Maternal-placental barrier

Placental Barrier The placental barrier consists of several layers of cells between the maternal and fetal circulatory systems. Diffusion of polar drugs is limited. However, lipid-soluble drugs can pass through the barrier. Fetuses are rich in lipids and may form a reservoir for sequestering lipid-soluble drugs. 

Neonatal Cocaine freely crosses the placental barrier, and prenatal exposure to cocaine alters neurobehavioral development in rat pups (Sobrian et al. 1990). The effects on humans exposed prenatally to cocaine is a complicated matter, because so many other concurrent factors contribute to development. Common confounds are prenatal care and maternal polydrug use. Prenatal cocaine use is associated with reduced gestational age, birth weight, body length, and head circumference (Richardson et al. 1999). In children exposed prenatally to cocaine, some studies have shown behavioral differences evident at 1 to 3 years of age (Richardson et al. 1993 Richardson 1998). Associations are also made with impulsivity and attention deficits at age 6 (Leech et al. 1999). 

Heparin is highly bound to plasma proteins and has a short elimination half-life of 1-5 hours depending on the dose. It is distributed to the reticuloendothelial system and metabolized in the liver to inactive metabolites. It does not cross the placental barrier, however there is a risk of heparin-induced maternal osteopenia if it is used throughout pregnancy. 

Acute placental transfer of [ HjSNA was Btudied in pregnant rabbits and mice the chemical readily crossed the placental barrier. In mice, peak concentrations were found 2 h after administration, and fetal concentration was 10 times sb high as that in maternal tissue, n lactating mice, the chemical was found in breast milk at a concentration 10 times that found in plasma.50... 

The placental membranes are also lipoidal in nature and lipophilic drugs (also nonlipid soluble drugs to some extent) can easily cross the placental barrier. It is a contact between the foetal blood and the maternal blood. Drugs are transferred through this barrier by simple diffusion method, once across this, drug molecules circulate in the foetal blood before diffusing back. 

The equilibrium concentration of a chemical in the maternal and fetal circulations depends on different factors for the two circulatory systems. At equilibrium, the concentration of free diffusible chemical is the same on both sides of the placental barrier. If the chemical is bound by plasma protein and the concentration of that protein is lower in the fetus than in the mother, the concentration of the chemical will... 

Chemicals that cross the placental barrier can act directly on the embryo/fetus, and it is likely that the majority of chemicals that cause developmental toxicity act in this way. Teratogenic chemicals are most likely to act directly on the fetus. Some chemicals cause maternal toxicity at high doses but interfere with embryonic or fetal development at lower doses, and these chemicals are of concern in reproductive toxicology. Many of the most widely recognized embiyotoxic or teratogenic chemicals are selectively active in this manner, and the dose that causes developmental toxicity can be much lower than the dose that is toxic to the mother (Khera, 1984). 

The membrane separating fetal blood from maternal blood in the intervillous space, the placental barrier, resembles other membranes, in that lipid-soluble substances diffuse readily but water-... 

Since TCE readily crosses the placental barrier, it may be responsible for respiratory problems encountered in newborn infants. When used as an anesthetic, TCE reduced uterine motility. Increased maternal and fetal mortality were associated with its use as an analgesic (ref. 35. P. 299)-... 

An active transport mechanism has long been suspected to account for the placental barrier that causes maternal and fetal concentrations for many drugs to differ (96 97). Studies of maternal-fetal transport of medications used during pregnancy in HIV-positive women have shown variable penetration into the fetus (98 99). Whereas the maternal-fetal drug ratios for zidovudine lamivudine/ and nevirapine (approximately 0.85 1.0/ and 0.9/ respectively) demonstrate good fetal penetration/ most protease inhibitors/ nelhnavir/ ritonavh/ saquinivir/ and lopinavir/ are known P-gp substrates and do not cross the placenta in detectable levels (98). 

In newborn infants, the blood-brain barrier is not fully developed certain chemicals, like lead, and some endogenous substances, like bilirubin, may therefore enter the brain more easily. Like the brain, but for different reasons, the embryo is also very sensitive to exogenous chemicals circulating in the maternal blood. The placenta is the route by which the developing embryo and fetus exchanges with maternal blood. Its main physiological function is to provide nutrients to the fetus and remove its waste products. In humans, only three layers of cells separate maternal and fetal blood and form what has been termed the placental barrier. 

The compartments and barriers to methylmercury transport in the tissue compartments and placenta are shown in Figure 2-6. The cell membrane is assumed to be the barrier for methylmercury transport for all tissues except the brain and placenta. The barrier to methylmercury transport to the brain is the endothelial cell wall of the cerebral vascular system (the blood-brain barrier). The placenta is modeled as four compartments, with separate transfer constants for placental barrier and placental tissue transport. There is a tissue compartment for both the maternal and fetal sides of the placenta. 

Placental most small molecular weight drugs cross the placental barrier, although fetal blood levels are usually lower than maternal... 

Work mentioned in Section 4.2.3. has indicated that corticotropin is involved in cortisol production in the fetus, but three reasons are there given why the control of production may be complex. At birth two of the three conditions mentioned suffer dramatic change i.e., cortisol can no longer be obtained across the placental barrier from the maternal circulation, and the abundant supply of progesterone from which cortisol might be synthesized is cut off. To maintain control in the face of changes such as these, the mechanism must surely be robust. 

The membrane separating fetal blood from maternal blood in the intervillous space, the placental barrier, resembles other membranes, in that hpid-soluble substances diffuse readily but water-soluble substances either do not or diffuse poorly. Thus, for instance, morphine-induced respiratory depression and miosis may occur in both the mother and her newborn infant. The children of narcotic-addicted mothers will be bom with an addiction to narcotics. 

Meperidine crosses the placental barrier and, even in reasonable analgesic doses, causes a significant increase in the percentage of babies who show delayed respiration, decreased respiratory minute volume, or decreased oxygen saturation, or who require resuscitation. Fetal and maternal respiratory depression induced by meperidine can be treated with naloxone. The fraction of drug that is bound to protein is lower in the fetus concentrations of free drug thus may be considerably higher than in the mother. Nevertheless,... 

Erythromycin diffuses readily into most tissues except the brain and cerebrospinal fluid. Erythromycin crosses the placental barrier and is present in maternal milk [18]. In many animal species and humans, erythromycin is metabolized by the hepatic microsomal cytochrome P-450 mixed function oxidase system. More specifically erythromycin appears to act as a substrate for the cytochrome P-450 3A4 (CYP 3A4) isoform [13]. Erythromycin is excreted primarily in the bile only 2-5% is excreted in the urine. Concentrations in the bile may exceed 10 times those in plasma [19]. 

Unsteady-State Analysis Including Axial Dispersion. As in the previous unsteady-state analysis, the effects of placental barrier tissue oxygen consumption are neglected in this study. For the unsteady-state analysis of the model in which axial dispersion was included, one study was conducted. This study involved placing a step change on the maternal blood velocity to a new maternal blood velocity of 0.125 times the normal in an attempt to determine the effects of axial dispersion on the system at low maternal blood velocities. The discussion of this study is divided into the following two parts first, the effect of axial dispersion on the response of the fetal blood end capillary oxygen concentration, and second, the effect on the transient axial profiles. 

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