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Flashcards in Drug Transporters Deck (18):
1

What are the 4 most important solute carrier superfamily sub-families? What do they do?

1. OAT influx non ATP
2. OATP''
3. OCT''
4. MATE -efflux non ATP

2

What are the 3 most important ATP binding Cassette superfamily sub-families?

1. P-gp/MDR1
2. BCRP
3. MRPs

3

How does the OAT transport organic anions against a negative membrane potential?

1. link facilitated efflux of the counterion: Alpha-ketoglutarate

2. Concentration is maintained by Na/deoxy carboxylate co-transporter

3. Na/K+ ATPase

*tertiary active transporter

4

How do Methotrexate and NSAIDs interact?

NSAIDS are inhibitors of OAT1 trnasport activity
-->Methotraxate cant be taken up into the kidney and stays in the blood and leads to toxicity

5

How does Probenecid prevent Cidefovir induced nephroxicity?

Probenecid prevents neurotoxicity by blocking OAT-1 dependent cidefovir uptake into the proximal tubules

6

What is OATP transport?

electroneutral exchangers
-transports substrates in exchange for HCO3-

7

Where do people have multiple SNP in OATP1B1 what does this influence?

-statin efficacy and systemic exposure

8

What is a potent inhibitor of OATP1B1 and blocks statin uptake?

Cyclosporin

9

What does OCT transport?

influx
-simple passive diffusion of substrates
-(Na+/H+ independent)

10

What does MATE do?

-primarily responsible for secreting OCT-transport substrates

-renal tubular secretions of cationic drugs into the urine
-hepatic elimination of cationic drugs into bile

11

How do SNPs of OCT and MATE affect metformin?

-metformin is very basic anti-diebetic drug that acts in the liver and is elimated unchged by renal tubule

-OCT/MATE SNP--> loss of transporter activity and decreased kidney uptake/excretion --increased systemic drug availability

12

How does cimetidine affect OCT/MATE?

prevents renal elimination of other OCT dependent drugs
-such as procainamide-->increased plasma concentration of procainamide

13

What is cisplatin coadministered with, why?

Cimetidine blocks cisplatin uptake into the kidney and prevents cisplatin induced nephrotoxicity

14

What does Pgp/MDR1 transport?

bulky hydrophobic structures with neutral/positive charge
-specificity overlaps with CYP3A4

-inducers rifampin and st. johns wort--->decreased plasma concentraiton

15

What happens when P-gp inhibitors such as cyclosporin are used with digoxin?

-decreased drug elimination-->toxicity

16

What happens when P-gp inducers such as rifampicin and st johns wort are used with digoxin?

-increased drug efflux
-decreased concentration
-decreased efficacy

17

What happens when loperamide a opioid receptor agonist is used in the treatment of diarrhea? What happens if you give it with cyclosporin?

potent substrate of P-gp therefore does not cross BB

-allows loperamide to cross BBB and enter CNS where it can cause respiratory depression

18

Do cancer cells upregulate or down regulate expression of P-gp?

upregulate--increased efflux of anti-cancer drugs