Pharmacology of Drug Transporters

Question 1

Describe how probenecid contributes to interactions with some drugs through transporters

Answer 1

Probenecid is a potent inhibitor of OAT1

Question 2

Describe an example of intentional blockage of transporters by Probenecid

Answer 2

Can be given with cidefovir to treat retinitis; prevents nephrotoxicity normally caused by cidefovir because OAT1 transport can no longer occur in the proximal tubules

Question 3

Describe OATP1B1 as an influencer int he pharmacokinetics of the statin class of drugs.

Answer 3

Responsible for principle effects in the liver (first-pass effect). Multiple SNPs in this transporter influences statin efficacy and systemic exposure. Mutation could reduce statin uptake and lead to toxicity.

Question 4

Describe the mechanism by which cimetidine contributes toward toxicity with drugs transported by the OCT class of drug transporters

Answer 4

Most interactions with OCT/MATE are caused by cimetidine. It is extensively eliminated by the kidney, so it prevents renal elimination of other OCT-dependent drugs and could cause toxicity.

Question 5

How can cimetidine and its interactive effects be used beneficially?

Answer 5

It can be used to block nephrotoxic drug uptake in the kidney and prevent its nephrotoxic effects.

Question 6

Describe the role of the ATP-binding class of transporters in contributing toward the integrity of the blood-brain barrier.

Answer 6

P-gp/MRCP/BCRP ABC family are efflux pumps that form the barrier to a large range of drugs and other compounds by actively transporting these compounds back into the blood and preventing entry into the CNS.

Question 7

What types of molecules are evaded by the ABC transporter system at the BBB?

Answer 7

Small lipophilic molecules (

Question 8

Cyclosporin’s effect on drug transporters

Answer 8

Decrease P-gp/MDR efflux activity, reducing the amount of drug elimination in digoxin and increasing risk of toxicity

Question 9

Describe rifampicin/St. John’s wort’s effects on drug transporters

Answer 9

Increases expression of P-gp and other ABC transporters, increasing drug efflux and decreasing drug efficacy

Question 10

Describe the role of P-gp/MDR1 in determining the responsiveness of tumor cells to chemotherapeutic drugs

Answer 10

Tumor cells often upregulate the expression of P-gp/MDR because it effluxes the anti-cancer drugs more readily and makes them less effective at killing the tumor