Aufhebung einer Morphin- induzierten Obstipation durch orales Naloxon

Zusammenfassung

Hintergrund: Häufigste Nebenwirkung einer Therapie chronischer Schmerzen mit Opioiden ist eine Obstipation. Sie beruht größtenteils auf einer Bindung der Opiode an Rezeptoren im Magen-Darmtrakt, aus der sie durch oral verabfolgtes Naloxon verdrängt werden können, ohne daß die analgetische Wirkung wegen der hohen präsystemischen Elimination des Naloxon aufgehoben wird.

Protokoll: In einem Therapieversuch erhielten 15 Patienten, die wegen chronischer Schmerzen mit Morphin behandelt wurden und obstipiert waren, Naloxon oral.

Ergebnisse: Zwölf Patienten hatten schon 1–4 h nach der ersten Gabe von Naloxon in einem Dosenverhältnis zu Morphin von 1:1 starken Stuhlgang, während drei Patienten auch nach wiederholter Naloxongabe nicht laxiert waren. Bei den laxierten Patienten konnte die Naloxondosis nach dem ersten Tag auf 2–15% der Morphindosis reduziert werden. Die Analgesie wurde durch orales Naloxon um 10–15% abgeschwächt, ließ sich jedoch durch Erhöhung der Morphindosis ohne erneute Obstipation wiederherstellen.

Abstract

Introduction: Almost all patients treated with opioids suffer from constipation. Numerous laxatives are used to overcome the problem, but none has yet been found to yield favourable results in all patients. Several studies have attempted to reverse opioid-induced constipation by the use of oral naloxone. Experiments carried out in rats showed that morphine-induced constipation is reduced by oral naloxone without impairment of antinociception [4]. However, evaluation of clinical studies reveals that there is uncertainty about the dosage regimen (the daily dose of naloxone ranged from 0.5% to about 60% that of morphine) and a lack of larger numbers of patients studied.

Methods: Fifteen patients suffering from opioid-induced constipation participated in the present study¹.

Results: Twelve patients experienced a strong laxative effect with spontaneous bowel evacuation 1 to 4 h after the first intake of oral naloxone. Three patients had no laxative effects even after repeated doses. Eleven of the 15 patients reported an average loss of 10%–15% of analgesia after oral naloxone as measured by visual analogue scales. Increasing the morphine dose by about 15% restored the previous level of analgesia without reappearance of constipation. Eight of the 12 patients having a laxative effect experienced abdominal cramps, and therefore, the total dose of naloxone was reduced on day 2 to 2%–15% of that originally planned; this dose still produced a laxative effect. Four of the 15 patients had a withdrawal syndrome. A single dose of morphine equivalent to their daily morphine intake abolished the symptoms.

Discussion: The medical history of the 3 patients in whom naloxone failed to abolish constipation revealed neurological disturbances. Treatment of these patients included the use of neuroleptics, antiemetics, and other drugs. In this context, it should be noted that oral naloxone can be expected to abolish only opioid-induced constipation. In conclusion, it was found that the treatment of opioid-induced constipation by administration of oral naloxone produced positive results. A controlled study will show, whether the side effects can be minimized by reducing the naloxone dose.