PHRM 835 Exam 2 Transporters Flashcards
three major drug transporters to know
-P-gp (P-glycoprotein)
-OATP (organic anion transporting protein)
-PEPT1 (peptide transporter 1)
example of efflux transporter
P-gp (P-glycoprotein)
example of uptake transporters (2)
-OATP (organic anion transporting protein)
-PEPT1 (peptide transporter 1)
P-gp is an efflux transporter affecting __________ of drugs
permeability
P-gp is also known as ?
MDR1 (multi-drug resistance 1)
true or false: inhibition of P-gp in cancer cells is expected to improve anticancer drug efficacy by increasing intracellular drug concentrations
true
P-gp is expressed on the ____ side of tissue
apical
P-gp substrate to know
Paclitaxel
most of the P-gp inhibitors are also substrates of P-gp and capable of _______ inhibiting P-gp function
competitively
true or false: inhibition of P-gp in brain is expected to increase the penetration of P-gp substrates into brain
true
(inc. conc of P-gp substrate into brain)
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?
more
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
true
P-gp in the liver is expressed where?
at bile canaliculus
(bile canalicular membrane of the liver)
true or false: combining paclitaxel with a P-gp inhibitor will likely decrease biliary excretion of paclitaxel
true
(drug is biliary excreted)
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
true
(leads to accumulation)
true or false: there is no P-gp in the placenta
false
(P-gp is part of fetal protection system)
true or false: P-gp inhibitors will likely increase the passage of P-gp substrates across placenta, leading to increased fetal drug levels
true
two xenobiotic substrates to know for OATP superfamily
-fexofenadine
-statins
endogenous compounds for OATP superfamily (3)
bilirubin
bile salts
steroid hormone metabolites (e.g. estradiol glucuronide)
true or false: OATP1B1 in liver pumps drug out of the hepatocyte
false
(pumps drug into hepatocyte)
true or false: OATP1B1 inhibition will likely decrease the intrahepatic concentration of OATP1B1 substrates
true
life threatening side effect of statins
rhabdomyolysis
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
b. gemfibrozil
(it is a OATP1B1 inhibitor)
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
b. gemfibrozil
(this lowers cholesterol and is a OATP1B1 inhibitor)
what is the significance of OATP1B1 CC genotype vs the TC or TT genotype?
CC genotype is linked with a greater incidence of side effects and myopathy
fexofenadine is a substrate of which OATPs? (2)
OATP1A2 and OATP2B1
true or false: grapefruit juice inhibits OATP
true
PEPT1 (peptide transporter 1) is found in which organ?
small intestine
substrates for PEPT1 (peptide transporter 1) (2)
-dipeptides and tripeptides
-beta-Lactam antibiotics
(peptides and antibiotics)
PEPT1 can be used to improve ____ absorption of drugs
oral
PEPT1 example from class
valacyclovir; it is a prodrug and has higher oral absorption. When administered at the same dose, valacyclovir leads to higher systemic exposure to 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?
a. inc brain distribution
b. inc biliary excretion
c. inc intestinal absorption
d. inc drug transfer to fetus
b. inc biliary excretion
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
c. PEPT1
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
b. decreased efficacy of statins
