INR
-time it takes for blood to clot (prothrombin time) and compares it to a standard or control
bleeding risk
INR>3 signifies _______
clot risk
INR<2 signifies ________
VKORC1
Which gene does Warfarin inhibit?
leads to decrease of VKORC1 transcription factors and less protein
VKORC1 mutation effects?
more sensitive
People with a mutation in the VKORC1 gene are _________ to warfarin
CYP2C9
Warfarin is metabolized by ______
bleeding risk
People with CYP2C9*3/*3 alleles are associated with __________ in regards to Warfarin.
ATP-Binding Cassete
-efflux
-active transporters that are ATP-dependent
-work against the concentration gradient
Solute Carrier transporter
-influx
-family that contains both active and passive transporters that rely on electrical gradient
MDR1, MRP, MXR
What are our major efflux transporters?
OCT, OAT
What are our major influx transporters?
Organic cation transporters (OCT)
-found in kidney and liver tissue, mediate the uptake of organic cations from the blood into the tubules or mediate the uptake of organic cations into the hepatocytes where they are exposed to drug metabolizing enzymes.
Organic anion transporters (OAT)
- found in the intestines, liver, and kidneys
-mediate the uptake of anions (primary focus)
MDR1
-encodes for P-glycoprotein
encodes for P-gp pumps that remove foreign substances out of the cell
What is the primary function of ABCB1?
gene expression (how much protein is made), functionality of P-gp (which substrates will bind)
P-gp function is dependent on 2 factors, what are they?
can't efflux morphine out of neurons and back into bloodstream; too much analgesic effect
What happens to patients who have ABCB1 mutation in regards to morphine?
SLCO1B1
OATP1B1 encodes for what protein?
can't influx statin into their cell; results in high plasma concentrations
What are the implications of someone who has a genetic mutation in OATP1B1?