Grundsätze der Katecholamintherapie

Zusammenfassung.

Das sympathische Nervensystem kontrolliert zusammen mit dem Parasympathikus alle vegetativ innervierten Strukturen und Organe des Körpers. Noradrenalin, Adrenalin und Dopamin werden als körpereigene Katecholamine im sympathischen Nervensystem gebildet und entfalten ihre spezifischen Wirkungen über Adrenozeptoren, Dopamin zusätzlich über dopaminerge Rezeptoren. Die „klassische” Gruppierung der Adrenozeptoren bestand aus α₁-, α₂-, β₁- und β₂-Subtypen, die in den letzten Jahren durch Gentypisierung weiter differenziert wurden. Adrenozeptoren, in die Zellmembran eingelagerte Proteine, binden auf der Zellaußenseite den Agonisten und setzen auf der Zellinnenseite über eine Interaktion mit G-Proteinen die Erregung in einen intrazellulären Effekt um. Auf Grund seiner hohen Potenz an den kardialen β-Adrenozeptoren führt Adrenalin zu einem ausgeprägten Anstieg der Herzfrequenz und des Herzzeitvolumens und bei einer Dosierung > 0,1 µg/kg·min über die Stimulierung der α-Adrenozeptoren zu einem deutlichen Anstieg des peripheren Widerstandes. Das Wirkprofil von Noradrenalin zeichnet sich durch einen vorherrschenden Effekt auf α-Adrenozeptoren aus, wodurch die Herzfrequenz trotz gleichzeitiger Stimulierung der kardialen β₁-Adrenozeptoren weniger ansteigt als unter Adrenalin. Dopamin hingegen ist an den β- und α-Adrenozeptoren ein niedrig potentes Katecholamin, bewirkt aber durch einen spezifischen Effekt an dopaminergen Rezeptoren zusätzlich eine Vasodilatation in der Niere und im Splanchnikusgebiet. Dobutamin, ein relativ spezifischer Aktivator der β-Adrenozeptoren, führt im Gegensatz zu Dopamin zur Abnahme des pulmonalen Gefäßwiderstandes. Dopexamin wirkt bevorzugt an β₂-Adrenozeptoren und in geringerem Maße an dopaminergen Rezeptoren, woraus insgesamt eine Vasodilatation resultiert. Orciprenalin stimuliert praktisch ausschließlich β-Adrenozeptoren und führt zu einem Anstieg der Herzfrequenz und des Herzzeitvolumens kombiniert mit einem Abfall des systemischen Gefäßwiderstandes. Phosphodiesterase-III-Hemmer erhöhen unabhängig von Adrenozeptoren den intrazellulären cAMP Spiegel durch Blockade der abbauenden Enzyme und wirken positiv inotrop und vasodilatierend.

All involuntary innervated structures of the body are controlled by the sympathetic and parasympathetic nervous system. Adrenaline, noradrenaline and dopamine are endogenous catecholamines binding to adrenergic and dopaminergic receptors, respectively, to mediate their clinical effects. Adrenoceptors are classified as α₁, α₂, β₁ and β₂ subtypes which were even further subcharacterized the recent years. Adrenoceptors are membrane proteins interacting with the agonist and, thus, inducing G-protein mediated intracellular effects. Adrenaline induces an extensive increase of heart rate and stroke volume mediated by β-adrenoceptors and significantly enhances peripheral vascular resistance by α-adrenoceptor stimulation, when administered beyond 0.1  µg/kg·min. In contrast, the clinical effects of noradrenaline are predominantly characterized by α-adrenoceptor stimulation resulting in a less pronounced increase of heart rate. Dopamine, less potent on adrenoceptors, shows additional effects on renal as well as on splanchnic circulation mediated by dopaminergic receptors. Dobutamine, primarily acting on β-adrenoceptors, results in positive inotropic effects without an increase in vascular resistance. Dopexamine, a synthetic catecholamine, induces vasodilation via β₂-adrenoceptor stimulation and potentially increases splanchnic blood flow by additional effects on dopaminergic receptors. Isoproterenol, the classical β-adrenoceptor agonist, mediates positive inotropic effects and causes a major increase in heart rate and a significant decrease of systemic vascular resistance. Independent on adrenoceptors, phosphodiesterase-III-inhibitors exert positiv inotropic and vasodilating activity by an increase in intracellular cAMP concentration induced by inhibition of cAMP hydrolysis.

Schlüsselwörter:

Sympathikus - Katecholamine - & - 945;- und & - 946;-Adrenozeptoren - dopaminerge Rezeptoren

Key words:

Sympathetic nervous system - Catecholamines - Receptors, adrenergic, alpha, beta, dopamine

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