Transporters Flashcards
example of efflux transporter
P-glycoprotein
uptake transporters (2)
- OATP
- PEPT1
uptake transporters
- OATP (organic ___ trasporting protein)
- PEPT1 (____ transporter 1)
- anionic
- peptide
P-glycoprotein
- Efflux transporter affecting ___ of drugs
- leads to ___ to certain drugs
- also called ___
- permeability
- resisitance
- MDR1
T or F: Inhibition of P-gp in cancer cell is expected to improve anticancer drug efficacy by increasing intracellular drug concentrations
True
P-gp tissue distribution
P-gp is expressed on the ___ side
apical
BBB
- brain capillaries have ___ junctions, not ___.
- brain capillaries are surrounded by ___.
- ___ mediated transport used
- tight, pores
- astrocyte processes
- carrier
P-glycoprotein (P-gp) inhibitors
Most P-gp inhibitors are also substrates of P-gp and capable of ___ inhibiting P-gp function.
competitively
T or F: Inhibition of P-gp in brain is expected to increase the penetration of P-gp substrates into brain
True
T or F: HIV-associated Neurocognitive Disorders occurs when HIV enters the nervous system and impacts
the health of nerve cell. Combining HIV protease inhibitors (P-gp substrates) with P-gp inhibitors will likely increase
brain distribution of anti-HIV drugs.
True
- portal vein to central vein (traveling ___)
- Bile canaliculus to bile duct (traveling ___)
- in
- outward
P-gp in liver
- Expressed at the bile ___ membrane of the liver
- P-gp substrates are subject to ___ excretion
- canalicular
- biliary
T or F: Combining paclitaxel with a P-gp inhibitor will likely decrease biliary excretion of paclitaxel.
true
T or F: 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
true
T or F: P-gp inhibitors will likely increase the passage of P-gp substrates across placenta, leading to increased fetal drug levels
true
OATP Superfamily
- > ___ members with at least ___ OATPs expressed in humans
- type of ___ transporters
- Substrates are ___ compounds such as ___, ___, and ___
- Xenobiotics: ___ and ___
- 300, 11
- uptake
- endogenous, bilirubin, bile salts, and steroid hormone
- fexofenadine, statin
T or F: OATP1B1 inhibition will likely decrease the intrahepatic concentration OATP1B1 substrates
true
Statins and OATP1B1
- statins inhibit ___ reductase in the ___
- substrate of ___
- life threatening side effect: ___
- Risks were higher in patients using fibrates, mainly ___ (an inhibitor), and in patients using the highest dose of cerivastatin
cerivastatin was discontinued in 2001
- HMG-CoA
- OATP1B1
- rhabdomyolysis
- gemfibrozil
Statins and OATP1B1
When OATP1B1 is inhibited
* statin hepatic concentration ___
* statin plasma concentration ___
* statin myopathy ___
* ___ efficacy
* ___ side effects
- decreased
- increased
- increased
- lower
- increased
OATP1B1 genetic polymorphisms and statins
the ___ genotype is more likely to have side effects
CC
___ juice inhibits OATP
Grapefruit
PEPT1 (peptide transporter 1)
- A peptide transporter in the ___
- uptake transporter
- substrates: ___, ___, and ___
- utilized to improve ___ absorption of drugs
- small intestine
- dipeptides, tripeptides, and β-Lactam
- oral
- Acyclovir absorption ___
- Valacyclovir (prodrug) absorption ___
- 20%
- complete
When administered at the same dose,
___ leads to higher systemic
exposure to ___
- valacyclovir
- acyclovir
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?
- Increased brain distribution
- Increased biliary excretion
- Increased intestinal absorption
- Increased drug transfer to fetus
Increased biliary excretion
Which one of the following transporters is responsible for increased absorption of valacyclovir as compared to acyclovir?
- P-gp
- OATP1B1
- PEPT1
- OCT1
PEPT1
Which one of the following transporters is responsible for hepatic uptake of statins?
* P-gp
* OATP1B1
* PEPT1
* OCT1
OATP1B1
Genetic polymorphisms of OATP1B1 that are associated with nonfunctional transporter activity would lead to
- Increased hepatotoxicity of statins
- Decreased efficacy of statins
- Decreased myopathy of statins
- None of the above
Decreased efficacy of statins
