q

INDUCTION of INTESTINE Pgp leads to [increase/decrease] of bioavailability?

A

DECREASE

  1. Digoxin-rifampin
  2. Digoxin-St. Johns wort
30
Q

Adding clarithromycin to digoxin [increased/decreased] digoxin AUC by 64%

A

Increased

31
Q

Modulation of biliary clearance due Digoxin + quinidine will [induce/inhibit] Pgp transport?

A

INHIBIT

32
Q

Modulation of biliary clearance due to Digoxin + Rifampin will [induce/inhibit] Pgp transport?

A

INDUCE

33
Q

Pgp mediated transport in the Kidney of Digoxin will have [decreased/increased] renal drug clearance when inhibiting agents are used?

A 
DECREASED
Remember: 
Inhibitors; 
quinidine
verapamil
cyclosporine
itraconazole
cyclosporine
34
Q

Brain uptake will [increase/decrease] when loperamide + quinidine are used together due to [inhibition/induction]?

A

INCREASE

INHIBITION

35
Q

__________ in Pgp expression and function in different tissues makes it difficult to predict the outcomes of Pgp based DDIs

A

Multiplicity

36
Q 
All of the following are examples of Multiplicity in Pgp based inhibitory interactions with Digoxin EXCEPT? 
A. quinidine 
B. Clarithromycin 
C. Rifampin
D. Talinolol
A

C is incorrect
Rifampin is an inducer and not one of the examples given
(Ritonavir is the other inhibitor example provided)

37
Q

This drug inhibits intestinal Pgp and increases digoxin F, but does not affect systemic clearance of digoxin

A

Talinolol

38
Q

This Pgp inhibitor didn’t have an effect on renal or biliary inhibition

A

Talinolol

39
Q

This drug increased digoxin AUC and Cmax 1 hour after administration, but lowered it 1 week after administration

A

Rifampin

40
Q

Rifampin [increased/decreased] digoxin AUC and Cmax 1 hour after administration, but [increased/decreased] it 1 week after administration

A

INCREASED

DECREASED

41
Q

The increasing then decreasing effects of Cmax and AUC of Rifampin on Digoxin over a 2 week period are an example of what type of interaction?

A

Biphasic

Rifampin has both Inhibition and induction effects on Pgp transports

42
Q

Most statins prefer this OATP in the liver

A

OATP1B1

43
Q

These two statins are up taken by all three OATP (1B1, 1B3,2B1) liver proteins

A

Fluvastatin

Pravastatin

44
Q

This immunosuppressant is a major OATP inhibitor

A

Cyclosporine

45
Q

This antibiotic is a major OATP inhibitor

A

Rifampin

46
Q

Other than Pgp, cyclosporine and rifampin notably inhibit this family of transporters

A

OATP

47
Q

Interactions between first generation statins and this drug were recognized to result in severe myotoxicity of statins including rhabdomyolysis

A

Cyclosporine

48
Q

This is the most dangerous potential occurrence from the cyclosporine/first gen statin DDI

A

rhabdomyolysis

49
Q

Newer statins are more [lipophilic/hydrophilic] and older statins are more [lipophilic/hydrophilic]

A 
Newer = hydrophilic
Older = lipophilic
50
Q

[Gut Pgp/Hepatic OATP] induction sustained over 24+ hours, while the other dissipated by 12.5 hours in the repaglinide/rifampin interaction

A

Gut Pgp

51
Q

The repaglinide/rifampin interaction showed that induction of 2C8 and 3A4 emerged by __________

A

24 hours

52
Q

[GI/Hepatic/Renal] DDIs are the least common

A

Renal

53
Q

There’s a ~__x limit in magnitude of renal interaction because only the secretory component is affected

A

2

54
Q

There’s a ~2x limit in magnitude of renal interaction because only the _________ component is affected

A

Secretory

55
Q

Renal DDI occurs only for drugs that:

1) Are mainly cleared by the kidneys
2) Undergo extensive active secretion (____ > _______) or active tubular reabsorption

A

CLr > fu*GFR

56
Q

Renal DDI occurs only for drugs that:

1) Are mainly cleared by the kidneys
2) Undergo extensive active _________ (CLr > fu*GFR) or active tubular ____________

A

Secretion

Reabsorption

57
Q

Organic anion Transporters in the Kidney include?

A

OAT

MRP

58
Q

Organic Cation Transports in the Kidney include?

A

OCT2

MATEs

59
Q

OCT2 transporters are on the [APICAL/BASOLATERAL] side?

A

BASOLATERAL

60
Q

MATEs transporters are on the [APICAL/BASOLATERAL] side?

A

APICAL

61
Q

What was the effect on AUC of Metformin + Cimetidine?

A 
AUC = increased
CLr = Decreased
62
Q

Cimetidine inhibits which transporter?

A

MATE

63
Q

Who is the perpetrator in the metformin + cimetidine DDI?

A

Cimetidine

64
Q

Methotrexate DDI involve which transport?

[Pgp/MRP/BCRP]

A

BCRP

65
Q

Who is the precipitating agent involved in the BCRP transporter and Methotrexate?

A

PPI:
Omeprazole
Pantoprazole

66
Q

What is the overall effect of Methotrexate ABC Transporter DDI?

A

Delayed elimination = toxicities

67
Q

What is the overall effect of DDIs between Li + Thiazide diuretics?

A

Increased renal absorption = enhanced lithium retention

PCEUT 510 (12 decks)

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