Placental barrier, distribution

Specific barriers may serve to limit dmg distribution. The placental barrier is of obvious importance to dmg action in the fetus. Dmg transfers across the placenta primarily by Hpid solubiHty. Hence, this barrier is not particularly restrictive. Similarly, the Hpid solubiHty of a dmg is a primary deterrninant in access to the brain and cerebrospinal fluid. Generally, hydrophilic or charged dmgs can also penetrate to these latter areas, but the result is slow and incomplete. The blood brain barrier is composed of cells having tight junctions which are much less permeable to solutes than are the endotheHal cells of other tissues. 

Pentazocine has been successfully used to relieve labour pain [201] and its obstetric use in place of pethidine is favoured by,its apparent inferior ability to pass the placental barrier [206]. A clinical trial of (+)- and (-)-pentazocine adds to the rare number of examples in which optical enantiomorphs have been evaluated [207]. In post-operative patients, response to 60 mg of the dextro isomer was less than that to 5 mg of morphine, while 25—29 mg of (-)-pentazocine was as effective as 10 mg of morphine. Hence most of the activity of the race-mate resides in the laevo isomer, as anticipated from results in animals [208]. Several studies of the distribution, excretion and metabolism of pentazocine have been made. Peak levels of the tritium-labelled drug (and its c/s-3-chloroallyl analogue) were present in the C.N.S. of a cat within 40 minutes of intramuscular administration [209], the comparable figure for morphine being 2 hours [210]. 

Distribution - INH readily diffuses into all body fluids (including cerebrospinal, pleural, and ascitic), tissues, organs, and excreta (saliva, sputum, feces). It also passes through the placental barrier and into breast milk in concentrations comparable to those in plasma. 

Distribution - Tinidazole is distributed into virtually all tissues and body fluids and crosses the blood-brain barrier. The apparent volume of distribution is approximately 50 L. Plasma protein binding of tinidazole is 12%. Tinidazole crosses the placental barrier and is secreted in breast milk. 

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. 

Nicotine is well absorbed from the mucous membranes in the oral cavity, gastrointestinal tract, and respiratory system. If tobacco smoke is held in the mouth for 2 seconds, 66 to 77% of the nicotine in the smoke will be absorbed across the oral mucosa. If tobacco smoke is inhaled, approximately 90 to 98% of the nicotine will be absorbed. Nicotine is distributed throughout the body, readily crossing the blood-brain and placental barriers. The liver, kidney, and lung metabolize approximately 80 to 90% of the alkaloid. The kidney rapidly eliminates nicotine and its metabolites. 

The tetracyclines are distributed throughout body tissues and fluids in concentrations that reflect the lipid solubility of each individual agent. Minocycline and doxycycline are the most lipid soluble, while oxytetracy-chne is the least hpid soluble. The tetracyclines penetrate (but somewhat unpredictably) the uninflamed meninges and cross the placental barrier. Peak serum levels are reached approximately 2 hours after oral administration cerebrospinal fluid (CSF) levels are only one-fourth those of plasma. 

All the belladonna alkaloids are well absorbed from the GIT, from the site of injection and the mucous membrane. They are distributed throughout the body and cross the blood-brain barrier. About 50% of the atropine is metabolized in liver and remaining portion is excreted unchanged in urine. Atropine cross the placental barrier and is secreted in milk and saliva. 

Chloramphenicol is completely absorbed after oral administration, bound to plasma protein (approximately 60%) and widely distributed in body. It crosses the blood-brain and placental barrier and shows its presence in CSF, bile and milk. It is conjugated with glucuronic acid in liver and excreted in urine. Small amount is excreted in urine in unchanged form. 

After oral administration, it is absorbed well and distributed to different body tissues and penetrates meninges, caseous masses and placental barrier. It is metabolized in liver to active deacylated metabolite and induces the microsomal enzymes in liver. It is excreted mainly in bile and urine. 

After oral administration it is well absorbed from gastrointestinal tract and widely distributed throughout body tissues and CSF. It crosses the placental barrier and... 

Tetrahydrocannabinol is metabolized in the liver to form active metabolites which are further metabolized to inactive polar compounds these are excreted in the urine. Some metabolites are excreted into the bile and then recycled via the enterohepatic circulation. Because of their high lipophilicity, most active metabolites are widely distributed in fat deposits and the brain, from which sources they are only slowly eliminated. The half-life of elimination for many of the active metabolites has been calculated to be approximately 30 hours. Accordingly, accumulation occurs with regular, chronic dosing. Traces of the cannabinoids can be detected in the blood and urine of users for many days after the last administration. There is some evidence of metabolic tolerance occurring after chronic use of the drug. THC and related cannabinoids readily penetrate the placental barrier and may possibly detrimentally affect foetal development. 

Spironolactone and canrenone (a major metabolite of the drug) are both more than 90% bound to plasma proteins. Spironolactone or its metabolites may cross the placental barrier, and canrenone is distributed into breast milk [67,78,79]. 

Distribution Sulfa drugs are distributed throughout body water and penetrate well into cerebrospinal fluid, even in the absence of inflammation. They can also pass the placental barrier and into breast milk. Sulfa drugs are bound to serum albumin in the circulation the extent of binding depends on the particular agent. 

Distribution All of the aminoglycosides have similar pharmacokinetic properties. Levels achieved in most tissues are low, and penetration into most body fluids is variable. Concentrations in cerebrospinal fluid are inadequate even when the meninges are inflamed. Except for neomycin, the aminoglycosides may be administered intrathecally. High concentrations accumulate in the renal cortex and in the endolymph and perilymph of the inner ear, which may account for their nephrotoxic and ototoxic potential. All cross the placental barrier and may accumulate in fetal plasma and amniotic fluid. 

The toxicity to the nervous system depends on the delivered dose and exposiue duration. In the case of pregnant women, pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern PAH disposition within the mother and the nervous system of children. Moreover, unique physiological features, such as the presence of a placental barrier and the gradual development of the blood-brain barrier influence PAH disposition and thus modulate developmental neurotoxicity. Because CNS effects are dependent upon windows of susceptibility when the lowest dose and shortest duration of exposure to environmental PAHs will have the greatest negative impact on brain development, a susceptibility exposure paradigm has proven to be the most reliable model in which to study developmental insult. The intent of this chapter was to review... 

Lithium is readily absorbed when administered orally and is widely distributed in the body, mainly intra-cellularly. It is carried into the red blood cells by the sodium transport carrier and enters the central nervous system. Lithium can penetrate the placental barrier. It is excreted in the urine - excretion depends on sodium and water balance and the glomerular filtration rate. 

Lead is one of the systemic poisons, in that once absorbed into the circulation, it is distributed throughout the body where it causes serious health effects. Manifested effects of Pb poisoning include nausea, anorexia, and severe abdominal cramps, weight loss, anemia, renal tubular dysfunction, muscle aches, and joint pains. Lead can pass the placental barrier and may reach the fetus, resulting in miscarriages, abortions, and stillbirths. 

Metallic Mercury. The lipophilic nature of metallic mercury results in its distribution throughout the body. Metallic mercury in solution in the body is highly lipophilic, thereby allowing it to cross blood-brain and placental barriers with ease (Clarkson 1989). Mercury distributes to all tissues and reaches peak levels within 24 hours, except in the brain where peak levels are achieved within 2-3 days (Hursh et al. 1976). The longest retention of mercury after inhalation of mercury vapor occurs in the brain (Takahata et al. 1970). Japanese workers who died 10 years after their last exposure to metallic mercury vapors still had high residual levels of mercury in their brains (Takahata et al. 1970). Autopsies of 3 dentists revealed 0.945-2.110 mg Hg/kg in the renal cortex, compared to 0.021-0.810 mg Hg/kg for unexposed controls (Nylander et al. 1989). 

Metallic and Inorganic Mercury. Data on the distribution of ingested elemental mercury were not located, and data on the ingestion of inorganic mercury are limited. The metallic mercury that is absorbed from an oral exposure is expected to resemble many aspects of the distribution of mercuric salts because metallic mercury is oxidized to mercuric ion in biological fluids, and the resulting distribution reflects that of the mercuric ion. Unlike elemental mercury, however, the amount of divalent mercury that crosses the blood-brain and placental barriers is much lower because of its lower lipid solubility (Clarkson 1989). 

The distribution of mercury in humans and animals appears to be similar. The lipophilic nature of metallic mercury results in its distribution throughout the body in humans (Takahata et al. 1970) and in animals (Berlin and Johansson 1964 Berlin et al. 1966). Distribution of inorganic mercury compounds resembles that of metallic mercury however, human distribution is preferentially to the kidneys, liver, and intestines. Also, levels in the brain are substantially lower, as these compounds have a lower lipophilicity. Distribution of organic mercury compounds is also similar to that of metallic mercury. The ability of methylmercuric compounds to cross the blood-brain and placental barriers enables ready... 

Ethanol is entirely miscible in water and reasonably soluble in lipid. The amphiphilic nature of this small, weakly polar molecule allows it to incorporate readily into the structure of water while at the same time partitioning into hydrophobic environments such as the lipid bilayer. At the concentrations needed to produce a cognitive effect, ethanol will distribute fairly evenly throughout the aqueous and hydrophobic regions of the body, easily crossing the gut, blood-brain and placental barriers. 

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