Drug Disposition: Distribution Flashcards
(1) Name 4 factors that would affect the distribution of a drug.
blood flow
affinity of cells for drug
ability of drug to cross biomembrane
action of liver (enterohepatic cycling)
(2) What is the role of ABC transporters in drug distribution?
ATP-binding cassette transporters (ABC) are transmembrane proteins that can actively extrude a wide variety of endogenous and exogenous compounds (ABC transporters have broad and overlapping substrate specificities)
(2) What is notable about the action of P-glycoprotein throughout its various locations?
P-glycoprotein transporter is always moving substances out of the body- to bile duct, intestinal lumen, kidney tubule and blood to brain
(3) Explain enterohepatic cycling.
bile excreted with conjugated drugs is metabolized by gut bacteria which can cleave off conjugate to reveal parent drug; parent drug can be reabsorbed into portal system (note: decrease in gut flora ie. antibiotic will decrease this process)
(1) Relate drug distribution and the chemical structure of the drug, how are they interrelated?
whether the molecule is lipophillic or aqueous will play a role in the transport across membranes and into tissues
(4) Explain the concept of apparent volume of distribution
if we know the concentration of drug administered and then we can test the concentration in blood after it has circulated we can measure the apparent volume of distribution
(4) Describe the utility knowing/using the apparent volume of distribution.
since the volume of blood in the body is known, the apparent volume of distribution can be compared to estimate the amount of drug that has been absorbed into tissue
(5) Name two drug-binding proteins in plasma. (predominant)
albumin (weak acids) and a1-acid glycoprotein (weak bases)(predominant drug binding sites in plasma)
(5) Where are alternate sites of drug binding within the body besides plasma proteins which render them biologically inactive? (4)
(drugs concentrate conc. in organ due to active uptake)
adipose tissue accumulates lipid-soluble drugs
bone
liver
kidney
(6) Name 4 blood-organ barriers in the body and what they are composed of (what type of junction).
blood-barin (tight junctions between cap. endoth)
blood-thymus (tight junctions protect only cortex)
blood-testis (occluding junctions of Sertoli cells)
blood-ocular (both blood-aqueous and blood-retinal)
(6) Describe how substances enter and exit CSF.
(mostly) only lipophillic compounds cross the BBB freely, xenobiotics can exit the CSF through the venous system
(7) Discuss the movement of drugs across the placenta.
most drugs which cross the placenta do so by simple diffusion, bind of drugs does not impede their passage across the placenta (placenta is not a physical barrier for drugs)
