Drug Transporters

Question 1

What happens when there is a decrease in the uptake or the efflux of drug in the liver or kidney?

Answer 1

It will lead to increased plasma concentration of the drug which can lead to increased toxicity.

Question 2

What happens where there is an increase in the uptake and a decrease in the efflux in the target organ for the drug?

Answer 2

It will lead to increased concentration of drug in the target organ and increased toxicity.

Question 3

What happens when there is an inhibition of transport of drugs?

Answer 3

The concentration in the blood will be increased which can lead to increased toxicity.

Question 4

How do drug-drug reactions impact transport?

Answer 4

Drug B can block a transporter for Drug A, causing Drug A to build up in the plasma and so the high concentration of Drug A can lead to toxicity and/or decrease the efficacy of the drug as it isn’t reaching the target organ.

Question 5

What are the transporters of the solute carrier superfamily (SLC)?

Answer 5

OAT
OATP
OCT
MATE

Question 6

What are the transporters of the ATP-binding cassette superfamily (ABC)?

Answer 6

P-gp/MDR1
BCRP
MRP

Question 7

OAT

Answer 7

Organic Anion Transporter

Question 8

How does OAT transport?

Answer 8

Uptake

Antiports an organic anion and a-ketoglutarate

Question 9

Where is OAT found?

Answer 9

Liver

PT of kidney

Question 10

What does OAT transport?

Answer 10

Low MW organic anions

Question 11

How does methotrexate and NSAIDs interact with OAT?

Answer 11

NSAIDs block the activity of OAT and methotrexate cannot be taken into the kidney leading to methotrexate toxicity

Question 12

How is probenecid used with cidefovir and OAT?

Answer 12

Probenecid prevents Cidefovir renal uptake which blocks cidefovir-induced nephrotoxicity

Question 13

OATP

Answer 13

Organic Anion Transporter Polypeptides

Question 14

How does OATP transport?

Answer 14

Antiprotons organic anion and HCO3-

Question 15

Where is OATP found?

Answer 15

Gut
Liver
Kidney PT

Question 16

What does OATP transport?

Answer 16

Uptake

Amphipathic anions of MW > 350 Da

Question 17

What are the problems with OATP SNPs and statins?

Answer 17

Some OATP polymorphisms lead to decreased statin transport which reduces their efficacy and increases their toxicity

Question 18

What is the effect of cyclosporin on OATP and statins?

Answer 18

Cyclosporin block OATP, which blocks STATIN uptake and causes STATIN toxicity

Question 19

OCT

Answer 19

Organic Cation Transporter

Question 20

How does OCT transport?

Answer 20

Uptake

Simple facilitated diffusion of organic cations

Question 21

Where is OCT found?

Answer 21

Gut
Liver
Kidney

Question 22

What does OCT transport?

Answer 22

Small cations

Question 23

MATE

Answer 23

Multidrug and Toxin Extrusion Transporter

Question 24

How does MATE transport?

Answer 24

Efflux

Antiports H+ and cationic drugs

Question 25

Where is MATE found?

Answer 25

Liver | Kidney

Question 26

What does MATE transport?

Answer 26

Main role is in secretion of the OCT substrates

Question 27

What can SNPs of OCT/MATE cause?

Answer 27

It can cause the loss of either of these transporter's activities which will lead to increased drug toxicity

Question 28

How does cimetidine affect OCT/MATE and procainamide?

Answer 28

Cimetidine blocks OCT-mediated renal uptake of many drugs like procainaminde which blocks their elimination and increases their plasma concentration

Question 29

How does cimetidine affect OCT/MATE and cisplatin?

Answer 29

Cimetidine blocks OCT uptake of cisplatin and prevents the nephrotoxic effects of cisplatin

Question 30

P-gp/MRD1

Answer 30

P-glycoprotein/Multidrug Resistant Protein 1

Question 31

How does P-gp/MRD1 transport?

Answer 31

Efflux | Active Transport

Question 32

Where is P-gp/MRD1 found?

Answer 32

Intestine Kidney Liver

Question 33

What does P-gp/MRD1 transport?

Answer 33

Bulky hydrophobic neutral or positively charged molecules

Question 34

How does cyclosporin affect P-gp/MRD1 and digoxin?

Answer 34

Cyclosporin inhibits P-gp-mediated elimination of digoxin which increases availability and toxicity as digoxin has a narrow therapeutic range

Question 35

How do rifampicin and St. John's Wort affect P-gp?

Answer 35

Both induce Pg-p and will lead to increased drug efflux, leading to decreased drug efficacy

Question 36

How does cyclosporin affect loperamide and P-gp?

Answer 36

Cyclosporin inhibits P-gp, which will enhance CNS accessibility by overcoming BBB and allow loperamide to pass the BBB and enter the CNS leading to respiratory depression

Question 37

How do tumor cells use P-gp?

Answer 37

Tumor cells up regulate P-gp by up regulating it which allow them to have high efflux of anti-cancer drugs

Question 38

BCRP

Answer 38

Breast Cancer Resistant Protein

Question 39

What is the general function of BCRP?

Answer 39

Concentrates breast milk

Question 40

Where is BCRP found?

Answer 40

Breast Gut Liver BBB

Question 41

What does BCRP transport?

Answer 41

Transports neutral and negatively charged compounds like statins

Question 42

MRP

Answer 42

Multidrug Resistant Protein

Question 43

Where is MRP found?

Answer 43

Many tissues

Question 44

What does MRP transport?

Answer 44

Transports positive amphipathic molecules

Question 45

How is the BBB maintained?

Answer 45

It is maintained via an ABC transporter that actively pumps compounds like drugs out to the blood and keeps them out of the CNS.