Ontogenese anästhesierelevanter Rezeptoren

Zusammenfassung.

Die Besonderheiten in der medikamentösen Therapie bei Kindern, insbesondere bei Früh-, Neugeborenen und Säuglingen haben ihren Ursprung nicht nur in der durch Organunreife (Leber, Niere etc.) bedingten speziellen Pharmakokinetik, sondern auch in pharmakodynamischen Faktoren, die aus einer noch nicht abgeschlossenen Reifung des Nervensystems resultieren. Auf allen Ebenen der Informationsweiterleitung - vom Nerv mit der elektrischen Übertragung bis zu der Synapse mit der Neurotransmitterübertragung - liegen noch Reifungsdefizite vor, auch wenn die Informationswege und damit ihre Schaltkreise schon prinzipiell angelegt sind. In dem vorliegenden Übersichtsartikel soll schwerpunktmäßig auf die Ontogenese der Rezeptorsysteme eingegangen werden, ein kleinerer Teil des Beitrages widmet sich auch der Frage der Myelinisierung. Die Zahl und Verteilung der Rezeptoren darf bei Früh-, Neugeborenen und Säuglingen jedoch nicht nur auf dem Hintergrund der Funktion im Erwachsenenalter - Informationsweiterleitung und -modifikation - gesehen werden, vielmehr haben die Rezeptoren während des Reifungsprozesses wichtige Funktionen für die Entwicklung der Nervenbahnen, die Ausbildung der Synapsen und die Differenzierung der Nervenzellen selbst. Prinzipiell kann sich die Zahl der Rezeptoren perinatal wie folgt verändern: 1. Kontinuierlicher Anstieg bis zur Reife, 2. Anstieg bis zu einem Maximum während der Entwicklung mit anschließender leichter oder stärkerer Reduktion, 3. Initial hohe Rezeptorzahl mit anschließender deutlicher Reduktion, 4. In etwa gleich bleibende Rezeptorzahl während der gesamten Entwicklung oder 5. nur vorübergehende Expression während der Entwicklung. In dieser Arbeit soll anhand tierexperimenteller und humanpharmakologischer Studien ein Überblick über die Ontogenese der Opioid-, NMDA-, GABA-, Dopamin-, Acetylcholin- und Serotoninrezeptoren gegeben werden. Aus den vorliegenden tierexperimentellen und humanpharmakologischen Daten sollen vorsichtige Schlüsse gezogen werden, wie die Besonderheiten in den Wirkungen der Medikamente bei Kindern (z. B. verstärkte Atemdepression nach Opioidgabe bei Früh- und Neugeborenen, höhere Inzidenz paradoxer Reaktionen auf Benzodiazepine etc.) erklärt werden können.

Ontogenesis of Anesthesia-Relevant Receptors.

The particularities in the medical treatment of children, especially those concerning premature infants, new-borns and babies, do not only stem from the immaturity of the organs (kidneys, liver etc.) but also from pharmacokinetic factors which are result of the immaturity of the brain. There are maturation deficits on all levels of transmission, from the nerve with electric transmission to the synapsis with neurotransmitter propagation, even though the whole system is basically laid out. The presented paper concerns itself mainly with the ontogenesis of the receptor-systems, a small part is dedicated to the question of myelination. Number and distribution of the receptors in premature or new-born infants and babies should not only be viewed in the context of the future function in mature humans (i.e. transmission and modification of information) - the receptors themselves are important factors in the maturing process of neuronal pathways, synapses and the differentiation of the neuronal cells themselves. Basically the number of receptors can change as follows: 1. Continuous increase until maturity, 2. Increase to a maximum during maturation with slight or stronger decrease after, 3. High initial number with following distinct decrease, 4. Even number throughout maturation, 5. Passing expression during maturation. The aim of this paper is to present an overview on the ontogenesis of opioid-, NMDA-, GABA-, dopamine-, acetylcholine- and serotoninreceptors. The data derived from animal and human-pharmacological experiments will be used to carefully conclude how the particularities of drug reactions of children (i.e. increased respiratory depression after opioid application in premature and newborn infants, higher incidence of paradox reactions to benzodiazepines etc.) can be explained.

Schlüsselwörter:

Ontogenese - Opioidrezeptoren - NMDA-Rezeptoren - GABA-Rezeptoren - Dopaminrezeptoren - Acetylcholinrezeptoren - Serotininrezeptoren - 5-NT-Rezeptoren - Frühgeborene - Neugeborene - Myelinisierung

Key words:

Ontogenesis - Opioidreceptors - NMDA-receptors - GABA-receptors - dopaminreceptors - acetylcholinereceptors - serotininreceptors - 5-NT-receptors - premature - new-born infants - myelination

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