Blood-tissue barrier brain

In some instances, P-gp can significantly affect the profile of drug distribution from systemic circulation into organs and tissues, most notably those that possess a specialized blood-tissue barrier such as the brain. Experiments with mdrla(—/—) mice have shown how P-gp affects the distribution of its substrates into certain tissues (11,12,124,212-219). A few examples are shown below to demonstrate the role played by P-gp in the tissue distribution of drugs. 

Other blood-tissue barriers (e.g., blood-thymus, blood-testis) are less well defined [55,56]. An air-blood barrier also has been described that affects the systemic uptake of aerosolized molecules [57]. Therapeutants that target glycoprotein adhesion molecules on endothelium might surmount the blood-brain or other tissue barriers [58]. 

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Fatty acids are oxidized in several tissues, including liver, muscle, and adipose tissue, by the pathway of P-oxidation. Neither erythrocytes nor brain can use fatty acids, and so continue to rely on glucose during normal periods of fastii. Erythrocytes lack mitochondria, and fatty acids do not cross the blood-hrain barrier efficiently. 

Although the CNS is protected from a number of xeno-biotics by the blood-brain barrier, the barrier is not effective against lipophilic compounds, such as solvents or insecticides (Fig. 7.1). Similarly, the peripheral nervous system is protected by a blood-neural barrier. The barriers are less well developed in the immature nervous system, rendering the fetus and neonate even more susceptible to neurotoxicants. Neural tissue susceptibility is due in large part to its high metabolic rate, high lipid content, and for the CNS, high rate of blood flow. 

Pharmacokinetics (i.e. study of the movements of a medication) antipsychotics and other medications show differences in absorption, distribution, metabolism and excretion as a result of their different chemical structures and pharmaceutical preparations (capsule, tablet, injectable) and in relation to the conditions within the body (see Chapter 5). The transfer of a medication from the blood into the brain tissue across the so-called blood brain barrier, its binding to specific brain structures and thus its actions depend on the physicochemical properties of the molecule. The interplay of these and other factors explains why antipsychotics of different chemical structures are not equally effective milligram for milligram (Table 1.2 column 3) and why they differ with regard to onset and duration of action. 

The entry of toxins into the brain and central nervous system (CNS) is frequently more difficnlt than into other tissues. The function of this blood-brain barrier is related to impaired permeability of the blood capillaries in brain tissne, the necessity for toxins to penetrate glial cells, and the low protein content of the CNS interstitial flnid (Klaassen, 1986). Lipid solnbihty of a toxin is an important factor in the penetration of the blood-brain barrier. 

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