Электронная библиотека технического вуза
After absorption, drugs enter the blood, then different organs and tissues. The majority of drugs are distributed unevenly, and only a small number of drugs distributes rather evenly (for example, some general anesthetics). Biologic barriers, that are encountered during drug distribution in the body, substantially influence the distribution: capillary wall, cell (plasma) membranes, blood-brain and placental barriers.
Most of the drugs go through the capillary wall easily, since it is a porous membrane (human pores average 2 nm in diameter). The exception is plasma proteins and their drug complexes. Hydrophilic (water-soluble) compounds pass through capillary wall intercellular clefts and enter interstitial space. There is barely any diffusion through the protein-phospholipid cellular membranes (they can get inside the cells only with transport systems' involvement). Lipophilic compounds penetrate well through capillary endothelium and cell membranes (Fig. II.5).
Fig. II.5. Factors influencing drug distribution.
The passage of a lot of drugs through the blood-brain barrier1 is hindered. This is due to the characteristics of cerebral capillaries' structure (Fig. II.6). First of all, unlike the endothelium of periferal capillaries, their endothelium does not have intercellular clefts through which substances can penetrate well. In cerebral capillaries pinocytosis is actually absent. Glial elements (astroglia) line the external surface of the endothelium and, clearly, play the role of an additional lipid membrane. Polar compounds penetrate through the blood-brain barrier poorly. Lipophilic molecules easily pass through to the cerebral tissues. In general, drugs pass through the blood-brain barrier by means of diffusion, and some compounds - due to active transport. In certain small areas of the brain (epiphysis, neurohypophysis, medulla oblongata, and so on) there is almost no blood-brain barrier. It also has to be taken into account, that in some pathologic conditions (for example, in meningitis) the blood-brain barrier permeability is increased.
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