Lecture 6 - OATs And OCTs (Importance In Drug Metabolism) Flashcards
What does SLC stand for?
Soluble Carrier transport protein
What is SLC22?
Subfamily of SLCs that contain the 2 subfamilies of OATs and OCTs
What does OATs stand for?
Organic Anion Transporters
What does OCTs stand for?
Organic Cation Transporters
Where are OATs usually located?
Localised to epithelial cells where theres a barrier between fluid compartments
What are some examples of where OATs are expressed?
Kidney (between urine and plasma)
Brain (between CSF and plasma)
What is the clinical importance of OATs?
Mediate uptake of antibiotics, antivirals, diuretics and NSAIDs that are organic anions
What type of transport do substrates cross OCTs by?
Facilitated diffusion (use electrochemical gradient)
Where are OCTs found?
MANY TISSUES
What are some important drugs that are affected by OCT activity?
Cisplatin
Metformin
Amiloride
What is the function of Amiloride?
Diuretic treats hypertension
What is the function of Cisplatin?
Chemotherapy for cancers
What is the function of Metformin?
Anti diabetic drug treats type 2 diabetes
Do OATs and OCTs move substances into or out of cells?
INTO (UPTAKE TRANSPORTERS)
If the function of OATs and/or OCTs are affected, what happens to the metabolism of drugs?
Affected
If drugs are cations at physiologically pH, what transporter is important for their uptake?
OCTs
Why is expression of OATs/OCTs very important for drug action?
Certain drugs need them to reach target site
Why are OATs and OCTs important in drug elimination?
They shorten plasma half life of the drug
OATs/OCTs in kidney allow them to be removed
What is the advantage of blocking OATs/OCTs when administering drugs?
Prevent their elimination by the kidney
What is the function of probenecid ?
Blocks the OATs for penicillin helping increase its effectiveness
How do OATs transport OA- from blood to kidney cell?
Na/K+ ATPase establishes Na= gradient
Dicarboxylate transporter tranports DC- (2º active trans) into PCT cell
OATs antiport OA- into PCT and DC- back into blood (3º active trans)
How are OC+ removed from the blood in the kidney by OCTs?
OCT2 Uniporter OC+ into PCT cell
OC+ moves into filtrate via MATE and MATE2-K transporters bringing H+ into PCT
How does metformin help treat Type 2 diabetes?
Reduces production of glucose by the liver
Which transporter is important for metformin transport?
OCT1
How does Cisplatin act as an anti cancer drug?
Enters cells of tumour
Alkalinising agent
Disrupts cells DNA killing cell
What side effects are common with Cisplatin as a chemotherapy agent?
Kidney damage
Hearing loss
Sensory neuropathy
Why does cisplatin have a high toxicity to normal cells killing cells and causing its common side effects?
Cisplpatin = good substrate for OCT 2 (TAKEN INTO CELL WELL)
Poor substrate of MATE1 or MATE2-K (NOT REMOVED WELL)
Accumulates in cell and dies
