Drug Transport

Question 1

Are SLC’s associated with influx or efflux (note exception)?

Answer 1

Influx - Organic Anion Transporters, Organic Anion Transporting Polypeptides, Organic Cation Transporters

Effllux - Multidrug and Toxin Extrusion Transporters (MATE)

Question 2

How do OAT’s work without ATP?

Answer 2

Linked to an a-ketoglutarate antiport

Specifically:

• OA in, aKG out
• aKG in, Na in
• K in, Na out (pumpKin!)

Question 3

OAT drugs

Answer 3

Methotrexate
NSAIDs
Cidefovir

Question 4

What inhibits OATs?

Answer 4

Probenecid

Question 5

OAT drug interactions:

NSAIDS v. Methotrexate

Answer 5

They both use the same receptor.

NSAIDs can block methotrexate clearance uptake into kidney tubules–> toxicity

Relevant for cancer and rheumatoid arthritis

Question 6

OAT drug interactions:

NSAIDS v. Cidefovir

Answer 6

They both use the same receptor.

NSAIDs can block cidefovir clearance –> nephrtoxicity

Question 7

How do OATP’s work without ATP?

Answer 7

Linked to an a-ketoglutarate antiport

Specifically:
- OA in, bicarbonate out

Question 8

Where are most OATs located?

Answer 8

Liver and kidney

Question 9

OAT drug interactions:

Probenecid v. Cidefovir

Answer 9

Probenecid inhibits OAT1

Cidefovir shows severe renal toxicity

Probenecid keeps cidefovir from secretion into the proximal convoluted tubule. It is then eliminated via the glomerulus

Cidefovir is always co-administered with probenecid

Question 10

Where are most OATP’s located?

Answer 10

liver + kidney (reabsorption), intestine (absorption)

Question 11

What types of molecules do OATPs act on?

Answer 11

Amphipathic anions

Question 12

OATP drug

Answer 12

Statins

Question 13

OATP Inhibitors

Answer 13

Cyclosporin

Macrolides

Question 14

OATP Interactions:

Cyclosporin v. statins

Answer 14

Cyclosporin inhibits OATPs, and statins are OATP substrates.

Result: Statins can’t enter the liver and be metabolized –> toxicity

Question 15

OATP 1B1 v. OATP 1B115 polymorphism

Answer 15

Statin stays in blood –> toxicity

Question 16

OCT/MATE drugs

Answer 16

Metformin
Cisplatin
Cimetidine
Procainamide

Question 17

Main role of OCT (influx) /MATE (efflux transporter)

Answer 17

Renal tubular secretion of substrates

Question 18

Effect of cimetidine on OCT/MATE drugs and what this means for cisplatin extretion

Answer 18

Cimetidine blocks OCT-mediated
renal uptake of many drugs thereby
blocking their elimination plasma concentration

In the case of cisplatin, this stops cisplatin from being taken up into the kidney, preventing nephrotoxicity

Question 19

P-gp drugs

Answer 19

Digoxin
Loperamide
Etoposide

Question 20

P-gp inhibitors

Answer 20

Cyclosporin
Verapamil
(Cimetidine)

Question 21

How are pgp inhibitors used to target the brain?

Answer 21

P-gp inhibitors enhance CNS accessibility

by overcoming BBB

Question 22

How do cancer cells exploit pgp properties

Answer 22

They use pgp/mdr transporters to excrete cancer drugs

Question 23

How do rifampin and SJW affect systemic drug availability (via pgp’s)

Answer 23

Rifampin/St. John’s wort induce P-gp expression, increasing drug efflux and decreasing systemic
availability