Flashcards in Drug Transporters Deck (18):
What are the 4 most important solute carrier superfamily sub-families? What do they do?
1. OAT influx non ATP
4. MATE -efflux non ATP
What are the 3 most important ATP binding Cassette superfamily sub-families?
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
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
How does Probenecid prevent Cidefovir induced nephroxicity?
Probenecid prevents neurotoxicity by blocking OAT-1 dependent cidefovir uptake into the proximal tubules
What is OATP transport?
-transports substrates in exchange for HCO3-
Where do people have multiple SNP in OATP1B1 what does this influence?
-statin efficacy and systemic exposure
What is a potent inhibitor of OATP1B1 and blocks statin uptake?
What does OCT transport?
-simple passive diffusion of substrates
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
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
How does cimetidine affect OCT/MATE?
prevents renal elimination of other OCT dependent drugs
-such as procainamide-->increased plasma concentration of procainamide
What is cisplatin coadministered with, why?
Cimetidine blocks cisplatin uptake into the kidney and prevents cisplatin induced nephrotoxicity
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
What happens when P-gp inhibitors such as cyclosporin are used with digoxin?
-decreased drug elimination-->toxicity
What happens when P-gp inducers such as rifampicin and st johns wort are used with digoxin?
-increased drug efflux
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