PHRM 835 Exam 2 Transporters Flashcards

1
Q

three major drug transporters to know

A

-P-gp (P-glycoprotein)
-OATP (organic anion transporting protein)
-PEPT1 (peptide transporter 1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

example of efflux transporter

A

P-gp (P-glycoprotein)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

example of uptake transporters (2)

A

-OATP (organic anion transporting protein)
-PEPT1 (peptide transporter 1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

P-gp is an efflux transporter affecting __________ of drugs

A

permeability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

P-gp is also known as ?

A

MDR1 (multi-drug resistance 1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

true or false: inhibition of P-gp in cancer cells is expected to improve anticancer drug efficacy by increasing intracellular drug concentrations

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

P-gp is expressed on the ____ side of tissue

A

apical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

P-gp substrate to know

A

Paclitaxel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

most of the P-gp inhibitors are also substrates of P-gp and capable of _______ inhibiting P-gp function

A

competitively

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

true or false: inhibition of P-gp in brain is expected to increase the penetration of P-gp substrates into brain

A

true

(inc. conc of P-gp substrate into brain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

if you take loperamide with a P-gp inhibitor, would there be more or less metabolite in the brain than if taken without a P-gp inhibitor?

A

more

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

true or false: HIV-associated Neurocognitive Disorders occurs when HIV enters the nervous system and impacts the health of nerve cells. Combining HIV protease inhibitors (P-gp substrates) with P-gp inhibitors will likely increase the brain distribution of anti-HIV drugs

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

P-gp in the liver is expressed where?

A

at bile canaliculus

(bile canalicular membrane of the liver)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

true or false: combining paclitaxel with a P-gp inhibitor will likely decrease biliary excretion of paclitaxel

A

true

(drug is biliary excreted)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

true or false: biliary excretion of paclitaxel is its major elimination route. Combining paclitaxel with a P-gp inhibitor will likely decrease paclitaxel elimination from the body and increase systemic drug concentration

A

true

(leads to accumulation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

true or false: there is no P-gp in the placenta

A

false

(P-gp is part of fetal protection system)

17
Q

true or false: P-gp inhibitors will likely increase the passage of P-gp substrates across placenta, leading to increased fetal drug levels

A

true

18
Q

two xenobiotic substrates to know for OATP superfamily

A

-fexofenadine
-statins

19
Q

endogenous compounds for OATP superfamily (3)

A

bilirubin
bile salts
steroid hormone metabolites (e.g. estradiol glucuronide)

20
Q

true or false: OATP1B1 in liver pumps drug out of the hepatocyte

A

false

(pumps drug into hepatocyte)

21
Q

true or false: OATP1B1 inhibition will likely decrease the intrahepatic concentration of OATP1B1 substrates

A

true

22
Q

life threatening side effect of statins

A

rhabdomyolysis

23
Q

cerivastatin was withdrawn in 2001 due to increased myopathy. Risks were higher in patients using fibrates, mainly which drug?

a. fenofibrate
b. gemfibrozil
c. clofibrate
d. bezafibrate

A

b. gemfibrozil

(it is a OATP1B1 inhibitor)

24
Q

cerivastatin was withdrawn in 2001 due to increased myopathy. Risks were higher in patients using fibrates, mainly which drug?

a. fenofibrate
b. gemfibrozil
c. clofibrate
d. bezafibrate

A

b. gemfibrozil

(this lowers cholesterol and is a OATP1B1 inhibitor)

25
Q

what is the significance of OATP1B1 CC genotype vs the TC or TT genotype?

A

CC genotype is linked with a greater incidence of side effects and myopathy

26
Q

fexofenadine is a substrate of which OATPs? (2)

A

OATP1A2 and OATP2B1

27
Q

true or false: grapefruit juice inhibits OATP

A

true

28
Q

PEPT1 (peptide transporter 1) is found in which organ?

A

small intestine

29
Q

substrates for PEPT1 (peptide transporter 1) (2)

A

-dipeptides and tripeptides
-beta-Lactam antibiotics

(peptides and antibiotics)

30
Q

PEPT1 can be used to improve ____ absorption of drugs

A

oral

31
Q

PEPT1 example from class

A

valacyclovir; it is a prodrug and has higher oral absorption. When administered at the same dose, valacyclovir leads to higher systemic exposure to acyclovir

32
Q

Which of the following is NOT the expected biological consequence of a P-gp substrate drug when it is co-administered with a P-gp inhibitor?

a. inc brain distribution
b. inc biliary excretion
c. inc intestinal absorption
d. inc drug transfer to fetus

A

b. inc biliary excretion

33
Q

which one of the following transporters is responsible for increased absorption of valacyclovir as compared to acyclovir?

a. P-gp
b. OATP1B1
c. PEPT1
d. OCT1

A

c. PEPT1

34
Q

genetic polymorphisms of OATP1B1 that are associated with nonfunctional transporter activity would lead to:

a. increased hepatotoxicity of statins
b. decreased efficacy of statins
c. decreased myopathy of statins
d. none of the above

A

b. decreased efficacy of statins