Zusammenfassung
Für den mit dem Problem der Arzneitherapie während der Schwangerschaft konfrontierten Arzt ergibt sich ein Bild, das noch erhebliche Erkenntnislücken aufweist. Man muß davon ausgehen, daß jedes an die Mutter verabreichte Pharmakon und seine Metaboliten auch den Fetus erreichen, wenn auch in Konzentrationen, die häufig geringer sind als diejenigen im mütterlichen Blut. Da aber Stärke und Art der Wirkung auf den Feten weitgehend unbekannt sind, muß man mit unvorhersehbaren Effekten auf den Feten rechnen. Der „Schutz“ durch die Stoffwechselleistung der vorgeschalteten Placenta ist nach den bisher vorliegenden Kenntnissen gering zu veranschlagen, zumal da der Fetus selber Pharmaka nicht inaktivieren kann. Daher kann hier nur auf die Situation hingewiesen werden, ohne daß bestimmte Empfehlungen hinsichtlich der Sicherheit der Pharmaka für Mutter und Fetus gegeben werden können (vgl. Laurence u. Swyer, 1963). Beispiele für die mögliche Gefährdung Neugeborener gibt Kaufmann bereits 1960. Andererseits sollte die Situation zu verstärkter klinischer Aufmerksamkeit anregen, z.B. im Hinblick auf die Entwicklung der Arzneimittelhydroxylasen in Abhängigkeit von Muttermilchernährung oder STH-Bildung. Daß Erkenntnisse aus Tierversuchen z.B. über die Beeinflussung des Arzneimittelstoffwechsels zu therapeutischen Konsequenzen führen können, beweist der Effekt der Glucuronyltransferasestimulierung auf die Hyperbilirubinämie Neugeborener (vgl. Yaffe et al., 1966).
Summary
In the context of pharmacotherapy during pregnancy three aspects have been reviewed: penetration of drugs through the placenta, oxidative metabolism of drugs and other foreign compounds in the feto-placental unit, and the delayed development of the hepatic hydroxylase system in the newly born. Unless proven otherwise for the individual drug in question one must assume that every drug administered to the mother reaches the fetus and exerts its effects there, which unfortunately are not well known regarding their quality as well as their quantity. Although the placenta is a metabolically very active organ and can hydroxylate steroid hormone precursors, its drug metabolizing ability seems to be limited. The fetal hepatic microsomes contain no activity at all. In the newborn drug metabolizing capacities appear only gradually during the first weeks of life, thus partly explaining the greater sensitivity of immature animals towards drugs. The possible mechanisms of the gradual appearance of the respective enzyme systems have been discussed. They are derepression of protein synthesis, inhibition by a fetal inhibitor, or depressing effects of gonadal hormones.
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Netter, K.J. Arzneimittelaufnahme und -abbau während der Fetalperiode. Arch. Gynak. 211, 112–133 (1971). https://doi.org/10.1007/BF00682858
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DOI: https://doi.org/10.1007/BF00682858