Zusammenfassung
Influenza-Epidemien verursachen auch heute noch — trotz breit angelegter Impfkampagnen-jährlich weltweit Zehntausende von Todesfällen, insbesondere in den Risikogruppen der älteren oder immungeschwächten Menschen. Die zur Zeit als zugelassen verfügbaren Arzneimittel zur Prophylaxe bzw. Therapie sind Amantadin oder Rimantadin, bei deren Anwendung aber gravierende Probleme auftreten: keine Wirkung gegen Influenza B, schnelle Resistenzentwicklung und deutliche Nebenwirkungen. Dagegen zeigen gezielt entwickelte, gegen influenza-spezifische Neuraminidasen gerichtete Hemmstoffe wie das nur inhalativ anzuwendende Zanamivir und das auch oral verfügbare GS4071/GS4104 sowohl in vitro als auch in Tiermodellen und in experimentellen Humanstudien eine prophylaktische und therapeutische Wirksamkeit gegen Influenza A und B, gekoppelt mit einer geringen Nebenwirkungsrate. In Zellkulturmodellen sind gegen beide Substanzen resistente Influenza-Stämme aufgetreten, das Ausmaß der Resistenzentwicklung bei klinischer Anwendung der Neuraminidase-Inhibitoren ist aber noch ungeklärt. Der bisher erkennbar größte Nachteil der Neuraminidase-Inhibitoren besteht darin, daß die Therapie wie bei der Anwendung von Amantadin/Rimantadin innerhalb von 30 bis 48 Stunden nach Einsetzen der Symptome beginnen muß, was für den klinischen Alltag eher unrealistisch erscheint. Noch bleibt es gezielt angelegten klinischen Studien vorbehalten zu zeigen, ob Neuraminidase-Hemmstoffe, die bisher überwiegend nach experimentellen Daten beurteilt werden können, tatsächlich imstande sind, in den für die Influenza besonders empfänglichen Risikogruppen die Morbidität, den Krankheitsverlauf und die Mortalität bei prophylaktischer und therapeutischer Anwendung positiv zu beeinflussen.
Summary
Despite wide-spread immunisation programs epidemic influenza continues to cause ten thousands of deaths worldwide, every year, especially in the high risk groups of elderly or immunocompromised persons. At present, amantadine and rimantadine are the only approved agents available for prophylactic and therapeutic use, yet, the deployment of these substances is problematic: neither of the two drugs is effective against influenza B, their use is accompanied by rapid development of viral resistance, and they show many adverse effects. In contrast, zanamivir and GS4071/GS4104 are rationally developed influenza-specific neuraminidase inhibitors, proving prophylactic and therapeutic efficacy against influenza A and B, as well in vitro as in animal models, and in experimental human studies. Zanamivir and GS4071/GS4104 are well tolerated without adverse reactions after topic and oral administration, respectively. Resistant viral strains have been found in cell culture in the presence of both drugs, but the frequency of resistance emergence during clinical use is unclear. To date, the biggest recognizable disadvantage of neuraminidase inhibitors and Amantadin/Rimantadin alike is that they need to be given within 30-48 h after onset of symptoms, but seeking medical attention at this stage of infection does not seem to be realistic in medical practice. As neuraminidase inhibitors up to now could mainly be assessed by experimental data, specifically performed clinical trials will have to prove the positive influence of these drugs on the morbidity, course of infection, and mortality of high risk persons when administered for prophylaxis as well as for therapy.
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Leitzke, S. (1999). Die Therapie der Influenza mit Neuraminidase-Inhibitoren. In: Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-38283-7_138
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DOI: https://doi.org/10.1007/978-3-662-38283-7_138
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