Exam 2 drug transporters Flashcards
List the components of the blood-brain barrier.
a. 2 barriers system
b. 1st: physical barrier
- Composed Vascular endothelial cell, Astrocytes & Podocytes
- Held together by tight junctions
c. 2nd: is a Protein barrier
Transport & tight junction proteins
Things that can cross BBB
Small lipophilic molecules, ethanol, nicotine, glucose, amino acids, nucleotides
Analyze the anatomic differences between drug transporters in different organs and their overall effects. (Liver, kidneys, GI tract, CSF, placenta)
- Liver: Most transporters are pointed towards liver
- Kidney: Majority transporter movement is into tubule
- GI Tract: Most common transporter is ABCG2
- CSF: Very few transporters. Intrathecal best way to get drugs in
- Placenta: Keep things out of fetal circulation
ABCB1 transporter
- Which drugs?
- Found where?
- Critical in what?
- Broadest specificity
- Pump out antidepressants, cancer drugs, opioids
- Found in GI, kidneys, testes & BBB
- Critical in maintenance of BBB
b. ABCC transporter
- Largest class
- Mainly work with anti-neoplastics efflux
ABCG2 transporter
- BRCA, antineoplastics, toxins, folate
Which drug transporters do not require ATP
- Non-ABC efflux
- SLC-21
Define the role of drug efflux transporters.
- Pump the drug out of the cell into blood stream(Cell survival mechanism)
- Broad specificity
- Most are ATP-binding cassette (ABC) transporters
- Most efflux transporters are B, C, & G
Which transporter effluxes cholesterol?
ABCA1
Which parameters (4) effect passive diffusion?
Molecular weight
pKa
Lipid solubility
Plasma protein binding
Why is there a greater density of tight junctions in the BBB?
Due to stimulus from pericytes & astrocytes.
