Opiatinduzierte Obstipation – Mechanismen, Relevanz und Behandlung

Zusammenfassung

Opiate hemmen die propulsive Motilität und Sekretion im Dünn- und Dickdarm. Das resultiert in abdominellem Völlegefühl, aufgetriebenem Bauch, seltenen harten Stühlen, die schwierig zu entleeren sind, und dem Gefühl der inkompletten Darmentleerung. Die Angaben über die Häufigkeit der opiatinduzierten Obstipation (OIO) schwanken erheblich, etwa die Hälfte der mit Opiaten behandelten Patienten leidet darunter. Das betrifft auch die transdermalen Systeme (Pflaster). Es wurden nur wenige klinische Studien mit Laxanzien bei OIO publiziert. An ihrer Wirksamkeit besteht zwar kein Zweifel, allerdings wirken sie nicht bei allen Patienten befriedigend. Ein anderer Ansatz besteht darin, die OIO mittels eines Opiatantagonisten zu behandeln bzw. zu verhindern. Dazu gibt es derzeit zwei Wege. Methylnaltrexon wirkt systemisch als Antagonist, kann aber die Blut-Hirn-Schranke nicht überwinden und ist nur in parenteraler Zubereitung erhältlich. Eine fixe Kombination aus Oxycodon und Naloxon im Verhältnis 2:1 kann dagegen oral gegeben werden, ohne den analgetischen Effekt systemisch zu antagonisieren. Durch den hohen first-pass-Metabolismus in der Leber wird Naloxon nämlich minimal systemisch verfügbar und antagonisiert das Opiat nur von luminal am Darm. Aufmerksamkeit gegenüber der OIO ist die Voraussetzung für eine optimale Schmerztherapie: Entweder man befragt den Patienten systematisch bzgl. OIO oder komediziert prophylaktisch.

Abstract

Opiates inhibit propulsive gastrointestinal motility and intestinal secretion in both the small and large intestine. The clinical result may be opiate induced constipation (OIC) presenting as one or more of the following symptoms: sense of abdominal fullness, bloated abdomen, infrequent stools, hard stools, difficult defecation, and sense of incomplete emptying of the bowel. The reported frequency of constipation on opioid treatment covers a wide range up to two thirds of patients. In fact, about one half of the patients seem to be affected. This applies also to transdermal systems. Only few trials have been conducted with laxatives in OIC. They work, but not satisfactorily in all patients. An alternative approach preventing or treating OIC is by co-administering an opiate antagonist. Methylnaltrexone is a systemically active antagonist poorly penetrating the brain and acting in the periphery only. It is available for subcutaneous administration only. A fixed combination of oxycodone with naloxone in a ratio of 2:1 can be administered orally and has also been proved to counteract or prevent constipation in patients without antagonizing pain relief. By its high first-pass metabolism in the liver naloxone does not reach systemically active serum levels and antagonizes the opiate only locally from the luminal side of the gut. A high awareness for OIC is mandatory for optimal pain management by either asking the patient for a treatment need or by prophylactically co-administering an opiate antagonist.

Schlüsselwörter

Opiate - Oxycodon - Methylnaltrexon - Naloxon - Obstipation

Keywords

opiates - oxycodone - methylnaltrexone - naloxone - constipation

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