Drug Transport Flashcards
What types of cells are barriers to the different parts of ADME?
absorption: epithelial (intestine lining)
distribution: endothelial (inside blood cells)
metabolism: hepatocytes (epithelial)
elimination: renal tubules/biliary (epithelial)
What are the two types of membranes and what are they facing?
apical: lumen
basolateral: interstitum
What is paracellular transport?
through intracellular space
What are the types of endothelial cells?
non-sinusoidal fenestrated or sinusoidal fenestrated, non-sinusoidal non-fenestrated (continuous) and sinusoidal non-fenestrated (sinusoidal)
What is the difference between non-sinusoidal and sinusoidal capillaries?
non-sinusoidal capillaries have a continuous basement membrane
What is the difference between fenestrated and non-fenestrated membranes?
pathway for transcellular diffusion or aqueous diffusion
What channels are involved in aqueous diffusion?
mediated by aquaporins or aquaglycoproteins
What are the two types of active transport channels?
ABCs (ATP-binding cassettes) and SLCs (solute carrier transporters)
What is the function of MDR1 or p-glycoprotein?
pumps drugs out of GI lumen, pumps drugs into kidney lumen, pumps drugs from brain to blood
What do SLCs mediate?
cotransport/facilitated diffusion
What receptors help with uptake of neurotransmitters?
SLC6A
At a low pH, what drugs are neutral?
weak acids (protonated) not weak bases (they're protonated but positively charged)
What is the Henderson-Hasselbach equation?
pKa - pH = log(unprotonated/protonated)
What is the ion trapping effect?
pH across membrane determines distribution of drug, because only neutral form can diffuse across membrane
How does ibuprofen display the ion trapping effect?
has pKa of 4.4, due to acidic contents of stomach, it diffuses into the stomach
