organic anion and cation transporters:importance in drug metabolism

Question 1

role of organic anion transporters

Answer 1

transport natural substances- butyrate, carnitine, conjugated sex steroids, cyclic nucleotides(vitamins, urate)
transport common drugs- antibiotics, antivirals ,diuretics, nutrients (vitamins, flavnoids)
as they regulate levels key metabolites and signalling molecules they play a role in homeostasis
interorgan and interorganismal communication

Question 2

how does renal organic anion transporter work

Answer 2

sodium pump creates gradient
decarboxylate transporter is the secondary active transport
OAT is tertiary active transport

Question 3

what do OCTs transport

Answer 3

dopamine
serotonin
histamine

Question 4

what are OCT transporters driven bye

Answer 4

negative membrane potential

Question 5

what are multi drug and toxin extrusion proteins (MATE) driven by

Answer 5

pH gradient

Question 6

OCT affect on metformin

Answer 6

metformin is an anti diabetic used to treat type 2 diabetes
it decreases hepatic glucose production
some patients express a polymorphism for OCT1 resulting in OCT1 with reduced activity
hepatic uptake of metformin is reduced, reducing anti-diabetic effects
circulating glucose levels are raised above those expected

Question 7

how can OCT cause toxic drug accumulation (cisplatin)

Answer 7

cisplatin is taken up into cells by OCT2.
sequestering toxic drugs into cancer cells causing cell death.
in kidney OCT2 removes cisplatin from blood to proximal tubule cells.
cisplatin is a poor substrate for MATE proteins so drug is being picked up by proximal tubule cells but not excreted into the urine resulting in nephrotoxicity.
reducing the maximum therapeutic dosage