Alles beim Alten in der Pharmakotherapie von PONV?

Zusammenfassung

Eine neue Stoffklasse für die Prophylaxe von postoperativer Übelkeit und Erbrechen (PONV) sind Neurokinin1–Rezeptor–Antagonisten, die eine den herkömmlichen Antiemetika vergleichbare Wirkung gegen Übelkeit und leicht überlegene Wirkung gegen Erbrechen erzielen. Derzeit ist nur Aprepitant in oraler Applikationsform zugelassen. Palonosetron ist ein neuer Vertreter der Serotonin3–Rezeptor–Antagonisten ohne die erhoffte Überlegenheit am 2. und 3. postoperativen Tag, möglicherweise aber mit dem Vorteil der Nichtbeeinflussung des OT_c–Intervalls. Bei der PONV–Prophylaxe mit 5–HT₃–Rezeptor–Antagonisten sollten Interaktionen mit postoperativen Analgetika genauer beachtet werden. Niedrig dosiertes Droperidol kann weiterhin als Standardvertreter der Neuroleptika in der PONV–Prophylaxe gelten.

Abstract

Neurokinin–1 receptor antagonists represent a new approach in the prevention of postoperative nausea and vomiting (PONV) and show an efficacy comparable with those of common antiemetics with some evidence for superiority with regard to vomiting. Currently, only aprepitant is available as an oral preparation. Palonosetron is a new representative of the serotonin–3 receptor antagonists but without the hoped for superiority on the 2nd and 3rd postoperative days. However, available data do suggest that palanosetron does not prolong the OT_c interval. When using 5–HT₃–receptor antagonists for the prevention of PONV, anaesthetists should be aware of negative interactions with analgesics. Low–dose droperidol has regained approval and should be considered as first choice among the current available neuroleptics.

Schlüsselwörter:

Aprepitant - Palonosetron - Droperidol - postoperative Übelkeit und Erbrechen

Key words:

Aprepitant - Palonosetron - Droperidol - postoperative nausea and vomiting

Kernaussagen

• Neurokinin1–Rezeptor–Antagonisten erweitern das Spektrum der Antiemetika, indem sie zentral und peripher vermittelte emetogene Effekte der Substanz P aufheben.

• Derzeit einziger Vertreter der neuen Stoffklasse ist Aprepitant in oraler Applikationsform. Eine Weiterentwicklung zur intravenösen Gabe ist das Prodrug Fosaprepitant.

• In Phase II der klinischen Prüfung befinden sich Rolapitant und Casopitant. Sie sollen eine geringere Beeinflussung des CYP3A4–Metabolismus und eine über 48 h anhaltende klinische Wirkung aufweisen.

• Palonosetron ist ein neuer Vertreter der 5–HT₃–Antagonisten mit vergleichbarer Wirksamkeit ohne die erhoffte Überlegenheit am 2. und 3. postoperativen Tag.

• Granisetron weist einen CYP2D6–unabhängigen Metabolismus auf, sodass sogenannte „rapid metabolizer” eher von Granisetron als von anderen 5–HT₃–Antagonisten profitieren.

• 5–HT₃–Antagonisten weisen Interaktionen mit postoperativen Analgetika auf: Ondansetron verringert die Wirksamkeit von Tramadol, während Tropisetron und Granisetron eine paracetamolvermittelte Analgesie komplett aufheben können.

• Obwohl der klinische Einsatz der 5–HT₃–Antagonisten mit der „black box warning” der FDA zum Droperidol sprunghaft anstieg, ist auch diese Substanzklasse weitgehend mit einer Verlängerung des OT_c1Intervalls assoziiert.

• Niedrig dosiertes Droperidol ist in Deutschland seit Juni 2008 wieder zur PONV–Prophylaxe zugelassen. Die potenziell pro–arrhythmogene OT_c–Zeit–Verlängerung erfordert einen erhöhten Überwachungsaufwand, der bei Allgemeinanästhesien ohnehin Standard ist.

• 1–2 mg Haloperidol sind effektiv in der PONV–Prophylaxe – aufgrund häufigerer Nebenwirkungen jedoch kein adäquater Ersatz für Droperidol.

• Mit 25 mg Metoclopramid lässt sich dieselbe relative Risikoreduktion für PONV erreichen wie mit anderen Antiemetika. 10 mg sind in der Prophylaxe dagegen weder klinisch effektiv noch eine adäquate Vergleichssubstanz in PONV–Studien.

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