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which are expressed in apical membrane?
a)SLC 6A4
b)SLC 19A1
c)ABC C2
d)ABC B1
whichever one you pick, what is the name of the transporter that it encodes? |
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Definition
ABC B1
aka MDR1 or P-gp
it is expressed in apical membrane of: GIT, liver, kidneys, brain. With the purpose of moving the drug out for excretion! |
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| For ABC B1 (MDR1, P-gp): Which can lead to increased multi drug resistance? increased efflux/decreased efflux |
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| For ABC B1 (MDR1 or P-gp), which can lead to higher drug levels? increased efflux/decreased efflux |
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| decreased efflux, leads to toxicity. |
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Which of the following has 2x lower expression (lower hepatic levels) in women?
a)SLC 6A4
b)ABC C2
c)ABC B1
d)SLC 19A1 |
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Definition
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| True or False: ABC B1's SNP 3435C>T is a synonymous SNP, therefore it doesnt matter. |
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Definition
| False, although it is synonymous and leads to the same AA, it still has an effect on the mRNA (making it unstable) so that P-gp expression is decreased. |
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| True or False: With the ABC B1 gene, there is a strong LD between 2577G>T and 3435C>T. |
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Definition
| False, it should be 2677G>T |
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| which of the following cods for serotonin transporter? Is it SLC22A1, SLCO1B1, SLC6A4, or ABCC2? |
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| Where are polymorphisms found on the SLC6A4? In the ________ region. Also, Which (LL or SS) is associated with better response to therapy? |
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| Promoter region. Long repeats (LL) means there is greater expression of the serotonin reuptake transporters, so more targets for the drug that wish to inhibit them. |
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| What drug transporter is responsible for moving statins into the hepatocytes? |
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| What drug transporter gene and polymorphism (SNP) is associated with decreased response to statins in Japanese people? |
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| SLC O1B1 (OATP1B1) and its polymorphism SNP521T>C with CC genotype. Less transporting activity, so drug not moved from circulation to hepatocytes, so increase plasma conc but low conc in liver where it needs to be :( Simvastatin, Atorvastatin, and Pravastatin. |
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| What three drugs are mentioned to be affected by polymorphism SNP521 CC genotype? |
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Definition
| statins, prandin (repaglinide), and allegra (fexofenadine). Will cause increased plasma level for all three drugs. Statins will not be able to go to liver and are ineffective. Prandin will have increased risk for hypoglycemia. And allegra will not be affected much because has large therapeutic range! |
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| where are transporters of the gene SLC 22A1 located? What is the name of the transporter? What drug does it affect? |
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Definition
| OCT1 is located on the basolateral membrand of hepatocytes. Has a role in liver metabolism. Affects metformin! There is a variant (with 3 SNPs and 1 deletion) found in certain ethnic groups. It causes decreased efficacy and higher metformin serum levels.. |
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| what drug transporter gene and protein is responsible for Dubin Johnson Syndrome if it is mutated? |
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Definition
| ABC C2 aka MRP2. Causes mild jaundice because nonconjugated bilirubin gets backed up, since MRP2 is not working when it is mutated. MRP2 normally is expressed in hepatocytes and pumps drugs from liver into bile (also from renal tubules to lumen). It favors Phase 2 metabolites, unmetabolized drugs, bilirubin, and some Phase 1 metabolites. |
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| People with Dubin-Johnson syndrome (mild jaundice) have a damaged liver. T/F? |
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Definition
| False. They have mutated ACBC2/MRP2 transporter proteins. |
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| We learned that Methotrexate is involved with which of the following? ABCB1, ABCC2, SLC O1B1, or SLC19A1. |
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Definition
| Two actually. SLC19A1 (RFC-1), and ABCC2 (MRP2). With SLC19A1, there is SNP80A>G and people with GG genotype have less response to methotrexate in RA patients. AA people have a good methotrexate response. In ABCC2, methotrexate is transported into renal tubular cells and not pumped out to the lumen to be excreted :( So accumulates and causes nephrotoxicity. |
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| which of the following is involved with increased CYP3A4 expression? SLCO1B1, SLC19A1, SLC22A1, ABCB1, or ABCC2? |
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| ABCB1, aka MDR1. Low expression of MDR1 can make 3A4 levels increase because trying to compensate. But depends on other drugs, transportes, etc... |
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| ABCB1. the SNP3435 TT haplotype affects digoxin, cyclosporin, chemotherapy, BBB (Parkinsons and epilepsy). |
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| what are the two locations of MRP2? |
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Definition
| aka ABCC2. They are in the hepatocytes (move drugs from liver to bile for excretion) and also in the proximal renal tubular endothelial cells (to move drugs from renal tubules to lumen for excretion) |
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| what are the two drug transporters we learned that move drugs from circulation to hepatocytes? |
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Definition
| OATP1B1 and OCT1. Deficiency or low expression of these could mean less hepatic metabolism (ie less effectiveness) and more drug in the plasma (and more toxicity) |
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