Capillary cell membranes

The membrane thickness, h, is a constant at the absorption site but may be altered by disease. Drugs usually diffuse very rapidly into tissues through capillary cell membranes in the vascular compartments. In the brain, the capillaries are densely lined with glial cells creating a thicker lipid barrier (blood-brain barrier) causing a drug to diffuse more slowly into brain. In certain disease states (e.g., meningitis) the cell... 

Polymerization allows deoxygenated hemoglobin to exist as a semisolid gel that protrudes into the cell membrane, distorting RBCs into sickle shapes. Sickle-shaped RBCs increase blood viscosity and encourage sludging in the capillaries and small vessels. Such obstructive events lead to local tissue hypoxia and accentuate the pathologic process. 

Equilibrium dialysis of homogenates of kidneys of rats given mercuric chloride, revealed that over 99% of the mercury was not diffusible [40]. Diffusible compounds of mercury have the opportunity to cross the capillary membrane and enter the tissue spaces however, due to chemical affinities for cellular binding sites and the diffusible complex, and the ability to penetrate the cell membrane, not all diffusible complexes of mercury present in plasma lead to tissue accumulation. 

The work of Young et al. [1] provides a classic example of the role of increased H-bonding potential in preventing access to the CNS (crossing capillary and astrocyte cell membranes Figure 4.2). In this example Alog P provided a measure of H-bonding potential. 

Fig. 4 Elution profiles for (A) propranolol (a), promethazine (b), and chlorprom-azine (c) applied separately on a 5-mm ILC column containing cytoskeleton-depleted red blood cell membrane vesicles entrapped in dextran-grafted agarose gel beads (1.4 /amol phospholipid, 0.5 mL/min) and (B), from left to right, acetylsalicylic acid, salicylic acid, warfarin, and pindolol on a capillary continuous bed containing liposomes immobilized by use of C4 ligands (1.0 /xmol phospholipid, 10 /xl./min). The elution volumes in the absence of lipid are shown (a0, b0, and c0, and the arrow, respectively). (Part A is reprinted with permission, with slight modification, from Ref. 26. Copyright 1999 Elsevier Science. Part B is reprinted with permission from Ref. 23. Copyright 1996 Elsevier Science.)...

The plasma membrane, a phospholipid bilayer in which cholesterol and protein molecules are embedded. The bottom layer, which faces the cytoplasm, has a slightly different phospholipid composition from that of the top layer, which faces the external medium. While phospholipid molecules can readily exchange laterally within their own layer, random exchange across the bilayer is rare. Both globular and helical kinds of protein traverse the bilayer. Cholesterol molecules tend to keep the tails of the phospholipids relatively fixed and orderly in the regions closest to the hydrophilic heads the parts of the tails closer to the core of the membrane move about freely. This model is not believed to apply to blood or lymph capillaries. (Reprinted with permission from Bretscher MS. The molecules of the cell membrane. Sci Am 1985 253 104. Copyright 1985 by Scientific American, Inc. All rights reserved.)... 

Mechanism of Action An electrolyte that is essential for the function and integrity of the nervous, muscular, and skeletal systems. Calcium plays an important role in normal cardiac and renal function, respiration, blood coagulation, and cell membrane and capillary permeability. It helps regulate the release and storage of neurotransmitters and hormones, and it neutralizes or reduces gastric acid (increase pH). Calcium acetate combines with dietary phosphate to form insoluble calcium phosphate. Therapeutic Effect Replaces calcium in deficiency states controls hyperphosphatemia in end-stage renal disease. 

Similarly, drugs injected into the SC or IM space are separated from the blood compartment by the endothelial cells of the capillaries. From the interstitial space, such drug molecules must first diffuse toward and then partition into the endothelial cell membrane. After traversing these cells, the drugs must then partition on the luminal, or blood facing, side of these cells into the blood, which carries them away. By this dilution effect, the blood presents sink conditions, thus maintaining a maximal concentration gradient, dCm/dx, to drive diffusion toward the blood. 

Consequently, bioavailability depends on the route of administration as well as the drug s ability to cross membrane barriers. Once in the systemic circulation, further distribution into peripheral tissues may also be important in allowing the drug to reach the target site. Many drugs must eventually leave the systemic capillaries and enter other cells. Thus, drugs have to move across cell membranes and tissue barriers to get into the body and be distributed within the body. In this section, the ability of these membranes to affect absorption and distribution of drugs is discussed. 

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