Elimination teratogenic effects

The mechanisms that underlie ethanol s teratogenic effects are unknown. Ethanol rapidly crosses the placenta and reaches concentrations in the fetus that are similar to those in maternal blood. The fetal liver has little or no alcohol dehydrogenase activity, so the fetus must rely on maternal and placental enzymes for elimination of alcohol. 

Teratogenicity study in rabbits, dermal application no teratogenic effects at 300mg/kg/day. Ecotoxicity Not easily biodegradable degree of elimination 14% (closed bottle test). 

EHC monographs examine the physical and chemical properties and analytical methods sources of environmental and industrial exposure and environmental transport kinetics and meta-bohsm including absorption, distribution, transformation, and elimination short- and long-term effects on animals, carcinogenicity, mutagenicity, and teratogenicity and finally, an evaluation of risks for human health and the effects on the environment. 

Thalidomide was in 2006 approved by the FDA for the treatment, in combination with dexametha-sone, of newly diagnosed multiple myeloma patients. Thalidomide was sold in the late fifties as an hypnotic, with the infamous epidemic of birth defects as a result. Thalidomide is racemic and the S enantiomer is teratogenic. However the enantiomers interconvert in vivo, so giving only the R enantiomer cannot be a solution. After oral administration peak levels are reached in 2-A hours. It is eliminated mainly by biotransformation with a halfiife of about 6 hours. The most common side effects observed with use of thalidomide in myeloma include drowsiness or fatigue, constipation, dizziness, dry skin or rash, low white blood cell counts, and peripheral neuropathy. 

Lenalidomide, a derivative of thalidomide, was introduced in 2004. Patients with multiple myeloma stage II/III, who have undergone at least one previous treatment can be treated with bortezomib or with lenalidomide in combination with dexamethasone. There is good oral absorptin with peak plasma levels at 0.5-4 hours. Lenalidomide is maily eliminated by the kidneys with a half-life of circa 3-9 hours. Teratogenicity cannot be excluded. Side effects include thrombosis, pulmonary embolus, and hepato-toxicity, as well as bone marrow toxicity resulting in neutropenia and thrombocytopenia. 

The lack of followup data on volunteers prevents certainty in predicting occurence or absence of delayed effects. The compounds are eliminated very rapidly from the body, but they produce a variety of acute effects that are short-lived and reversible, such as gastrointestinal distress after oral administration, pain at an injection site, dizziness, headache, and ocular discomfort. The Committee found no conclusive studies of carcinogenicity, mutagenicity, teratogenicity, or reproductive anomalies associated with the four oximes and therefore did not reach a conclusion in this regard. 

It is highly unlikely that xenon participates in biochemical reactions although it has been shown to have an inhibitory action at NMDA receptors. It has also been reported by Petzelt in 1999 to inhibit Ca2+ regulated transitions in the cell cycle of human endothelial cells. Elimination of xenon is almost entirely through the lungs. Unlike nitrous oxide, xenon does not appear to have any adverse effects on the bone marrow, and there is no evidence of teratogenicity or fetotoxicity. 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25-50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal species studied to date, which is of special concern in view of the drug s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years. 

A 6 month inhalation study was conducted in rats in which the animals were exposed daily to 10 mg m At 3 months, neuromuscular depression, lymphopenia, neutrophilia, and decreased oxygen consumption were observed. In the fifth month, increased organic sulfate elimination, variation in weight, arterial pressure, liver function, and protein metabolism were observed. Liver damage was reported upon histological examination. Studies on the teratogenic, embryotoxic, and cytogenic effects of 2-ME have been inconclusive. 

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