Ch7 DRUG DISTRIBUTION Flashcards
distribution
the moment of a drug from its site of administration to its site of action
carrier protein
if a drug is bound to a carrier protein, it is not active in any way, and the drug will have its effect only in the unbound form. A drug bound to a carrier protein is similarly unavailable for drug metabolism.
Albumin
the most important of the carriers; many drugs, particularly those that are acidic, bind to this protein. The binding sites on albumin are finite, so drugs and natural compounds compete with each other for binding. Serious interactions can happen when two drugs or molecules that compete for the same site are given simultaneously or when the concentration of one suddenly increases
Sinusoidal capillaries
The most permeable type of capillaries allow the movement of large
amounts of high-molecular-weight material because of very large intercellular clefts and a discontinuous basement membrane.
Sinusoidal capillaries are necessary in the liver because the liver makes albumin and other large proteins and is only able to bring them into the circulation via sinusoids. The spleen removes damaged red blood cells, this too requires extremely permeable capillaries.
fenestrated capillaries
The fenestrations may have across them a thin membrane that acts as a moderate barrier to solutes, or the fenestrations may be pores. Fenestrated capillaries are abundant in areas where large amounts of material must move quickly across the capillary wall, such as the small intestine and the glomerular
capillaries of the kidney.
Continuous capillaries with large pores/intracellular clefts
are found in nervous tissue, skin, placenta and muscle, and they have a variable permeability to solutes
Continuous capillaries without intracellular clefts
found in the blood-brain barrier in the central nervous system
BBB in a fetus
most researchers assume that the tight junctions would not yet have completely formed (so intercellular clefts would still be present in the endothelium of the capillaries) and that the basement membrane and astrocyte foot processes also would not be completely developed - as developed as an adults by 4months
fetus as a compartment for drugs
When the drug concentration in the parent rises, there normally will be a
slight delay, and then the fetus’s drug concentration will mirror parental
levels. The drug is cleared out of the parent fairly quickly, and the fetus is
left with relatively high concentrations.
For example, during prophylaxis for group B streptococci, the parent receives antibiotics intravenously. antibiotic concentrations increase rapidly, and the antibiotics enter fetal blood soon afterward and increase to parental levels. The drug is cleared mainly by the parental kidneys, so the fetus acts like another
nonmetabolizing compartment of the mother.
When do drugs pass most easily into breast milk?
In the first two weeks of breastfeeding, large gaps exist between alveolar cells. These gaps allow immunoglobulins (particularly IgA), maternal white blood cells, and large maternal proteins to pass into the milk easily. These gaps close as the alveolar cells swell, so it is generally assumed that drugs pass into milk much more easily in the immediate postpartum period than at any other time.
important determinants for how much drug will transfer into milk?
a drug’s concentration in human milk is the mother’s plasma level. As the level of the medication in the parent’s plasma begins its rise, the concentration in milk increases as well
Most drugs circulate in the maternal plasma bound to a large molecular- weight protein called albumin, but it is the “free” component that gets transferred into milk.
Almost without exception, extremely lipid-soluble drugs penetrate milk in higher concentrations
Oral Bioavailability
Once a drug has entered the parent’s milk and has been ingested by the infant, it must travel through the infant’s GI tract and be absorbed. The amount of a drug that actually reaches the circulation is called its oral bioavailability
